philippine society of hypertension - the filipino doctor 1st ed hypertension.pdfphilippine society...

Philippine Society of HypertensionAffiliated with the International Society of Hypertension

and World Hypertension LeagueUnit 33,2/F, Facilities Centre, 548 Shaw Boulevard, Mandaluyong CityTel. Nos. 531-1204,531-1265; Fax No. (632) 531-1281

Officers and Board of Trustees 1997

PresidentVice-President

SecretaryTreasurer

Trustees

Ramon F. Abarquez, Jr., M.D.Yolando Q.M. Sulit, M.D.Gregorio B. Patacsil, Jr., M.D.Agnes D. Mejia, M.D.

Esperanza I. Cabral, M.D.Rody G. Sy, M.D.Nelson S. Abelardo, M.D.Francis M. Domingo, M.D.Mr. Gerry S. ArnedoMr. Elmer F. Deles

Multi-Sectoral Task Force on the Detection andManagement of Hypertension

Technical Research Committee

Antonio L. Dans, M.D.Bemadette A. Tumanan, M.D.Cristina R. Larracas, M.D.Felix Eduardo R. Punzalan, M.D.Eugenio B. Reyes, M.D.Luciene Lourdes C. Villacin, M.D.Maria Vanessa C. Villaruz, R.N.

Co-chair Co-chair

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Panelists

Ramon F. Abarquez, Jr. M.D.Ma. Lourdes E. AmarilloJoselito L. Atabug, M.DEliseo Banaynal, M.D.Annette P. Borromeo, M.D.Esperanza I. Cabral, M.DMa. Delta A. Canela, M.DEdeliza D. Carandang, M.D.Virgilio Castro, M.D.Jayvee G. Cruz, R.N.Antonio L. Dans, M.D.Liberty Fajutrao, M.D.Ms. Mayeth GoLeni Iboleon, M.D.Dean Artemio 0. IsidroRanulfo Javelosa, M.D.Anthony B. King, M.D.Cristina R. Larracas, M.D.

Agnes Mejia, M.D.Dante D. Morales, M.D.Oscar D. Naidas, M.D.Desiree M. Narvaez, M.D.Victoria Pacardo, M.D.Elizabeth Paz-Pacheco, M.D.Mayos Pe, M.D.Ms. Marisol L. PolicarpioFelix Eduardo R. Punzalan, Jr., M.D.Eugenio B. Reyes, M.D.Leonardo Rolle, M.D.Allan B. Ruales, M.D.Bernadette Tumanan, M.D.Ms. Felicidad V. VelandriaLuciene Lourdes C. Villacin, M.D.Maria Vanessa C. Villarruz, R.N.Amariles 0. Yazon, M.D.Ms. Clarissa G. Yu

Organizations Represented

Department of Health, Republic of the Philippines Fetus as a Patient Institute PhilippinesFood and Nutrition Research InstituteOccupational Safety and Health CenterPhilippine Obstetrics and Gynecology SocietyPhilippine College of Occupational MedicinePhilippine Diabetes AssociationPhilippine Heart AssociationPhilippine Lipid SocietyPhilippine Medical AssociationPhilippine Nurses AssociationPhilippine Society of HypertensionPhilippine Society of NephrologySports Medicine Association of the PhilippinesStroke Society of the PhilippinesPhilippine Society of OphthalmologyUniversity of the Philippines, College of Human KineticsU.P. College of Medicine, Clinical Epidemiology Unit and Cardiovascular SectionUniversity of the Philippines, College of Nursing

Funding Sources

Department of HealthNational Academy of Science and TechnologyPhilippine Council for Health Research and DevelopmentPhilippine College of PhysiciansPhilippine Society of HypertensionThesis grant to Bernadette A. Tumanan M D from PCHRD

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Plans and Programs of the Philippine Society of Hypertension

The Philippine Society of Hypertension (PSH) was incorporated on January 24,1994 and is affiliated with the International Society of Hypertension (ISH) and the World Hypertension League (WHL). Its vision is to control the hypertension epidemic. It is a multisectoral group composed of various medical, surgical and pedi-atric specialists as well as paramedical, pharmaceutical and lay professionals whose shared responsibility is the control of the hypertension epidemic.

Hypertension related mortality of 7/100,000 adults in the 80's has increased to 21/100,000 in the 90's, second only to Indonesia. The Philippines is third to Singapore in coronary artery disease and fourth to Japan in stroke mortality. These are statistics we do not intend to sur-pass. The treatment of hypertension is costly. In one industrial corporation, it amounted to 50% of total drug expenditures for its employees every year.

After an agenda setting workshop, existing hyperten-sive programs and data from varied other sources were collated. A knowledge attitude and practice survey was also conducted addressing the health providers and the clients. The data was presented during the first annual convention of the PSH. The updates and new concepts on hypertension control were presented by a faculty organized by Dr. Stevo Julius. This conference was simultaneously telecast to Cebu, Davao and Legaspi cities.

The next agenda is to "teach the teacher". A multi-sec-toral task force was convened for a formal consensus development program utilizing evidence based data systematically collated by a technical group from the Clinical Epidemiology Unit of the UP-PGH Department of Medicine. Funding was provided by the Department of Health (DOH), National Academy of Science and Technology (NAST), Philippine Council on Health Research and Development (PCHRD), Philippine College of Physician (PCP), and Philippine Society of Hypertension (PSH). The methodology was presented during the 2nd Annual Meeting of the PSH.

The 3rd Annual Meeting of the PSH was held in con-junction with the 2nd Pacific Rim Conference on Hy-pertension Control. This event was hosted and organized by the PSH and PCP and was held at the PICC last May 1997. There were over 150 foreign delegates represent-ing 23 countries and over 1,000 Filipino physicians who participated in the meeting. Over 25 foreign speakers participated in the scientific sessions. Highlights of this conference was the presentation of commonalities and differences in guidelines as well as hypertension control programs from different countries.

The PSH president presented the Paradigm Shift in Hypertension Control in a plenary session. From the 70's to the 90's, hypertension awareness, compliance and desirable BP control have improved by a mere 1% or 5% every 5 years. Althought the target adult population for hypertension control represents a minority, this is admittedly the productive sector of the country. Strate-gies beyond BP control that were discussed included 1) implications of genetic, gestational, and developmental characteristics as predictive factors for future hyper-tension; 2) risk multiplier implications of co-morbid factors in the development of adverse clinical events; 3) surrogate endpoints particularly LVH, microalbu-minuria, or congestive heart failure that occur and are modulated by factors independent of BP levels; 4) cur-rent anti-hypertensive agents that have reduced stroke by 29%, CAD by 14%, CHF by 49% (mostly) in the elderly, and LVH regression by 45%. These meta-analy-sis data suggest that a program is needed to motivate the non- hypertensive population to submit to regular BP check-ups and apply lifestyle modifications. More importantly, BP management should include strategies beyond BP control.

On-going agenda for health providers includes the dis-semination of the practice guidelines on hypertension management and evaluation of the impact of the practice guidelines on the actual practice of physicians. Programs for the public will include self BP monitoring and as-sessment of cardiovascular disease risk factors as well as lifestyle modification particularly related to smoking, obesity and physical inactivity.

Our expectation therefore, on a short-term basis, is to increase the awareness of the hypertension problem and its implications, to implement routine BP monitoring for children and adults who are at risk for hypertension and to carry out co-morbid risk management with the hypertensive patients. On a long-term basis, reduction of hospitalization and death related for CHF, CVA, CAD and renal failure are to be expected.


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Foreword

The Philippine Society of Hypertension Inc. (PSH), affiliated with the International Society of Hypertension (ISH) and the World Hypertension League (WHL), has a multi-sectoral individual and corporate membership. Its vision is the control of the hypertension epidemic. Its mission is to "teach the teacher" by evolving together"shared responsibilities" in the development of programs and strategies.

This "Clinical Practice Guidelines in the Detection & Management of Hypertension" is the output of a Multi-Sectoral Task Force representing 20 organizations among the panelists and at least 50 organizations in the public forum. Major contributors to the grant-in-aids are the National Academy of Science and Technol-ogy (NAST), Department of Health (DOH), Philip-pine Council for Health Research and Development (PCHRD), Philippine College of Physicians (PCP), and the Philippine Society of Hypertension (PSH).

The special features of the guidelines are:

1) A multi-sectoral formal consensus development methodology;

2) Specified levels of evidence-based documentation for each recommendation given;

3) Risk stratification of hypertensives in relation to target organ involvement and co-morbid events;

4) Emphasis on local problems like pregnancy-related hypertensive problems, role of herbal and non-tra-ditional approaches and;

5) Emphasis on primordial preventive measures.

The recommendations given are based on the assumptions that:

1) Patients to be treated meet the inclusion criteria of the various studies used in the evidence-based guidelines;

2) Local clinical endpoints approximate the extrapo-lated morbid and mortality prevalences used in the study populations;

3) Health providers will avail of the voluminous refer-ences cited;

4) Sound clinical judgement should prevail since the attending physician has more information available to him than what the guidelines can supply.

PSH recognizes that about 12% of the adult popula-tion or 4.2 million Filipinos have hypertension. Only 50 % of this group are aware of the problem, among those who are being treated, only about 50% are getting advice and treatment. However, only about 25% will have acceptable BP control. Thus, 3.6 million adults can benefit from monitored management. This number

represents a considerable proportion of the productive sector of the country.

The Board of Trustees of the Philippine Society of Hy-pertension & all those who contributed to the realization of the Guidelines express their sincere appreciation to all who join us in our efforts to control the hypertension epidemic in our country.

The Philippine Society of HypertensionOfficers and Board of Trustees

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The recommendations contained in this CLINICAL PRACTICE GUIDELINES are intended to GUIDE practitioners in the detection and management of hypertension in adult patients. In no way should the guidelines be regarded as absolute rules, since nuances and peculiarities in individual cases or particular communities may entail differences in the specific approach. In the end, the recommendations should supplement, and not replace sound clinical judgement.


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The Philippine Clinical Practice Guidelines on the Detection and Management of Hypertension

Report of the Multisectoral Task Force on the Detection and Managementof Hypertension Convened by the Philippine Society of Hypertension

Introduction

The multi-sectoral task force for the Control of Hy-pertension was convened by the Philippine Society of Hypertension. During the agenda-setting conference held on August 12, 1995 at the Development Academy of the Philippines, Pasig City, the need for local guide-lines on the detection and management of hypertension was identified. The multi-sectoral task force was thus formed to address this need. Thirty-six (36) participants representing 20 governmental & non-governmental organizations participated in the guideline develop-ment process, which took place in 4 phases, outlined as follows:

Phase 1 - Preparation of the Evidence Based Report (EBR).

This initial draft of the manuscript was prepared by a Technical Research Commit-tee whose members tracked, retrieved, and appraised current evidence pertaining to the detection and management of hyperten-sion.

Phase 2 - Preparation of the Intermediate Report. The 2nd draft of the manuscript was prepared

by all members of the multi-sectoral task force, based on their criticism and appraisal of the initial EBR. This was achieved in a 2-day meeting which was held at Corregidor from January 12-14 1996. A consensus was defined as 75% of votes cast during any circulation.

Phase 3 - Preparation of the Penultimate Report. The 3rd draft was prepared after 3 circu-

lations of intermediate versions by mail (modified Delphi technique), with panelists requested to vote and comment on specific statements, until a consensus was reached on the various issues raised.

Phase 4 - Preparation of the Final Report. The final draft was prepared after consid-

eration of the comments and feedback of non-panelists. These non-panelists included representatives of pharmaceutical compa-nies, heads of related societies, and other educational influentials.

The following 6 questions are addressed by the present guidelines:

A. How should blood pressure be measured?B. How should hypertension be diagnosed?C. How should hypertension be worked up?D. What advice should hypertensive patients receive

regarding lifestyle modifications?E. How should hypertension be treated?F. How can hypertension be prevented among normo-

tensives?

Assessment of Evidence from the Medical Literature:

Evidence addressing these 6 problems were classi-fied according to a system adopted by the Canadian Hypertension Society [1]. This system allows rating of studies on a scale of 1 to 6 (best to worst, respectively), using standardized criteria to assess methodologic rig-our (see appendix). Recommendations throughout the guidelines are then graded from A to D depending on the best evidence that supports them (Table 1). Thus, grade A recommendations are based on the strongest evidence from properly conducted randomized control-led trials. On the other hand. Grade D recommendations are based on weaker study designs including expert's opinions, clinical experience and common sense. Grade D recommendations often address practical issues of implementation and other factors existing in the local setting which are not addressed in clinical trials.

Table 1. Grading system for recommendations

Grade A The recommendation is based on one or more studies at level 1.

Grade B The best evidence available is at level 2.Grade C The best evidence is at level 3.Grade D The best evidence available is lower than

level 3, and included expert's opinions, clinical experience and common sense. These recommendations address practical issues of implementation and other factors existing in the local setting.

Recommendations

A. HOW SHOULD BLOOD PRESSURE BE MEASURED?

1. The most accurate and reliable technique for

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indirect blood pressure measurement is the auscultatory method using a mercury manom-eter (Grade A Recommendation).

Summary of Evidence: Previous technical pub-lications[2,3] and consensus statements [4-6] have adequately described the technique of indirect blood pressure measurement using the auscultatory method. The method described in Table 2 highlights technical requirements which are common to these statements.

Table 2. Methods for Indirect Measurement of Blood Pressure

1. A mercury manometer is ideal for accurate measurement. Aneroid, digital or other auto-mated devices provide reasonable alternatives, provided that they satisfy technical requirements for accuracy, and are calibrated and tested on a regular basis.

2. The manometer cuff should cover at least 2/3 of the length of the patient's arm, while the bladder should cover at least 80% of the arm circumference.

3. The patient should be seated (or supine) with arms bared, supported, and at heart level. They should have rested for at least 5 minutes, and should not have smoked or ingested caffeine within 30 minutes before measurement.

4. The edge of the cuff should be placed 1 inch above the elbow crease, with the bladder directly over the brachial artery.

5. The bladder should be inflated to 30 mmHg above the point of radial pulse extinction as determined by a preliminary palpatory deter-mination. It should then be deflated at a rate of 2 mmHg/beat, with the stethoscope bell placed directly over the brachial artery.

6. Systolic pressure should be recorded at the appearance of the 1st clear tapping sound (Korotkoff phase 1). Diastolic blood pressure should be recorded as disappearance of these sounds (Korotkoff phase V), unless these are still present near 0 mmHg in which case, softening of the sounds should be used as diastolic pressure (Korotkoff phase IV).

7. For every visit, the mean of 2 readings, taken at least 2 mins apart, should be regarded as the patient's blood pressure. If the first 2 readings differ by 5 mmHg or more, a third reading should be included in the average.

8. If blood pressure is being taken for the first time, the procedure should be repeated with the other arm. Subsequent determinations should then be performed on the arm with a higher pressure reading.

2. In the absence of a mercury manometer, aner-oid, digital and other self-monitoring devices may provide acceptable alternatives, provided they have passed technical requirements for accuracy, and are calibrated or checked regu-larly (Grade D Recommendation).

Summary of Evidence: Economical self-monitoring devices have flooded the market. Although some doubt has been raised regarding their accuracy [7}, these instruments may provide the only options for screening and follow-up in many situations.

B. HOW SHOULD HYPERTENSION BE DIAG-NOSED?

1. Strategies for Detection

a. Case Finding - Opportunities for case-finding abound in daily practice. Health practition-ers from all fields should be encouraged to take BP measurements at each patient visit if the patient consults for unrelated symptoms (Grade A Recommendation).

b. Mass Screening - In developing countries, many individuals have limited access to health care. Consequently, hypertension cannot be detected by the method of case-finding. In such situations, an alternative may be mass screening programs, where health care pro-viders conduct household visits to measure blood pressure. Such programs may be justi-fied, as long as diagnosis can be confirmed & treatment is provided (Grade D Recommen-dation).

Summary a/Evidence: The validity of recommen-dations to detect for hypertension finds support in largescale randomized clinical trials which demon-strate that subsequent treatment leads to a reduction in vascular events [8]. In addition, cost-effectiveness studies have shown that the benefits achieved from screening asymptomatic adults for hypertension outweighs the risks & costs [9,10].

2. Strategies for Confirmation

The diagnosis of hypertension should be based on repeated measurements (at least 2 visits) showing sustained elevation. It should not be based on single determination (Grade A Recommendation). A proposed schedule for confirmation based on initial BP readings is summarized in Table 3 [4]. This schedule is based on recommendations of the fifth report of the Joint National Committee on Hyperten-


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sion (JNC V) (Grade D Recommendation).

Summary of Evidence: Variability in blood pressure determination has been well-documented [11-17]. This variability stems from several factors which include a) natural fluctuation or variability and b) variation brought about by the technique of blood pressure determination. The latter source of vari-ability can be minimized by use of proper technique as described in Table 2. Natural variability, on the other hand, is best handled by repeated measure-ments, that is, through a confirmation schedule.

Table 3. Recommended confirmation schedule for hypertension based on initial levels of blood pressure.q

Initial level of BP Recommended confirmation in mmHg* schedulef systolic diastolic <130 <85 Recheck in 2 years 130-139 85-89 Recheck in 1 year 140-159 90-99 Confirm in 2 months 160-179 100-109 Evaluate or refer to source of care within 1 month 180-209 110-119 Evaluate or refer to source of care within 1 week ≥210 ≥120 Evaluate or refer to source of care immediately

q These recommendations hold for patients who are not presently on treatment for hypertension. If doubt exists regarding the diagnosis in patients already on treatment, drugs may be stopped for an appropriate period before commencing with a confirmation schedule.

* If systolic and diastolic categories are different, follow recommendations for the higher level.

f Scheduling of follow-up should be modified by reliable information on past BP measurements, seventy of target organ damage, and presence of other risk factors.

Definition

• Hypertension is defined as sustained systolic BF elevation of 140 mmHg or more, OR sustained di-astolic BP elevation of 90 mmHg or more, based on measurements done during at least 2 visits taken at least 1 week apart (Grade A Recommendation).

• Patients with intermittent elevation in blood pres-sure should not be labeled as hypertensives. An example would be "white-coat" hypertension, which is defined as BF elevation in the clinic setting but repeatedly normal out of the office (Grade A Recommendation).

• Isolated systolic hypertension is defined as systolic blood pressure of 140 mmHg or more and a di-astolic pressure of less than 90 mmHg (Grade B Recommendation).

Summary of Evidence: The advocated definition of hypertension is "therapeutic" in nature [18], in that it identifies a population that can benefit from sub-sequent therapy. Studies have shown that medical treatment decreases the incidence of cardiovascular events, when administered to patients with diastolic blood pressure of 160 mmHg or more [19-23]. A lower systolic level of 140 mmHg was accepted by the panelists, although only 1 RCT used such a cut-off [24]. This was deemed necessary in order to adhere with internationally accepted standards [4,6].

Classification

Hypertensive individuals should be classified accord-ing to severity of blood pressure, target organ dam-age, and presence of other risk factors. The system of classification recommended by JNC V is summarized in Tables 4, 5 and 6 (Grade D Recommendation).

Summary of Evidence: Severity of hypertension is a major determinant of the probability of developing a vascular event in the future [25]. Thus, clinical clas-sification of severity may have important implications on urgency of treatment, the choice of drugs, the number of medications given initially, and the frequency of fol-low-up. Further refinement by classification according to target organ damage provides an idea of disease chronic-ity as well as severity, and gives an insight on the stage of disease progression. Final clarification by inclusion of other risk factors in the final classification furnishes a master plan for subsequent management. Tables 5 and 6 list the risk factors for coronary artery disease and manifestations of target organ damage by hypertension.

Table 4. Classification of Blood Pressure forAdults Aged 18 years or older *

Mean BP in mmHgf Classificationq

systolic diastolic <130 <85 Normal 130-139 85-89 High normal 140-159 90-99 Stage 1 (Mild) 160-179 100-109 Stage 2 (Moderate) 180-209 110-119 Stage 3 (Severe) ≥210 ≥120 Stage 4 (Very severe)

* This classification holds true for patients who are not acutely ill and are not currently taking antihypertensive medications.

f Classification should be based on the average of two or more readings taken at each of 2 or more visits after an initial screening. If systolic and diastolic categories are different, follow recommendations for the higher level.

q In addition to classification based on severity, patients should be classified according to the presence or absence of target organ damage and additional risk factors. Thus, a patient with diabetes and a BP of 142/94 mmHg plus left ventricular hypertrophy should be classified as having "stage 1" hypertension with target organ disease (LVH) and with another major risk factor (diabetes).

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Table 5. Risk factors for Coronary Artery Disease

Modifiable risk Non-modifiable risk factors factorsSmoking AgeHypertension Male sexDyslipidemia Family history of premature CADDiabetes MellitusObesityPhysical inactivity

Table 6. Manifestations of Target-Organ Disease Organ system

Organ System ManifestationsCardiac Clinical, electrocardiographic or radiologic evidence of coronary artery disease Left ventricular hypertrophy by electrocardiography or cardiac failureCerebrovascular Transient ischemic attack or strokePeripheral Absence of one or more majorVascular pulses in the extremities (except in the dorsalis pedis) with or without intermittent claudication; arterial aneurysms.Renal Serum creatinine ≥130 mmol/L (1.5 mg/dL) Proteinuria (1 + or greater)Retinopathy Retinal arteriolar attenuation; Hemorrhages &/or exudates, with or without papilledema/ optic nerve edema

Source: The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1995; 153; 154-183.

Diagnosis

C. HOW SHOULD HYPERTENSION BE WORKED UP ?

The objectives of a thorough hypertension work-up include the following:a) To determine the etiology of hypertension,b) To determine the extent of target organ damage,c) To detect (and possibly treat) other risk factors for

cardiovascular disease, andd) To determine if there are contraindications to the use

of certain drugs.

With these objectives in mind, physicians should pay close attention to all aspects of the clinical evaluation, including extraction of a detailed history, performance of a thorough physical examination, and requisition of relevant laboratory tests.

1. A detailed history and physical examination should be done in all patients with hypertension (Grade A Recommendation). Aspects of the his-tory and PE which should be emphasized are summarized in Table 7.

Summary of Evidence: Effectiveness of treatments used in randomized controlled trials depends on du-plication of the quality of care which was rendered during the trial period. The medical history and physical examination were carefully conducted in hypertension trials in order to search for other risk factors, evidence of target organ damage, evidence of secondary hypertension, and possible contrain-dications to use of certain drugs [23-30]. This quality of care thus becomes imperative, in order to maximize the benefits of treatment.

Table 7. Items to emphasize in the clinical history and physical examination of hypertensive patients.

CLINICAL HISTORY

1. Previous symptoms of cardiovascular, cerebrov-ascular, pulmonary, or renal disease, diabetes mellitus, gout, or dyslipidemia;

2. Family history of hypertension, premature car-diovascular death, stroke, diabetes mellitus, or dyslipidemia;

3. Personal and social history of smoking or tobacco use, occupational or domestic stress;

4. Usual BP range with and without medication;5. Medications tried for hypertension, including

response and adverse effects;6. Other medications being taken which may affect

BP or response to treatment (e.g. contraceptives, steroids, NSAIDs, decongestants, appetite sup-pressants, cyclosporin, erythropoietin, TCAs, and MAO-inhibitors.

PHYSICAL EXAMINATION

1. Height and weight measurement;2. Head and Neck - funduscopic examination, ex-

amination of the neck for bruits, distended veins or thyroid enlargement;

3. Chest and Lungs - examination of the heart for in-creased heart rate, increased size, heaves, clicks, murmurs, arrhythmias, gallops; examination of the lungs for wheezing and other signs of chronic lung disease;

4. Abdomen - examination of the abdomen for trun-cal obesity, purple striae, bruits, enlarged kidneys, masses, and abnormal aortic pulsation;

5. Examination of the extremities for diminished or absent peripheral arterial pulsations, bruits, and edema; arm blood pressure discrepancies greater than 10 mmHg, or when indicated, similar discrepancies between leg blood pressures; ex-amination of presence of postural hypotension in the elderly, i.e., decrease in blood pressure greater than 10 mmHg on assumption of upright position from recumbent position.

6. Neurologic assessment for stroke residuals or encephalopathy.


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2. The following tests should be routinely performed in newly diagnosed hypertensives (Grade A Recommendation):

a. fasting plasma glucose b. serum creatinine, c. serum potassium, and d. urinalysis

Summary of Evidence: All the tests listed above were used in various trials to screen for conditions which, even in their asymptomatic phase, have an effect on the choice of antihypertensive medication [4]. Ad-ditional benefits include a) detection and early treat-ment of diabetes with a screening FPG, b) detection of asymptomatic renal disease with a serum creatinine and urinalysis and, c) detection of possible secondary hypertension with a serum potassium.

3. The following examinations may be performed only if there are specific indications (Grade D Recommendation):

a. ECG b. chest X-ray c. determination of lipid profile d. uric acid e. hematocrit

Summary of Evidence: Because of a very low sensitivity and specificity in the detection of myocardial ischemia [31], the usefulness of a resting 12-lead ECG is limited in asymptomatic patients. On the other hand, when symptoms of ischemia are present (e.g. in the pres-ence of chronic stable angina pectoris), the test may be useful as a screening test for severe disease, usually manifested by resting ST segment depression. Other uses of the ECG include the detection or clarification of dysthymias as well as detection of LVH. For the lat-ter, its usefulness is limited by high false positive and negative rates [32,33]. Chest X-ray may contribute to the detection of hypertrophy but again it is limited by its low sensitivity and specificity The other examinations - uric acid, hematocrit and total cholesterol can be requested if there are clinical features suggesting that these may be elevated. Specific indications for determination of lipid profile, are addressed by the multisectoral task force on the detection and management of hypercho-lesterolemia [34].

4. 2D echocardiography is not required for the routine evaluation of all hypertensive patients (Grade D Recommendation). Use should be restricted to patients in whom anatomic or func-tional abnormalities are suspected.

Summary of Evidence: The echocardiogram is more

sensitive than both the ECG and chest radiogram in the detection of left ventricular hypertrophy [35]. Although studies suggest that some drugs are more effective than others in effecting regression of LVH [36,37], there is no evidence yet that such an effect leads to a reduction in mortality or cardiovascular events.

5. Ambulatory BP monitoring is not routinely required for the work-up of all hypertensive patients (Grade D Recommendation).

Summary of Evidence: The clinical utility of ambulatory BP monitoring has been well-summarized in various documents [7,38]. Major problems need to be resolved before they become more widely used. These problems include: 1) evaluation of accuracy and precision of vari-ous monitoring devices, 2) definition of hypertension based on 24-hour results, and 3) evaluation of cost-ef-fectiveness compared to standard office measurement.

6. Confirmatory tests for secondary hypertension should be performed only when clinical clues to their existence are present (Grade D Recom-mendation). Physical findings which should lead to the suspicion of these rare conditions are sum-marized in Table 8.

Summary of Evidence: When the pre-test probability of a condition is extremely low (i.e., when the condition is very rare), tests that detect it, need to be extremely sensi-tive to be of any use [39]. This principle holds true in the case of testing for secondary hypertension. Routine conduct of such tests is of little use, because the conditio ns are rare. On the other hand, when clinical clues are present, the probability of some conditions increase, thus allowing maximization of the operating characteristics of the diagnostic tests. Physicians unfamiliar with such tests should refer patients with suspected secondary hypertension to specialists for further work-up.

Table 8. Clinical clues to secondary causes of hypertension

CLINICAL CLUES

SUSPECTED CONDITIONabdominal or flank masses, family polycystichistory of adult polycystic kidney kidneyabdominal bruits, especially if a renovascular diastolic component is present diseasedelayed or absent femoral pulses, aorticor decreased BP in the lower coarctationextremities truncal obesity w/purple striae Cushing's syndrometachycardia, tremor, orthotastic pheochromohypotension, sweating, flushing cytoma

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and pallor anemia, edema, azotemia, casts Chronic renal diseasepulse discrepancy Takayasu's arteritiscramps, body malaise, Hyper-hypokalemia aldosteronismuse of contraceptive pills Contraceptive- induced HPNneck mass w/ bruit, lid lag with Thyrotoxicosisor without exophthalmospoor BP control w/ drug therapy any of the abovesudden onset of hypertension any of the abovesudden deterioration of BP any of the abovecontrol

Precautions

D. WHAT ADVICE SHOULD BE GIVEN TO HYPERTENSIVE PATIENTS REGARDING LIFESTYLE MODIFICATIONS?

1. All smokers should stop smoking (Grade A Rec-ommendation).

Summary of Evidence: Several cohort and case-control studies provide unquestionable proof of the hazards of smoking [40], As a recognized risk factor for the deve-lopment of coronary artery disease, smoking aggravates this risk in a hypertensive patient.

2. a. Overweight patients (excess of > 10% of ideal body weight) should attempt weight reduction at a rate of 1.0 Ib or 0.5 Kg per week (Grade B Recommendation).

b. Weight reduction can be achieved by caloric reduction and regular in aerobic activities (see item 3). Caloric reduction can be achieved through dietary prescriptions from a nutri-tionist. However, in the absence of a profes-sional nutritionist, patients can be advised to decrease their saturated fat intake to 15% or less of their total caloric intake (Grade D Recommendation).

Summary of Evidence: No trials have shown that weight reduction actually translates to a decrease in cardiovascular events. Nevertheless, weight reduction in overweight hypertensive patients can lead to sub-stantial declines in blood pressure, and can enhance the blood pressure-lowering effect of antihypertensive agents [41-42].

3. Hypertensive patients should engage in regular aerobic physical activity unless contraindi-cated (Grade A Recommendation). This may

be achieved by lower extremity aerobic exercise such as brisk walking, jogging, or cycling for 30-60 minutes 3-4 times per week.

Summary of Evidence: Regular aerobic physical activity can reduce blood pressure in hypertensive patients [43]. In addition, it facilitates weight reduction, improves functional status, and leads to a decrease in CVD and all-cause mortality [43]. These gains are attained even at moderate levels representing 40-60% of maximum oxygen consumption. Thus, an exercise program need not be expensive or complicated. Brisk walking for 30-60 mins three to 4 x a week is simple and attainable by most patients. However, patients with suspected or confirmed cardiovascular disease may need a thorough evaluation before exercise is prescribed.

4. Alcohol drinkers should moderate their consump-tion. A reasonable limit would be 30 cc (1 oz or 28 grams) of ethanol per day (equivalent to 60 cc or 2 jiggers of 100-proof whiskey, 240 cc or 1 glass of wine, or 720 cc or 2 bottles of beer) (Grade D Recommedation).

Summary of Evidence: Excessive alcohol intake can lead to blood pressure elevation and resistance to antihyper-tensive therapy [44]. Table 5 (See Appendix) gives the alcohol content of common alcoholic drinks.

5. Moderation of dietary sodium to 100 mmol/day (2.3 g Na, 6 g NaCI) may be attempted in all hypertensive subjects to see if this can lead to significant BP reduction (Grade B Recommen-dation). However, such restriction is absolutely necessary among patients with Chronic Renal Disease & Congestive Heart Failure (Grade D Recommendation).

Summary of Evidence: Considerable controversy exists regarding the usefulness of sodium restriction among all hypertensive patients [44]. While trials have shown that it can lead to appreciable declines in mean blood pressure [45,46], such declines are experienced by only 25 to 33% of subjects (salt-sensitive individuals). Generalizing these results to all hypertensives, where salt consumption is relatively high, can lead to major problems in quality of life. Moreover, no trial has demonstrated that salt reduction can lead to a decline in cardiovascular events.

6. There are no good studies to justify recommenda-tions regarding relaxation and biofeedback nor an increase in dietary K, Ca, or Mg.

Summary of Evidence: Recent meta-analysis on relaxa-tion and feedback showed that these non-pharmacologic measures were not successful in decreasing blood pres-


42

sure [47]. The same finding were also seen in interven-tions involving dietary K, Ca, or Mg content [48].

Treatment

E. HOW SHOULD HYPERTENSION BE TREATED?

The goal of treatment is to normalize blood pressure. The following recommendations suggest priority therapeutic options, depending on the underlying circumstances. When contraindications exist for these options, or when they fail to control hypertension, other drugs may be tried (see Table 6 of Appendix for list of drugs).

Another consideration which may affect drug selection is patient compliance. In some situations, this may take precedence over the given recommendations. When this becomes a problem, maneuvers to improve compli-ance may take into consideration 1) the drug's dosing schedule, 2) cost, 3) side effects or 4) an individual's preference for a particular regimen.

Lastly, patient's education must include the need for maintenance medications despite normalization of blood pressure as well as regular follow-ups.

1. Uncomplicated Hypertension

a. In uncomplicated mild hypertension (Stage I), lifestyle modification measures may be attempted for 3 months before commencing pharmacologic treatment (Grade D Recom-mendation).

Summary of Evidence: The TOMH study showed that pharmacologic treatment and lifestyle modification was superior to lifestyle modification alone [23]. The 4-year incidence of death or vascular events in the treatment group was 11.08% compared to 16.24% in the group that received lifestyle modification alone (p=0.03). Thus events were prevented in 5.6% of patients, that is, 1 of every 20 who were treated. Nevertheless, a 3- month trial of lifestyle modification alone was advocated by the consensus panelists, since previous studies have demonstrated that normalization of mild hypertension can occur, even without pharmacological intervention [50].

b. All classes of antihypertensive agents (Table 6, Appendix) have been shown to lower blood pressure with varying degrees of effectiveness and side effects. However, in uncomplicated hypertension, unless contraindications ex-ist for their use, ß-blockers or diuretics are recommended as the initial agents for mono-therapy (Grade A Recommendation).

Summary of Evidence: This recommendation is based on the results of several overviews and meta-analysis which showsignificant reduction in stroke and coronary artery disease with the use of diuretics (chlorthalidone, or thiazides) or ß- blockers [1, 4, 5, 8, 50-52]. On the other hand, the dreaded side effects of diuretic use, that of cardiac dysrhythmias associated with hypokalemia & low levels of serum magnesium were seen in sub-group analyses of studies which use high doses of diuretics in combination with other drugs with negative inotropic effects. These results were not duplicated when the sa me type of sub-group analysis was done on the Hy-pertension Detection & Follow-up Program (HDFP) [50]. In addition, these 2 classes of drugs are the most economical agents in the market. Their use has been shown to profoundly improve the cost-effectiveness of CAD & CVD prevention [9, 52-54].

Although other agents have also been found to decrease blood pressure, no long-term studies assessing their effects on clinical end-points such as strokes, coronary events or mortality were done. TOMHS evaluted the use of an ACE-inhibitor, alpha-blocker, fi-blocker, Ca antagonist or diuretic in mild hypertension. However, as a consequence of the size & duration of follow-up of TOMHS, there was inadequate power for comparing drug treatments with one another for efficacy in prevent-ing cardiovascular events [23].

2. Hypertension complicated by Ischemic Heart Disease.

a. In patients with ischemic heart disease, fi-blockers or ACE-inhibitors are the drugs of choice depending on the clinical presen-tation (Grade A Recommendation). Cer-tain calcium antagonists provide reason-able alternatives but short-acting nifed-ipine should be avoided. Specific recom-mendations are summarized in Table 9.

Table 9. Choices for initial monotherapy of hypertension in patients with various ischemic syndromes.

CONDITION DRUG OF ALTERNATIVE CHOICE* DRUGS1. Q wave BETA-BLOCKERS VERAPAMIL**

acute MI and ACE-inhibitors (Grade A)2. NON-Q wave BETA-BLOCKERS DILTIAZEM**

acute MI & ACE-inhibitors (Grade A)3. UNSTABLE BETA-BLOCKERS No specific ANGINA (Grade A) recommendations***

4. STABLE BETA-BLOCKERS No specific ANGINA (Grade A) recommendations* * *

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CPM 1ST EDITION

* In secondary prevention trials (patients with stable and unstable angina and acute myocardial infarction), the use of fi-blockers resulted in a reduction in morbidity and mortality. ACE-inhibitors, on the other hand have also been shown to decrease mortality in patients with acute myocardial infarction 159].

** In post-MI patients in whom fi-blockers or ACE-inhibitors are contraindicated, verapamil 160] or diltiazem may be used. This is based from the results of a trial using verapamil which showed reduction of coronary events and total mortality in patients after Q infarction. The use of diltiazem in non-Q infarction 161], on the other hand, resulted to a decrease in reinfarction rate although mortality was not reduced. Benefits from either verapamil or diltiazem are seen only in post-Mi patients without heart failure.

*** No specific recommendations are given for alternative drugs for unstable and stable angina except for the non-use of nifedipine. This is based on the present controversy with regards its use on patients with ischemic syndromes (see next item).

b. In patients with ischemic syndromes, short-acting nifedipine should be used with caution (Grade B Recommendation).

Summary of Evidence: A meta-analysis by Furberg [63] showed increased mortality in patients with coronary heart disease (stable and unstable angina and acute myocardial infarction) who were given nifedipine. It is in this regard that questions were raised on its use in such patients [64-66]. Because of some methodologic flaws of this meta-analysis, its validity was doubted [67-69]. Furthermore, ill effects were said to be statistically significant only with the use of higher doses, i.e., >80 mg/day. In view of this, Opie & Messerii re-analyzed the data, and still, the possibility of harm i.e., increase in mortality, could not be eliminated [66]. The relative risk (RR) with regards the use of 30-60 mg/day was 1.1 with the 95% confidence interval ranging from 0.95 to 1.27 (effect ranging from a 5% reduction in mortality to a 27% increase in mortality). When all studies were combined, Messerli's recalculation showed a trend towards increased mortality, p=0.07 [70].

3. Hypertension complicated by Congestive Heart Failure

a. In the setting of congestive heart failure, hypertensive patients may receive ACE-in-hibitors with or without diuretics (Grade A Recommendation).

Summary of Evidence: ACE-inhibitors are indicated in patients with congestive heart failure even without hy-pertension. This is supported by numerous randomized controlled trials showing reductions in total mortality as well as coronary events [71-73].

b. When the use of ACE-inihibitors are con-traindicated, a combination of isosorbide

dinitrate and hydralazine may be used (Grade A Recommendation).

Summary of Evidence: The first V-Heft trial showed that the combination of isosorbide dinitrate and hydralazine was better than placebo in patients with mild to moderate congestive heart failure treated with digoxin and diuret-ics [74]. The V-Heft II trial however, showed superiority of the ACE-inhibitors over this combination [73]. The use of a 3rd-generation Ca antagonist, Amiodipine as an alternative based on a recent study could not be advocated because of the following reasons: 1) improve-ment in functional capacity was seen only in a subgroup analysis - group of patients with cardiomyopathy; 2) no significant reduction in mortality was found, thus one cannot eliminate harm, and 3) the study is not yet pub-lished, thus peer-review has not been completed.

4. Hypertension complicated by Diabetes Mellitus

a. In hypertensive diabetic patients with good glycemic control, ß-blockers and diuretics are the preferred antihypertensive agents (Grade A Recommendation).

Summary of Evidence: Diabetic patients were included in the trials, using fi-blockers and diuretics which showed decreased in mortality rates, stroke and coronary artery disease. These studies were the First Veterans Administration Study, (VA I), Oslo Study, International Prospective Primary Prevention Study in Hypertension (IPPSH), Metoprolol Atherosclerosis Prevention in Hy-pertension Study (MAPHY), European Working Party on High Blood Pressure in the Elderly Trial (EWPHE), Systolic Hypertension in Elderly Program (SHEP), & the Swedish Trial in Old Patients with Hypertension (STOP) [22, 27, 50, 75]. The overall increase in fasting blood glucose during the follow-up period, (2-5 years) was 0.2 to 0.6 mmol/L. In another study by Lewis [76] on insulin-dependent diabetics, ß-blockers and diuretics were also the principal agents used to control hyperten-sion. ACE-inhibitors were added to address the problem of proteinuria [76].

b. In hypertensive diabetic patients with poor gly-cemic control, ß-blockers and diuretics should be avoided (Grade A Recommendation).

Summary of Evidence: In stated trials using fi-block-ers and diuretics, patients with uncontrolled diabetes mellitus were excluded, because of the dangers of 1) worsening glycemic control and 2) the possibility of masking hypoglycemia.

c. In hypertensive insulin-dependent diabetics with urinary excretion of 500 mg/24 hours or more and a serum creatinine of 2.5 mg/dL


44

or less, the addition of ACE-inhibitors to the regimen, particularly captopril, can lead to additional benefits - i.e. decrease in mortal-ity rate, need for dialysis or transplantation (Grade A Recommendation).

Summary of Evidence: This statement is based on randomized controlled trial by Lewis et. al. [76] on insulin-dependent diabetics. Included in the study were patients who are 18-49 years old who had IDDM for at least 7 years with an onset before the age of 30 years and with urinary protein excretion of 500 mg/24 hours or more and a serum creatinine or 2.5 mg/dL or less. It was shown that the addition of captopril at 25 mg TID to existing anti-hypertensive medication resulted in a 48% relative risk reduction or a 10% absolute risk reduction in the combined endpoints of death, or need for dialysis, or transplantation. This means that for every 10 patients treated, 1 event will be avoided. Moreover, it also led to a 43% relative risk reduction in the risk of doubling of serum creatinine. It must be noted that in this trial, captopril was not given as the drug to control hypertension. It was given to treat proteinuria. Seventy-five percent of the patients, both from the control as well as the treatment group were receiving diuretics or ß-blockers before the study and their usage even increased further during the study period. The median follow-up of patients was 3 years.

d. In non-insulin dependent diabetics, ACE-in-hibitors (especially captopril and enalapril) may be used to decrease proteinuria or improve glomerular filtration rate (Grade B Recommendation); if ACE-inhibitors are contraindicated, nondihydropyridine Ca an-tagonists (especially verapamil and diltiazem) may be used as alternative agents (Grade B Recommendation).

Summary of Evidence: A meta-analysis of 14 rand-omized controlled trials by Maki, et al [77] concluded that the use of ACE-inhibitors (particulary captopril and enalapril) in diabetics, resulted to a greater decrease in proteinuria and improvement in glomerular filtration rate as compared to other classes of antihypertensive agents. However, unlike the Lewis study, none of the included studies monitored clinical endpoints such as mortality and transplantation rates. Other studies [29,78] also reported the same favorable results in terms of reduction in proteinuria using calcium antagonists, particulary diltiazem and verapamil, although to a lesser extent. Thus, these two drugs are offered as alternatives.

5. Hypertension complicated by Stroke

In hypertensive patients with stroke, the choice of antihypertensive agents is the same as those

without stroke, i.e. ß-blockers or diuretics (Grade B Recommendation).

Summary of Evidence: There are few trials done on hypertensive patients with stroke. Most of them used ß-blockers or diuretics. The results of these studies [24,79] show that a) antihypertensive treatment reduces the incidence of congestive heart failure among stroke survivors and b) antihypertensive therapy is more effec-tive in preventing the first stroke than a recurrent stroke.

6. Hypertension complicated by Dyslipidemia

In hypertensive patients with dyslipidemia, the recommended drugs are also the same as those without dyslipidemia, i.e., ß-blockers or diuretics (Grade A Recommendation).

Summary of Evidence: The occurence of dyslipidemia was not a reason for exclusion in ß-blocker and diuretic trials. Adverse effects on lipid profile are theoretically hazardous, but these should be weighed against proven benefit in terms of mortality reduction or prevention of cardiovascular events [80]. Surprisingly, the expected magnitude of deterioration in the lipid profile was not demonstrated in large randomized controlled trials such as the VAII, USPHS, Oslo, MRC, ANBPS, IPPSH, HAPPHY, MAPHY, SHEP, EWPHE, & HEP [49]. The mean increase in total cholesterol ranged from 0.2 to 0.4 mmol/L while the influence on LDL-cholesterol & triglycerides were unclear.

7. Hypertension complicated by Peripheral Vascu-lar Disease

In hypertensive patients with peripheral vascular disease, ß-blockers should be used with caution (Grade B Recommendation).

Summary of Evidence: The use of fi-blockers in these patients may exacerbate symptoms of the disease. However, Radack and Beck reported in their meta-analysis that these drugs could be used safely in most patients with mild peripheral vas-cular disease, even if accompanied by intermittent claudication. However, the study was limited by a small sample size (n=127) [80-81]. Thus, up to the present time, there is no evidence for or against the use of vasodilators in this subset of patients.

8. Hypertension complicated by Chronic Obstruc-tive Pulmonary Disease and Asthma

a. In hypertensive patients with chronic obstruc-tive pulmonary disease (COPD), ß-blockers should be avoided (Grade A Recommenda-tion). ACE-inhibitors may be used but they

HYPERTENSION

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CPM 1ST EDITION

may aggravate cough already existing in these patients (Grade B Recommendation).

Summary of Evidence: ß-blockers are generally con-traindicatedin patients with chronic obstructive pul-monary disease [83]. This is particularly applicable to COPD patients with functional airflow obstruction [83]. The MAPHY study, in particular, excluded patients with obstructive lung disease whose symptoms were not controlled by stimulants [27]. On the other hand, ACE-inhibitors may cause cough in 10-15% of patients, thus its use may produce effects that could interfere with control of the respiratory disorder.

b. In patients with bronchial asthma, ß-blockers are contraindicated (Grade A Recommendation).

Summary of Evidence: fi-blockers, especially non-selective ß-blockers will precipitate or exacerbate the symptoms of bronchial asthma [83], thus asthmatics were excluded from ß-blocker trials.

SPECIAL CONDITIONS:

9. Hypertension in the Elderly

In hypertensive elderly patients, low dose thi-azide diuretics are the preferred agents (Grade A Recommendation). ß-blockers may be used as alternative agents (Grade B Recommendation).

Summary of Evidence: The use of low dose thiazide diuretics in the elderly (age range=60-84) has been shown to decrease cardiovascular morbidity and mor-tality as well as all-cause mortality in several meta-analyses [84-86]. Although hydrochlorothiazide 25 mg or Chlorthalidone was used, most of the effects can be achieved with lower doses, e.g. hydrochlorothiazide 12.5 mg/day [84].

ß-blockers in the above age group has also been shown in meta-analyses to decrease the same clinical endpoints. However, they are less effective than diuretics [85-86].

10. Hypertension in Pregnancy

a. In pregnant patients with Stage I (mild) or Stage II (moderate) hypertension, treatment can be started using oral medications. Alpha methyldopa is the preferred agent (Grade A). When methyldopa alone is ineffective, ß-blockers provide a 2nd option (Grade B Recommendation).

Summary of Evidence: The diagnosis of hypertension in pregnancy may be made using standard criteria used to diagnose hypertension in general. Classification of sever-

ity can likewise be made based on Table 4. In addition to classification according to etiology as having 1) chronic hypertension or 2) pregnancy-induced hypertension (also known as pre-eclampsia). A combination of the 2 conditions may occur, & is referred to as "superimposed pre-eclampsia" [87]. The 2 conditions may not always be easy to diffrentiate but clinical clues are summarized in Table 10. As the table indicates, distinguishing between the 2 causes of hypertension is important mainly for purposes of prognostication. Although both can lead to eclampsia (development of seizures) Pregnancy-induced hypertension often disappears after delivery.

A meta-analysis of trials using alpha methyldopa [88] in pregnant hypertensives (mostly pregnancy-induced hy-pertension) shows that the drug can effect 1) a reduction of the incidence of severe hypertension (OR=0.33; 95% Cl: 0.17, 0.63) and 2) a possible reduction in perinatal deaths (OR=0,58; 95% CL0.18,0.83. However, the possibility of harm has not been excluded with regards other end-points such as maternal death and ceasarian section rate.

A meta-analysis of trials using fi-blockers [89] in preg-nant hypertensives (mostly pregnancy-induced hyper-tension) shows that the drug can effect 1) a reduction in the incidence of severe hypertension (OR = 0.37; 95% Cl: 0.25, 0.53), 2) a possible reduction in hospitalization (OR = 0.51, 95% Cl: 0.32, 0.82), and 3) a possible reduc-tion in the incidence of respiratory distress syndrome (OR = 0.29,95% Cl: 0.14,0.63). However, the incidence of low birth weight infants was increased (OR = 1.55; 95% Cl: 1.1,2.2). In addition, the possibility of harm has not been excluded with regards to other endpoints such as maternal death and caesarian section rate/s.

Table 10. Differences between Pregnancy Induced Hypertension and Chronic Hypertension.

PREGNANCY- CHRONIC INDUCED Age Usually young (<30) Usually older (>30) Parity Usually primigravid Usually multigravid Onset After 2 wks AOG Before 20 wks AOG Weight Sudden Gradual gain and edema SystolicBP <160 >160 Funduscopic Spasm, edema AV nicking, exudates findings Proteinuria Present Absent Plasma Elevated Normal Uric acid Eclampsia Possible Possible (seizures) BP after Normal Elevated delivery


46

b. Pregnant patients with Stage III (severe) or Stage IV (severe or very severe), or with symptoms of impending target-organ damage (see Table 10) should be admitted and started first on IV therapy, while oral medications are titrated. The drugs may be used are hydrala-zine, clonidine, methyldopa, and labetalol (Grade B Recommendation).

Summary of Evidence: Drugs that have been used for the treatment of severe pregnancy-induced hypertension and pre-eclampsia include hydralazine, clonidine, meth-yldopa, ß-blockers, nifedipine and rarely, diazoxide. Although comparisons between these drugs have been made, there is no strong evidence to justify preference for any. It is generally recommended that an individual physician's familiarity should play a crucial role in the choice of a drug [90].

With regards to adverse effects, hydralazine has been reported to be relatively safe. The use of labetalol may lead to severe fetal and neonatal bradycardia. Diazox-ide, on the other hand, may lead to serious reduction in uteroplacental or even cerebral perfusion and hypergly-cemia in the newborn. Thus, the use of this drug is not advised. Fetal or neonatal effects of the maternal use of Ca antagonists is not yet known.

c. Data is insufficient to support calcium sup-plementation among non-pregnant women to prevent hypertension.

Summary of Evidence: Ca supplementation may reduce the risk of women developing HPN. However, the evidence is insufficient regarding important outcomes, such as caesarian section rates, intrauterine growth retardation or perinatal death. Further trials are needed to define its role in antenatal care.

11. Hypertension in Emergency and Urgent Situations

a. Hypertension may be complicated by acute life-threatening conditions such as those listed in Table 10. In such setting/s, there is a need for immediate blood pressure reduction. The agents that can be used for rapid control of hypertension are listed in Table 12 (Grade D Recommendation).

Summary of Evidence: Immediate reduction of BP in emergency situations may beneficially alter the course of the confounding disease. This is based on experts' opinions and pathophysiologic reasoning, rather than on actual randomized control trials. However, these asser-tions are so strong that a trial may never get underway because of the ethical constraints.

Oral preparations are now available for the emergency control of hypertension. These include captopril, cloni-dine & nifedipine (punctured, squeezed & swallowed). However, these drugs do not provide good control of the rate of BP reduction, a disadvantage blamed for numerous reports of unexpected myocardial or cerebral hypoperfusion [4,92,93]. Thus, the parenteral agents listed in Table 10 are preferred, specifically because of a more controlled rate of reduction of BP [94].

b. In Stage IV or very severe hypertension uncomplicated by situations listed in Table 11, oral antihypertensive agents should be given and control of blood pressure should be achieved within 3 days (Grade A Recom-mendation).

Summary of Evidence: One of the first RCT's conducted among American Veterans randomized patients with very severe hypertension [95]. The study was prema-turely terminated because patients in the placebo group suffered strokes in significant numbers. The earliest occured 3 days after randomization.

Table 11. Hypertension and Target Organ Disease.

ORGAN NOT ACUTELY ACUTELY LIFE SYSTEM LIFE THREATENING THREATENING

Cardiac LVH Acute coronary events: Coronary AMI atherosclerosis Unstable angina Acute LV failure Pulmonary congestion or Edema

Cerebro- TIA Intracranial vascular hemorrhage Thrombotic stroke Hypertensive encephalopathy

Peripheral Peripheral DissectingVascular occlusive disease aneurysms

Renal Nephrosclerosis Malignant nephrosclerosis

Ophthalmic Retinopathy Papilledema/ Optic nerve head edema

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CPM 1ST EDITION

Table 12. Drugs for Treatment of Hypertensive Crisis

Drugs* Dose** Onset of Adverse Special Action, Reactions Indications min.

PARENTERAL DRUGS

VASODILATORS

Sodium 0.3-10 ug/kg/min Instan- Nausea, vomiting, Hypertensive nitroprusside as IV infusion, taneous muscle twitching, encephalopathy, acute maximal dose for methemoglobinemia, intracranial hemor- no more than 10 cyanide toxicity, rhage, acute cerebral minutes hypotension infarction, acute left ventricular failure, acute coronary insufficiency, dissecting aneurysm, catechol- amine crisis, head injury, extensive body burns, malignant hypertension, post- operative hypertension

Nitroglycerine 5-100 ug/min 2-5 Headache, Acute left ventricular as IV infusion tachycardia, vomiting, failure, acute coronary methemoglobinemia insufficiency, post- operative hypertension (especially coronary bypass)

Hydralazine 10-20 mg IV 10 Tachycardia, Eclampsia, HC1 10-50 mg IM 20-30 headache, vomiting, extensivebody burns, aggravation of angina malignant pectoris, fluid hypertension, post- retention operative hypertension

ADRENERGIC INHIBITORS

Methyldopa 250-500 mg IV 30-60 Drowsiness Eclampsia, peri-op infusion hypertension

ORAL DRUGS

Nifedipine 5-10 mg PO, repeat 15-30 Rapid uncontrolled (not extended after 30 min reduction in blood release) pressure may precipitate circulatory collapse in patients with aortic stenosis

Captopril 25 mg PO, repeat 15-30 Hypotension, renal as required failure in bilateral renal artery stenosis

Clonidine 0.1-0.2 mg PO, 30-60 Hypotension, repeated every drowsiness, dry hour as required mouth to a total dose of 0.6 * Drugs such as Diazoxide, Phentolamine mesylate, Trimethaphan canisylate, and Labetalol hydrochloride are also used for

hypertensive emergencies but are not available locally. ** IV indicates intravenous; IM intramuscular, PO per orem

Modified from: 1. afford RW, Management of hypertensive crises, JAMA 1991; 266(6):83 2. The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High

Blood Pressure (JNC V), Ardi


48

12. Current Status of Herbal Preparations

No indigenous herbal preparations have been adequately tested.

Summary of Evidence: Among the many herbal prepa-rations being speculated as having anti-hypertensive properties, only "sambong" is undergoing a rigorous evaluation. At present, a randomized, double-blind crossover study is ongoing to test the efficacy of this herbal medicine among mild hypertensives [reference unpublished].

Previous studies on garlic failed to demonstrate a sig-nificant effect on blood pressure [96].

F. HOW CAN HYPERTENSION BE PREVENT-ED AMONG NORMOTENSIVES ?

Weight reduction among overweight individuals through moderate physical activity and reduced total caloric intake can decrease the incidence of hypertension (Grade B Recommendation).

Summary of Evidence. A significant risk reduction in the incidence of hypertension was demonstrated among normotensives subjected to weight reduction [97-99]. Specifically, the trials of Hypertension Prevention, Phase I reported an odds ratio of 0.66 (96% Cl:0.46-0.94) [99]. The weight reduction program involved a moderate increase in physical activity by brisk walking for 45 minutes 4-5 times a week as well as reduction in total caloric intake [99].

Table 13. Summary of Pharmacologic Recommendations

CONDITION DRUG OF CHOICE ALTERNATIVE DRUGS

1) Uncomplicated Beta-blocker or Diuretic ACE-inhibitor or Calcium Hypertension channel blocker

2) Hypertension + See Table 9 See Table 9 Ischemic Syndrome 3) Hypertension + CHF ACE-inhibitor ISDN + Hydralazine combination

4) Hypertension + a) IDDM Beta-blocker or Diuretic; Addition of ACE-inhibitor b) NIDDM Beta-blocker or Diuretic; Verapamil or Diltiazem Addition of ACE-inhibitor 5) Hypertension + Stroke Beta-blocker or Diuretic 6) Hypertension + Dyslipidemia Beta-blocker or Diuretic 7) Peripheral Vascular Disease Any* 8) Hypertension + COPD Any* or Asthma 9) Hypertension in the Elderly Diuretic Beta-blocker 10) Hypertension + Pregnancy a) Stage I and II Methyldopa Beta-blocker, Calcium antagonist (Nifedipine) b) Stage III IV Hydralazine or IV Clonidine or Methyldopa or Labetalol or Nifedipine 11) Hypertension in Emergency/ See Table 12 See Table 12 Urgency Situations * Caution on the use of Beta-blocker

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CPM 1ST EDITION

Table 1. Levels of Evidence for Rating Studies on the Accuracy of Diagnostic Tests

Level 1 ALL 5 OF THE FOLLOWING CRITERIA ARE SATISFIED

(a) There was an independent interpretation of the result of the diagnostic test (without knowledge of the result of the gold stand-ard).

(b) There was an independent interpretation of the result of the gold standard (without knowledge of the result of the diagnostic test).

(c) The study patients consisted of patients sus-pected (but not known) to have the disorder of interest.

(d) The diagnostic test & gold standard are both described in sufficient detail to allow reproducibility.

(e) The study population consists of at least 50 patients with, & 50 patients without the disorder of interest

Level 2 4 OF THE 5 CRITERIA ARE MET.Level 3 3 OF THE 5 CRITERIA ARE MET.Level 4 2 OF THE 5 CRITERIA ARE MET.Level 5 1 OF THE 5 CRITERIA ARE MET.Level 6 NONE OF THE 5 CRITERIA ARE MET.

Table 2. Levels of Evidence for RatingStudies on the Effectiveness of Treatment

Level 1 A randomized controlled trial (RCT) that demonstrates a statistically significant dif-ference in at least one major outcome - e.g., survival or major illness,

OR if the difference is not statistically significant,

an RCT of adequate sample size to exclude 25% difference in relative risk with 80% power, given the observed results.

Level 2 An RCT that does not meet the level 1 criteria.Level 3 A non-randomized trial with concurrent

controls selected by some systematic method (i.e., not selected on the basis of perceived suitability for one of the treatment options).

Level 4 Before-after study or case series (at least 10 patients) with historical controls or controls drawn from other studies.

Level 5 Case series (at least 10 patients) without controls.

Level 6 Case series (fewer than 10 patients) or case reports.

Table 3. Levels of Evidence for RatingStudies on Prognosis or Causation

Level 1 ALL 5 OF THE FOLLOWING CRITERIA ARE SATISFIED

(a) An inception cohort was formed. (b) Reproducible inclusion & exclusion criteria

were used. (c) Follow-up was complete for at least 80% of

subjects. (d) Statistical adjustment was carried out for

extraneous factors (confounders). (e) Reproducible descriptions of outcome

measures were used.Level 2 An inception cohort was formed but only 3

of the 4 remaining criteria were satisfied.Level 3 An inception cohort was formed but only 2

of the 4 remaining criteria were satisfied.Level 4 An inception cohort was formed but only 1

of the 4 remaining criteria were satisfied.Level 5 An inception cohort was formed but none

of the 4 remaining criteria were satisfied.Level 6 NONE OF THE 5 CRITERIA WERE

MET.

Table 4. Levels of Evidence for Rating Review Articles

Level 1 ALL 4 OF THE FOLLOWING CRITERIA ARE MET

(a) Comprehensive search for evidence. (b) Avoidance of bias in the selection of arti-

cles. (c) Assessment of the validity of each cited

article. (d) Conclusions supported by the data & analysis

presented.Level 2 3 of the 4 criteria are met.Level 3 2 of the 4 criteria are met.Level 4 1 of the 4 criteria are met.Level 5 NONE OF THE 4 CRITERIA ARE MET.

Appendix

SUMMARY OF CRITERIA FOR RATING EVIDENCE


50

Table 5. ALCOHOL EQUIVALENTS AND SUGGESTED DAILY ALLOWANCE

LIQUOR PROOF/VOLUME G/SHOT**, G/GLASS** DAILY ALLOWANCE WHISKEY J&B 43% volume 10 g/shot 3 shots Johnny Walker (Black) 86 proof 10 g/shot 3 shots Chivas Regal 40% volume 9.6 g/shot 3 shots Johnny Walker (Red) 43% volume 10 g/shot 3 shots Jim Beam 80 proof 9.6 g/shot 3 shots Cutty Sark 80 proof 9.6 g/shot 3 shots BRANDY Carlos I 40% volume 9.6 g/shot 3 shots Emperador 80 proof 9.6 g/shot 3 shots Fundador 40% volume 9.6 g/shot 3 shots Napoleon 36% volume 8.6 g/shot 3 shots VOS 80 proof 9.6 g/shot 3 shots RHUM Tanduay (Dark) 80 proof 9.6 g/shot 3 shots Tanduay ESQ 65 proof 7.8 g/shot 3.5 shots Tanduay 65 65 proof 7.8 g/shot 3.5 shots Añejo Rhum 80 proof 9.6 g/shot 3 shots Tanduay (White) 80 proof 9.6 g/shot 3 shots GIN Gilbey's 90 proof 10.8 g/shot 3 shots SM 80 proof 9.6 g/shot 3 shots Gin Kelly 80 proof 9.6 g/shot 3 shots McKevin's 90 proof 10.8 g/shot 2.5 shots Duncan 90 proof 10.8 g/shot 2.5 shots BEER Premium SMB 5% volume 14g/355 ml bottle 2 bottles Bartles & Jaymes 5% volume 13 g/320 mL bottle 2 bottles Heineken 5% volume 13.2 g/330 mL bottle 2 bottles Stag 3.9% volume 10 g/320 mL bottle 3 bottles COGNAC Camus 40% volume 9.6 g/shot 3 shots Hennesey 40% volume 9.6 g/shot 3 shots TEQUIIA Cuervo 40% volume 9.6 g/shot 3 shots VODKA Smirnoff 80 proof 9.6 g/shot 3 shots Absolute 80 proof 9.6 g/shot 3 shots SIOKTONG Kungfu 50 proof 6 g/shot 4.5 shots Vino Kulafu 50 proof 6 g/shot 4.5 shots Vino de Chino 50 proof 6 g/shot 4.5 shots Anis 70 proof 8 g/shot 3 shots WINE Carlo Rassi 10% volume 16 g/glass 2 glasses Mompo mass wine 13.8% volume 22 g/glass l¼ glasses Maria Clara Sangria 10% volume 16 g/glass 2 glasses Martini Bianci 16% volume 26 g/glass 1 glass Andre 11% volume 18 g/glass l½ glasses Blue Nun 11% volume 18 g/glass l½ glasses Le Piat dor 9.5% volume 15 g/glass 2 glasses Red Rose California 9.5% volume 15 g/glass 2 glasses Burgundy 12.5% volume 20 g/glass l½ glasses Asti Martini 7% volume ll g/glass 2½ glasses Mateus 10% volume 16 g/glass 2 glasses

*Shot = 30 cc **Glass = 200 cc PROOF : is defined as mixture of Ethanol & water containing 50% by volume of Ethanol FORMULA : Grams of ethanol/serving = (% volume) or (proof/2) X cc/serving X 0.8 (density of ethanol)

HYPERTENSION

51

CPM 1ST EDITION

Table 6. Antihypertensive Agents as Listed in the Philippine Pharmaceutical Directory (PPD), 1996.

ACE-INHIBITORS BETA-BLOCKERS Benazepril Atenolol Captopril Betaxolol Cilazapril Bisoprolol Delapril Carteolol Enalapril Esmolol Lisinopril Metoprolol Perindopril Nadolol Quinapril Oxprenolol Ramipril Pindolol Propranolol

CALCIUM CENTRALLY ACTING ANTAGONISTS DRUGS Amiodipine Diltiazem Clonidine Felodipine Guanfacine Isradipine Methyldopa Lacidipine Reserpine Manidipine Nicardipine Nifedipine Nimodipine A2 ANTAGONIST Nitrendipine Verapamil Losartan

DIURETICS VASODILATORS Acetazolamide Doxazocin Bumetamide Hydralazine Furosemide Prazosin Hydrochlorothiazide Sodium Nitroprusside Indapamide Spironolactone References 1. Carruthers SG, Larochelle P, Haynes RB, et al. Report

of the Canadian Hypertension Society Consensus Conference: 1. Introduction. Can Med Assoc J 1993; 149: 289,1993.

2. American Society of Hypertension. Recommendations for Routine BP Measurement by Indirect Cuff Sphygmomanometry. Am J Hypertens 1992; 5:207.

3. Frohlich ED, Grim C, Labarhte DR, et al. Recommen-dations for Human Blood Pressure Determinations bySphygmomanometers: Report of a Special Task Force Appointed by the Steering Committee, American Heart Association. Hypertension; 11:209A, 1988.

4. The Fifth Report of the Joint National Committee on Detection, Evaluation, & Treatment of High BP (JNC V). Arch Intern Med; 153:154,1993.

5. Whetworth JA, et al. Australian Consensus Conference on Hypertension. Med J Aust; 160:s2sl6,1994.

6. Haynes RB, Laucourciere Y, Rabkin SW, et al. Report of the Canadian Hypertension Society Consensus Conference: 2. Diagnosis of Hypertension in Adults. Can Med Assoc J; 149:409,1993.

7. Appel LJ, Stason WB. Ambulatory Blood Pressure Monitoring & Blood Pressure Self-measurement in the Diagnosis & Management of Hypertension. Ann Intern

Med; 118:867, 1993. 8. Collins R, Peto R, MacMahon S, et al. Blood Pressure,

Stroke, & Coronary Heart Disease. Part 2, Short Term Reductions in BP: Overview of Randomized Drug Trials in the Epidemiological Context. Lancet; 335:827, 1990.

9. Littenberg B, Garber AM, Sox HC. Screening for Hypertension. Ann Intern Med; 122:192, 1990.

10. Littenberg B. A Practice Guideline Revisited: Screening for Hypertension. Ann Intern Med; 122:937, 1995.

11. Rosner B, BF. Screening for hypertension - Some Statistical Observations. J Chron Dis; 30:7,1977.

12. Rosner B, Polk BF. The Implications of Blood Pressure Variablity for Clinical & Screening Purposes. J Chron Dis; 32:451, 1979.

13. Idem. The Instability of BP Variability Over Time. J Chron Dis; 34:135,1981.

14. Idem. Predictive Values of Routine Blood Pressure Measurements in Screening for Hypertension. Am J Epidemiol 1983; 117:429-442.

15. Shepard DS. Reliability of BP Measurements: Implications for Designing & Evaluating Programs to Control Hypertension. J Chron Dis;34:191,1981.

16. Donner AD, Young C, Bass M. Sequential screening for hypertension in primary care. J Chron Dis; 32:577, 1979.

17. Donner A, Bull S. The Mean Versus the Minimum as a Criterion for Hypertension Screening. J Chron Dis; 34:527, 1981.

18. Fletcher R.H. Clinical Epidemiology: A Basic Science for Clinical Medicine, 2nd ed. Boston: Little Brown & Co., 1991.

19. Veterans Administration Cooperative Study Group on Anti-hypertensive Agents. Effects of Treatment on Mortality in Hypertension: II Results in Patients with Diastolic BP Averaging 90 through 114 mmHg. JAMA; 213:1143, 1970.

20. Medical Research Council Working Party. MRC Trial of Treatment of Mild Hypertension: Principal Results. Br Med J; 291:97, 1985.

21. Coope J, Warrender TS. Randomized Trial of Treatment of Hypertension in the Elderly in Primary Care. Br Med J; 293:1145, 1986.

22. Dahlof B, Lindholm L, Hansson L, et al. Morbidity & Mortality in the Swedish Trial in Old Patients with Mild Hypertension (STOP-HPN). Lancet; 338:1281, 1991.

23. Neaton JD, Grimm RH, Prineas RJ, et al. Treatment of Mild Hypertension Study (TOMHS) Final Results. JAMA; 270:713,1993.

24. Hypertensive-Stroke Cooperative Study Group. Effect of Anti-hypertensive Treatment on Stroke Recurrences. JAMA; 229:409,1974.

25. D'Agostino RB: Risk Factors for Coronary Heart Disease. BMJ; 303:385, 1991.

26. Wassertheil-Smoller S, Blaufox MD, Oberman AS, et al. The Trial of Antihypertensive Interventions & Management (TAIM) Study: Adequate Weight Loss Alone & Combined with Drug Therapy in the Treatment of Mild Hypertension. Arch Intern Med; 152:131, 1992.

27. Wikstrand J, Warnold I, Disson G, et al. Primary Prevention with Metoprolol in Patients with Hypertension. Mortality Results from the MAPHY Study. JAMA; 259:1976, 1988.

28. ß-blocker Heart Attack Trial Research Group. A Randomized Trial of Propranolol in Patients with AMI. I. Mortality Results. JAMA;247:1707,1982.

29. Bakris GL. Hypertension in Diabetic Patients: An Overview of Interventional Studies to Preserve Renal Function. Am J Hypertens; 6:140s, 1993.


52

30. McCormick KA, Moore SR, Seigel RA (eds). Clinical Practice Guideline Development Methodology Perspectives. US Department of Health & Human Services. Nov 1994; AHCPr Pub No. 95-009.

31. Sox HC, Garber AM, Littenberg B. The Resting ECG as a Screening Test. A Clinical Analysis. Ann Intern Med; iii:489,1989.

32. Pornhlit DW, Bove KE, Norris RJ. A Critical Appraisal of the Electrocardiographic Criteria for the Diagnosis of LVH. Circulation; 40:185,1969.

33. Reichek N, Devereux RB. LVH: Relationship of Anatomic, Echocardiographic & Electrocardiographic Findings. Circ ;63:1391,1981.

34. The Multi-Sectoral Task Force on the Detection and Management of Hypercholesterolemia. Clinical Practice Guidelines on the Detection and Management of Hypercholesterolemia. PJC; 24(4):127, 1996.

35. Woythaler JN, Singer SL, Kwan OL, et al. Accuracy of Echocardiography versus Electrocardiography in Detecting LV Hypertrophy: Comparison with Postmortem Measurements. J Am Coll Cardiol;2:305,1983.

36. Devereux RB, Koren M), De Simone G, Okin PM, Kligfield P. Methods for Detection of Left ventricular Hypertrophy: Application of Hypertensive Heart Disease. Eur H J; 14 Suppi D:8, 1993.

37. Dahlof B. Pennert K, Hansson L. Reversal of left Ventricular Hypertrophy in Hypertensive Patients: A Meta-analysis of 109 Treatment Studies. Am J Hypertens; 5:95,1992.

38. Sheps GS, Pickering TG, White WB, et al. Ambulatory Blood Pressure Monitoring (ACC Position Statement). JACC; 23:1511,1994.

39. Sackett D.L. Clinical Epidemiology: The Essentials, 2nd ed. Baltimore: Williams & Wilkins, 1988.

40. Pooling Project Research Group. Relationship of Blood Pressure, Serum Cholesterol, Smoking Habit, Relative Weight & ECG Abnormalities to Incidence of Major Coronary Events: Final Report of the Pooling Project. J Chron Dis; 31:201, 1978.

41. Langford HG, Davis BR, Blaufox MD, et al. Effect of Drug & Diet Treatment of Mild Hypertension on Diastolic BP. Hypertension; 17:210-217, 1991.

42. Schotte DE, Stunkard AJ. The Effects of Weight Reduction on Blood Pressure in 301 Obese Patients. Arch Inern Med; 150:1701, 1990.

43. Kelly G & McClellan P. Antihypertensive Efects of Aerobic Exercise. A Brief Meta-analytic Review of Randomized Trials. Am J Hypertens; 7:115,1994.

44. World Hypertension League. Alcohol & hypertension - Implications for Management: A Consensus Statement by the World Hypertension League. J Hum Hypertens; 5:1854,1991.

45. Kaplan MM. Moderate Sodium Restriction. Am J Hypertens; 3:518,1990.

46. Cutler JA, Follman D, Elliot P, Suh I. An Overview of Randomized Trials of Sodium Reduction and BP. Hypertension; 17 (Suppi I): 1-27-1-33,1991.

47. Law MR, Frost CD, Wald NJ. By How Much Does Dietary Dalt Reduction Lower Blood Pressure? Ill: Analysis of Data from Trials of Salt Reduction. BMJ; 302:819,1991.

48. Behavior Changes & the Prevention of High Blood Pressure: Workshop II. Circulation; 88(3): 1387, 1993.

49. Elliot P. Nutritional Factors in BP. J Hum Hypertens; 8(8):595,1994.

50. Swedish Consensus Statement (Journal of Internal Medicine/Acta Scandinavia).

51. Ogilvie RI, et al. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic

Treatment of Essential Hypertension. Can MedAssoc J; 149:575, 1993.

52. Wikstrand J, Berglund G, Tuomilehto J. ß-blockade in the Primary Prevention of Coronary Heart Disease in Hypertensive Patients. Review or Present Evidence. Circ; 84 (Suppi VI): VI-93 - VI-100,1991.

53. Edelson JT, Weinstein MC, Tosteson AN, et al. Long-term Cost- Effectiveness of Various Initial Monotherapies for Mild to Moderate Hypertension. JAMA; 263:408, 1990.

54. Pepine CJ, Cohn PP, Deedwania PC, et al. Effects of Treatment on Out-come in Mildly Symptomatic Patients with Ischemia During Daily Life. The Atenolol Silent Ischemia Study (ASIST). Circulation; 90(2):762, 1994.

55. Yusuf S, Wittes J, Friedman L. Overview of Results of Randomized Clinical Trials in Heart Disease II: Unstable Angina, Heart Failure, Primary Prevention with Aspirin & Risk FactorModification. JAMA; 260:2259.

56. ISIS I (1st International Study of Infarct Survival) Collaborative Group. Randomized Trial of IV Atenolol Among 16,027 Cases of Suspected Acute Myocardial Infarction: ISIS-I. Lancet; 2:57, 1986.

57. Pedersen TR. The Norwegian Multicenter Study of Timolol after MI. Circ; (Suppi I) 67:49.1983.

58. Lau J, Amman EM, Jimenez-Silva J, et al. Cumulative Meta-analysis of Therapeutic Trials for Myocardial Infarction. NEJM; 248,1992

59. Yusuf S, Wittes J, Probstfield. Evaluating Effects of Treatment in Subgroups of Patients Within Clinical Trial: The Case of Non-Q wave MI & fi-blockers, AJC; 66:220,1990.

60. ISIS-4: A Randomised Factorial Trial Assessing Early Oral Captopril; Oral Mononitrate, & Intravenous Magnesium Sulphate in 58,050 Patients with Suspected Acute Myocardial Infarction. ISIS-4 (Fourth International Study of Intact Survival) Collaborative Group. Lancet; 345:669, 1995.

61. The Danish Study Group on Verapamil in Myocardial Infarction. Effect of Verapamil on mortality & major events after AMI (The Danish Verapamil Infarction Trial II - DAVIT II). Am J Cardio; 66:779,11990.

62. The Multicenter Diltiazem Post-Infarction Trial Research Group. The Effect of Diltiazem on Mortality & Re-infarction After Acute Myocardial Infarction. N Engi J Med; 319:385, 1988.

63. Furberg CD, Psaty BM, Meyer JV. Nifedipine Dose-Related Increase in Mortality in Patients with CHD. Circulation; 92:1326, 1995.

64. Yusuf S. Calcium Antagonists in Coronary Artery Disease & Hypertension - Time for Reevaluation? Circulation; 92:1079,1995.

65. Fagan TC. Calcium Antagonist and Mortality. Another Case of the Need for Cinical Judgement. Arch Intern Med; 155:2145, 1995.

66. Furberg CD, Psaty BM. Should Dihydropyridines be Used as First-line Drug in Hypertension? The Con side. Arch Intern Med; 155:2157,1995.

67. Opie LH, Messerii FH. Nifedipine and Mortality: Grave Defects in the Dossier. Circulation; 92:1068-1073, 1995.

68. Kloner RA. Nifedipine in Ischemic Heart Disease. Circ; 92:1074,1995.

69. Epstein M. Calcium Antagonists Should Continue to be Used for First-line Treatment of Hypertension. Arch Intern Med; 155:2150,1995.

70. Messerii, FH. Case-control Study, Meta-Analysis, & Bouillabase: Putting the Calcium Antagonist Scare into Context. Ann Int Med; 123:888, 1995.

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71. The SOLVD Investigators. Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fraction & Congestive Heart Failure. N Engi J Med; 325:293, 1991.

72. The Consensus Trial Study Group. Effect of Enalapril on Mortality in Severe Congestive Heart Failure: Results of t he Cooperative North Scandanavian Enalapril Survival Study (Consensus). N Engi J Med; 316:1429,1987.

73. Cohn JN, Johnson G, Ziesche S. et al. A Comparison of Enalapril with Hydralazine-Isosorbide Dinitrate in the Treatment of Chronic Congestive heart failure. N Engi Med; 325:303, 1991.

74. Cohn JN, et al. Effect of Vasodilator Therapy on Mortality in Chonic Congestive Heart Failure. N Engi J Med; 314:1547, 1986.

75. SHEP Cooperative Research Group. Systolic Hypertension in the Elderly Program. JAMA; 265:3255, 1991.

76. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of ACE Inhibitor in Diabetic Nephropathy. N Eng J Med; 329: 1456, 1993.

77. Maki DD, Ma JZ, Louis TA, Kasiske BL, et al. Long-term Effects of Antihypertensive Agents on Proteinuria & Renal Function. Arch Intern Med;155:1073, 1995.

78. Slataper R, Vicknair N, Sadler LRD, Bakris GL, et al. Comparative Effects of Different Antihypertensive Treatments on Progression of Diabetic Renal Disease. Arch Intern Med; 153:973, 1993.

79. Carter AB. Hypotensive Therapy in Stroke Survivors. Lancet; 485, 1970.

80. McCormick KA, Moore SR, Siegel RA (eds). Clinical Practice Guideline Development Methodology Perspectives. US Dept. of Health & Human Services; AHCPR Publ No. 95-009, Nov 1994.

81. Radack K, Deck C. C-adrenergic Blocker Therapy does not Worsen Intermittent Claudication in Subjects with Peripheral Arterial Disease. A Meta-Analysis of Randomized Clinical Trials. Arch Intern Med; 151:1769, 1991.

82. Thadani U, Whitsett TL. fi-adrenergic Blocker & Intermittent Claudication: Time for Reappraisal. Arch Intern Med; 151:1705,1991.

83. ATS Statement: Standards for the Diagnosis & Care of Patients with Chronic Obstructive Pulmonary Disease. Official Statement of the American Thoracic Society. American Journal of Respiratory & Critical Care Medicine; 152(5)Suppl:578 & 587, 1995.

84. Beard K, Bulpitt C, Mascie-Taylor H, et al. Management of Elderly Patients with Sustained Hypertension. BMJ; 304:412, 1992.

85. Thijs L. Fagard R, Lijnen, et al. Why is Antihypertensive Drug Therapy Needed in Elderly Patients with Systodiastolic Hypertension? J Hypertens Suppi; 12(6):s25, 1994.

86. Insua JT, Sacks HS, Tai-Shing, et al. Drug Treatment of Hypertension in the Elderly: a Meta-analysis. Ann Intern Med; 121(5):355,1994.

87. Collins R, Wallenberg HCS. Hypertension in Pregnancy. Effective Care in Pregnancy & Childbirth. The Cochrane Pregnancy & Childbirth Database. Issue 2, 1995.

88. Collins R, Duley L. Methyldopa-based therapy in the treatment of pre-eclampsia. m: Pregnancy & Childbirth Module (eds, Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP), "Cochrane Database of Systematic Reviews": Review No. 03997, 29 July 1992. Published thru "Cochrane Updates on Disk", Oxford: Update Software, Spring, 1993.

89. Collins R, Duley L. fi-blockers in the treatment of pre-eclampsia. In Pregnancy & Childbirth Module (eds, Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP), "Cochrane

Database of Systematic Reviews": Review No. 03998, 20 April 1993. Published through "Cochrane •Updates on Disk", Oxford: Update Software, Spring, 1993.

90. Duley L. Calcium channel blockers in pregnancy hypertension. In: Pregnancy & Childbirth Module (eds, Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP), "Cochrane Database of Systemic Reviews": Review No. 07075, 30 July 1992. Published through "Cochrane Updates on Disk", Oxford: Update Software, Spring 1993.

91. Collins R, Duley L. IV Labetalol vs IV Diazoxide in severe pre-eclampsia. In: Pregnancy & Childbirth Module (eds, Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP), "Cochrane Database of Systemic Reviews": Review No. 04400,20 April 1993. Published through "Cochrane Updates on Disk", Oxford: Update Software, Spring 1993.

92. O'Mailia JJ, Sander GE, Giles TD. Nifedipine-associated Myocardial Ischemia or Infarction in the Treatment of Hypertensive Urgencies. Ann Intern Med; 107(2): 185, 1987.

93. Messerii FH, Kowey P, Grodzicki T. Sublingual nifedipine for hypertensive emergencies. Lancet; 338:881,1991.

94. Giffoid, RW. Management of Hypertensive Crises. JAMA; 266:829,1991.

95. Veterans Administration Cooperative Study Group on Anti-hypertensive Agents. Effects of Treatment on Morbidity in Hypertension: Results in Patients with Diastolic Blood Pressure Averaging 115 through 129 mmHg. JAMA; 202:1028, 1967.

96. Silagy CA, Neil HAW. A Meta-analysis of the Effects of Garlic on Blood Pressure. J Hypertens; 12:463, 1994.

97. National High Blood Pressure Education Program Working Group on Primary Prevention of Hypertension. Arch Intern Med; 153:186,1993.

98. Hypertension Prevention Trial Research Group. The Hypertension Prevention Trial: Three Year Effects of Dietary Changes in Blood Pressure. Arch Intern Med; 150:153,1990.

99. The Trials of Hypertension Prevention Collaborative Research Group. The Effects of Non-pharmacologic Interventions in Blood Pressure in Persons with High Normal Levels: Results of the Trials of Hypertension Prevention Phase I. JAMA: 267:1213, 1992.


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Acknowledgements

Critiques of DraftMilagros Arroyo, MD, Philippine Society of OphthalmologyRenato Dantes, MD, Medical Director, Boehringer IngelheimConrado Dayrit, MD, VP - Medical Affairs, United Laboratories Inc.Mario Festin, MD, U.P. Coll. of Medicine, Clinical Epidemiology UnitJesus Fojas, MD, Dean, MCU-FDTMF College of MedicineMr. Rene Martinez, VP-Marketmg Services, GX Intl.Caesar L. Mendoza, MD, Medical Center ManilaSandra Tankeh-Torres, MD, Medical Director, PfizerCecilia Tomas, MD, U.P. College of Medicine, Dept. of PhysiologyParticipants in the First Public Forum Mr. Jorge Maravilla, LR Imperial, Inc.Mr. Frederick Farol, Therapharma, Inc.Ms. Shirly Fuentes, Pfizer Inc.Ms. Dory Guerrero, Boehringer Ingelheim, Inc.Mr. Gerry Arnedo, Pfizer, Inc.Dr. Renato Dantes, Boerhinger Ingelheim, Inc.Mr. Gilbert Donato, Merck, Inc.Ms. Jeanette Rogacion, Warner-Lambert (Parke-Davis)Dr. Virgilio Castro, UST Hospital/Philippine Obstetrics and Gynecology SocietyMr. Carlo Estrada, Hoechst Marion RousselMr. Romeo Albornoz, Hoechst Marion RousselDr. Francis Domingo, Servier, Inc. (Med-Asia)Ms. Odette Magno, Bristol-Myers Squibb, Phils.Mr. Henry Lim, Roche, Phils.Dr. Felicidad Cua-Lim, Philippine College of PhysiciansDr. Ronald Yutangco, Philippine Association of OphthalmologyDr. Joel Elises, Philippine Pediatrics SocietySister Francesca San Diego, Philippine Nurses AssociationMs. Precy Cruz, Occupational Health Nurses Assoc. of the Phils.Dr. Florencio Pine, Philippine Society of NephrologyDr. Eugene Ramos, Phil. Col. of Physicians/Bristol-Myers Squibb, Phils.Dr. Albert Bautista, Synthelabo, Inc.Dr. Corazon Almirante, Fetus as a Patient Institute of the PhilippinesDr. Raffy Castillo, Phil. Society of Hypertension / Phil. Heart Assoc.Dr. Ma. Antonia Yamamoto, Phil. Association of Family PhysiciansDr. Tes Somera-Cucueco, DOLEDr. Allan Ruales, Philippine Medical Association / MCU-FDTMFDr. Liberty Fajutrao, U.P. Coll. of Medicine Clinical -Epidemiology UnitDr. Elias Imperial, Bicol Heart CenterDr. Luciene Villacin, Cardiovascular Research GroupMr. Gerry Macutay, Medical Clerk, U.P. College of MedicineMs. Josephine Manansala, Medical Clerk, U.P. College of MedicineMyrna Abello, WVSU College of MedicineDr. Felix Eduardo Punzalan, Cardiovascular Research GroupDr. Armando Bolivar, Philippine College of Occupational MedicineDr. Conrado Dayrit, National Academy of Science and TechnologyDr. Joselito Atabug, UST- Dept. of Medicine / PHAProf. Maria Lourdes Amarillo, UP -College of Medicine, Clinical Epidemiology UnitDr. Paul Salandanan, FEU HospitalDr. Adriano dela Paz, Philippine Heart CenterDr. Vie Fileto Chua, FEU HospitalDr. Romiro Babanan, FEU HospitalDr. Amaryllis 0. Yazon, Fetus as a Patient Institute of the Phils.Mr. Jayvee Cruz, UP College of Nursing / Phil. Nurses AssociationDr. Oscar Naidas, St. Luke's Medical Center/Philippine Society of NephrologyDr. Leni Iboleon, St. Luke's Medical Center/PMADr. Ofelia P. Borje, Philippine Society of Pediatric Cardiology / PHAMs. Ma. Patrocinia de Guzman, Food & Nutrition Research mst./DOSTDr. Ramon Abarquez, Jr., Philippine Society of HypertensionDr. Esperanza Cabral, Philippine Society of HypertensionDr. Gregorio Patacsil, Jr., Philippine Society of HypertensionDr. Antonio Dans, Cardiovascular Research GroupDr. Desiree Narvaez, Department of HealthDr. Bernadette Tumanan, Philippine Society of HypertensionMs. Felicidad Velandria, Food and Nutrition Research InstituteDr. Elizabeth Pacheco, Philippine General Hospital/ Philippine Society of Endocrinology and Metabolism

HYPERTENSION

55

CPM 1ST EDITION

ACE InhibitorsBenazepril Cibacen ...............................139Captopril Capoten ..............................140Cilazapril Vascace ...............................140Delapril Cupressin ............................140Enalapril Renitec. ...............................140Lisinopril Zestril. ................................140Perindopril Coversyl ............................ 140Quinalapril Accupril................ ............. 142Ramipril Ramace............... ............... 142 Tritace ................................142Spirapril Wandopres........... .............. 142CaptoprillHydrochlorothiazide Capozide.............. .............. 142Cilazapril/Hydrochlorothiazide Capozide........ .................... 142Hydrochlorothiazide Vascace Plus........ .............. 142

Angiotensin II AntagonistLosartan Cozaar ................................142Valsartan Diovan ... ......... ..................NP"

Beta-BlockersAtenolol Serten ..................................129 Tenormin ........................... 130 UL Atenolol ....................... 130Betaxolol Kerlone .............................. 130Bisoprolol Concore ............................. 130Carteolol Mikelan ............................. 130Metoprolol Betaloc .............................. 130 Betazok ................................l31

Drugs Mentioned in the Treatment GuidelineThe following index lists therapeutic classifications as recommended by the treatment guideline. For the prescriber's reference, available drugs are listed under each therapeutic class.

Cardiosel ........................... 131 USA Metoprolol ........... .....131Nadolol Corgard .............................. 131Pindolol Visken ................................ 131Propranolol Bedranol.. .......................... 131 Duranol. ............................. 131 Inderal... ............................ 132 Propranolol- Phoenix... ........................ 132 Propranolol- Scanpharm. ..................... 132 UL Propranolol ..................132Sotalol Sotalex ............................... 132AtenolollChlorthalidone Tenoretic ......... .................. 132MetoprolollHydrochlorothiazide Betazide ............................. 132Pindololl /Clop amide Viskaldix. .......................... 132

Calcium Channel BlockersAmiodipine Norvasc. ............................ 132Diltiazem Dilatam .............................. 134 Diltelan ............................. 134 Dilzem/DilzemSA/SR ........134 Servazen .............................134 Tildiem .............................. 134 Zilden. ............................... 134Felodipine Munobal ............................ 134 PlendilER. ......................... 134Isradipine Dynadrc . ........................... 134 IcazSRO. ........................... 136Lacidipine Lacipil. .............................. 136Manidipine Caldine. ............................. 136 Minadil .............................. 136Nicardipine Cardepine .......................... 136 Selevax. ............................. 136Nifedipine Adalat.. .............................. 136

Calcibloc. .......................... 136 Cardionorm .......... ............ 138 Darat.. ................................ 138 Fedcor. ............................... 138 Nifelan . ............................. 138Nitrendipine Baypress.. .......................... 138Verapamil Hinorm.... .......................... 138 Isoptin/Isoptin SR ..............138 Verelan ................................139AtenolollNifedipine Niften. ................................ 139

Centrally-Acting DrugsClonidine Catapres..... ........................ 126 Catapres TTS ... ................. 126 Melzin. .............................. 127Guanfacine Estulic ................................ 127 Methyldopa Aldomet. ............................ 127 Dopetens ........................... 127 Meldopa ............................ 127 Mendonil. .......................... 127 UL Methyldopa ............ .....127 Moxonidine Cynt. .................................. 127 Physiotens ......................... 129 Reserpine Rauverid.. .......................... 129ReserpinelClopamidel Dihydroergocristine mesylate Brinerdin/ Brinerdin Mite.. .............. 129ReserpinelHydralazinelHydrochlorothiazide Ser-Ap-Es. ......................... 129

DiureticsAcetazolamide Diamox. ............................. 124Bumetanide Burinex. ............................. 124Furosemide Aquadrine .......................... 124 Flexamide. ......................... 124 Fretic. ................................ 124 Frusema. ............................ 124 Furoscan. ........................... 124


56

Lasix. ................................. 124 Lasix High Dose ............... 125 Lasix Long 30 ...........,........125 USALab Furosemide. .................... 125 YSP Furosemide. .................l25Hydrochlorothiazide Dichlotride ......................... 125Indapamide Natrilix .............................. 125Spironolactone Aldactone .......................... 125AmiloridelFurosemide Frumil. ............................... 126AmiloridelHydrochlorothiazide Moduretic. ......................... 126SpironolactonelButizide Aldazide. ........................... 126SpironolactonelFurosemide Lasilactone. ....................... 126

VasodilatorsDoxazosin Carduran. ........................... 129

Hydralazine Apresoline.. ....................... 129Prazosin Minipress... ........................ 129

philippine society of hypertension - the filipino doctor 1st ed hypertension.pdfphilippine society...

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