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Hipertensión ArterialHipertensión Arterial

20082008

Enfermedad cardiovascularEnfermedad cardiovascular

HTA es el principal factor que contribuye HTA es el principal factor que contribuye al riesgo de enfermedad cardiovascular.al riesgo de enfermedad cardiovascular.

El segundo contribuyente al mayor riesgo El segundo contribuyente al mayor riesgo es que la población llega a mayor edad y es que la población llega a mayor edad y tiene mayor obesidadtiene mayor obesidad

Enfermedad CardiovascularEnfermedad CardiovascularEdad y HTAEdad y HTA

Percent Developing Percent Developing HypertensionHypertension

Interval (years)Interval (years) WomenWomen MenMen

AgeAge 5555 6565 5555 6565

1010 5252 6464 5656 7272

1515 7272 8181 7878 8585

2020 8383 8989 8888 9090

Vasan et al. JAMA 2002;287:1003

LIFETIME RISK OF DEVELOPING HYPERTENSION IN FRAMINGHAM

SUBJECTS NORMOTENSIVE AT AGE 55 OR 65

Enfermedad cardiovascularEnfermedad cardiovascularHTA y edadHTA y edad

White-Coat Effect with Age

Mansoor et al. J Hum Hypertens 1996;10:87

Enfermedad CardiovascularEnfermedad Cardiovascular

Tercer factor que contribuye es el Tercer factor que contribuye es el inadecuado control de la Hipertensión:inadecuado control de la Hipertensión:

EEUU : 29 %EEUU : 29 %

Canadá : 17 %Canadá : 17 %

Europa : < 10 % (Inglaterra, Alemania Europa : < 10 % (Inglaterra, Alemania Italia ,España y suecia ) Italia ,España y suecia )

Riesgos e HipertensiónRiesgos e Hipertensión

Racional para reducir la PARacional para reducir la PA

Definición operacional Definición operacional Hipertensión ArterialHipertensión Arterial

Hipertension es ... “el nivel de Presion Hipertension es ... “el nivel de Presion sanguinea en donde los beneficios de la sanguinea en donde los beneficios de la accion (i.e. intervencion terapeutica) accion (i.e. intervencion terapeutica) exceden a los de la inaction.”exceden a los de la inaction.” Evans and Rose Brit Med Bull 1971;27:37-42Evans and Rose Brit Med Bull 1971;27:37-42

Cambios en la clasificación de HTACambios en la clasificación de HTA

Guías de Nueva ZelandaGuías de Nueva Zelanda

Guías europeasGuías europeas

Las diferencias en las guías , proponen un Las diferencias en las guías , proponen un cambio al enfrentar el problema de HTA, cambio al enfrentar el problema de HTA, que es el de reemplazar el manejo de que es el de reemplazar el manejo de factores de riesgofactores de riesgo por por RiesgosRiesgos

White-Coat Effect with Age

Mansoor et al. J Hum Hypertens 1996;10:87

Monitoreo ambulatorio domiciliarioMonitoreo ambulatorio domiciliario

Treatment Strategies andTreatment Strategies andRisk StratificationRisk Stratification

Blood PressureStages (mm Hg) Risk Group A Risk Group B Risk Group C

High-normal(130-139/85-89)

Lifestyle modification Lifestyle modification Drug therapy*Lifestyle modification

Stage 1(140-159/90-99)

Lifestyle modification(up to 12 months)

Lifestyle modification(up to 6 months)**

Drug therapyLifestyle modification

Stages 2 and 3( 160/ 100)




*For those with heart failure, renal insufficiency, or diabetes.**For those with multiple risk factors, clinicians should consider drugs as initial therapy plus lifestyle modifications.

JNC 6

Classification and Management Classification and Management of BP for adultsof BP for adults

BP BP classificationclassification

SBP* SBP* mmHgmmHg

DBP* DBP* mmHgmmHg

Lifestyle Lifestyle modificationmodification

Initial drug therapyInitial drug therapy

Without compelling Without compelling indication indication

With compelling With compelling indicationsindications

NormalNormal <120<120 and <80and <80 EncourageEncourage

PrehypertensionPrehypertension 120–139120–139 or 80–89or 80–89 YesYes No antihypertensive drug No antihypertensive drug indicated.indicated.

Drug(s) for compelling Drug(s) for compelling indications. indications. ‡‡

Stage 1 Stage 1 HypertensionHypertension

140–159140–159 or 90–99or 90–99 YesYes Thiazide-type diuretics for Thiazide-type diuretics for most. May consider ACEI, most. May consider ACEI, ARB, BB, CCB, or ARB, BB, CCB, or combination.combination.

Drug(s) for the Drug(s) for the compelling compelling indications.indications.‡‡

Other Other antihypertensive antihypertensive drugs (diuretics, drugs (diuretics, ACEI, ARB, BB, CCB) ACEI, ARB, BB, CCB) as needed. as needed.

Stage 2 Stage 2 HypertensionHypertension

>>160160 or or >>100100 YesYes Two-drug combination for Two-drug combination for mostmost†† (usually thiazide-type (usually thiazide-type diuretic and ACEI or ARB or diuretic and ACEI or ARB or BB or CCB).BB or CCB).

*Treatment determined by highest BP category.†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. JNC 7 slideset

Sudden Deaths by Time of Day

Peckova et al. Circulation 1998;98:31

Low Dose Diuretics vs. Others

From Psaty BM et al. JAMA 2003;289:2534

The Reasons Why Low-Dose Diuretics Should be Initial Therapy

1. They reduce cardiovascular morbidity and mortality.

2. They lower blood pressure, particularly in patients consuming excessive sodium.

3. They enhance the antihypertensive efficacy of all other antihypertensive drugs.

4. They rarely cause side effects.

5. They reduce calcium loss and osteoporosis.

6. They are relatively inexpensive.

Results of Different Levels of Blood Pressure Control in Results of Different Levels of Blood Pressure Control in Hypertensive Patients Hypertensive Patients with Type 2 Diabeteswith Type 2 Diabetes: B-Blocker compared : B-Blocker compared with ACE Inhibitor-Based Treatment Programwith ACE Inhibitor-Based Treatment Program

8.4-year follow-up of 1148 subjects (achieved blood pressure of 8.4-year follow-up of 1148 subjects (achieved blood pressure of 144/82 mm Hg compared with 154/87 mm Hg)144/82 mm Hg compared with 154/87 mm Hg)

Reduced risk of:Reduced risk of: Stroke (44%)Stroke (44%) Fatal strokes (58%)Fatal strokes (58%) Death related to diabetes (32%)Death related to diabetes (32%) Heart failure (56%)Heart failure (56%) Fatal and nonfatal coronary heart disease events (21%) (trend Fatal and nonfatal coronary heart disease events (21%) (trend

but not significant)but not significant)

• No difference in outcome between a captopril-based and an atenolol based treatment program

UKPDS . BMJ 1998;317:703-713

Systolic and Diastolic Blood Pressure Systolic and Diastolic Blood Pressure after Randomizationafter Randomization

N Engl J Med. 2003;348(7):583-592.

Diastolic

6083

6035 5583 5487 4320 1183

Systolic

6083

6035 5585 5487 4323 1183

ACEI

Diuretic

0

75

80

85

90

95

130

140

150

160

170

0 1 2 3 4 5

CV Events in Swedish Trial in Old Persons (Stop-2)

Conventional Rx (diuretics and B-blockers)compared to ACE-Is and CCBsNo difference in BP outcomesNo overall difference in EVENTS

Lancet 1999;354:751

Results of An ARB-Based (Losartan Compared to a B-Blocker Results of An ARB-Based (Losartan Compared to a B-Blocker Based (Atenolol) Treatment Program in Hypertensive Patients Based (Atenolol) Treatment Program in Hypertensive Patients

with LVH (LIFE Study)with LVH (LIFE Study)

LosartanLosartan Atenolol Atenolol Goal BPs Goal BPsAchieved BP (mm Hg)Achieved BP (mm Hg) 144/82 144/82 145/82 45-50% SBP <140 145/82 45-50% SBP <140

89% DBP <9089% DBP <90

% Difference Losartan vs AtenololPrimary endpoint P Value(CV death, MI, Stroke) -13* .02•Stroke -25* .001•MI +07 NS•CV mortality -11 NS•Total mortality -10 NS•New onset diabetes -25* .001

Lancet 2002;359:1004 *Statistically significant

Percentage of Type 2 Diabetic Patients with End-Stage Percentage of Type 2 Diabetic Patients with End-Stage Renal Disease in the RENAAL StudyRenal Disease in the RENAAL Study

Losartan – therapy with ARB plus other medications; placebo – therapy with Losartan – therapy with ARB plus other medications; placebo – therapy with medications other than an ARB or ACE inhibitor. (Risk reduction, 28%; P = medications other than an ARB or ACE inhibitor. (Risk reduction, 28%; P = 0.002)0.002) Brenner BM, et al. N Engl J Med 2001;345:865Brenner BM, et al. N Engl J Med 2001;345:865

Months of Study

En

d-S

tag

e R

ena

l D

isea

se

(%)

0 12 24 36 48

30

20

10

0

Placebo

Losartan

Heart Outcomes Preventions Evaluation (HOPE) Study

Events ACE-1(Ramipril)*

Regimen that did not include an ACE-1

No. Randomized 4645 4652% Reduction in Risk - Ramipril:Other therapy

MI, Stroke, CVD 22CV death 25MI 20Stroke 31Non-CV death +3 (NS)All cause mortality 16

*10 mg/day - 62.5% remained on Rx at 4.5 years New Engl J Med 11/10/99

Relative Risk of Cardiovascular Mortality and Relative Risk of Cardiovascular Mortality and Morbidity for ACEIs vs Calcium Antagonists (Morbidity for ACEIs vs Calcium Antagonists (STOP-STOP-

2 Study2 Study))

**Significant difference.Significant difference.Hansson L et al. Lancet. 1999;354:1751-1756Hansson L et al. Lancet. 1999;354:1751-1756

En pacientes de alto riesgo

(HOPE, IRMA, IDNT, RENAAL, and LIFE),

el uso de un IECA (o un ARA) usualmente con

un diuretico) reducen eventos CV mas que un

regimen que no incluye estas medicaciones.

2003

The Antihypertensive and Lipid

Lowering Treatment to Prevent Heart

Attack Trial (ALLHAT),

Years to CHD Event0 1 2 3 4 5 6 7

Cumulative CHD Event Rate

0

.04

.08

.12

.16

.2

Number at Risk: Chlorthalidone 15,255 14,477 13,820 13,102 11,362 6,340 2,956 209 Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215 Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195

Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group

0.810.810.99 (0.91-1.08)0.99 (0.91-1.08)LL//CC

0.650.650.98 (0.90-1.07)0.98 (0.90-1.07)AA//CC

p valuep valueRR (95% CI)RR (95% CI)

ChlorthalidoneAmlodipineLisinopril

Implications of ALLHATImplications of ALLHAT

Diuretics should be the drug of choice for first Diuretics should be the drug of choice for first

step therapy of hypertension in most patients*step therapy of hypertension in most patients*

Most hypertensive patients require more than one Most hypertensive patients require more than one

drug. Diuretics should generally be part of the drug. Diuretics should generally be part of the

antihypertensive regimen. antihypertensive regimen.

*[BP levels were lower in diuretic treated*[BP levels were lower in diuretic treated patients ]patients ]

Possible Advantages of Low-Dose Combination Therapy Possible Advantages of Low-Dose Combination Therapy Compared to High-Dose MonotherapyCompared to High-Dose Monotherapy

Blood pressure response is greaterBlood pressure response is greater

Percentage of responders is higherPercentage of responders is higher

Side effects may be lessSide effects may be less

Titration to effective dose is simplified- Goal Titration to effective dose is simplified- Goal

BP achieved soonerBP achieved sooner

Adherence is improvedAdherence is improved

StrokeStroke

Combination Combination 43% 43%

Single Drug Single Drug 5% (-19 to 23) 5% (-19 to 23)

Total Stroke Total Stroke 28% 28%

Favorsactive

Favorsplacebo

Risk Reduction( 95%CI )

0.4 1.0 2.0

Hazard Ratio

Combination versus MonotherapyCombination versus Monotherapy

PROGESS Study

Combination TherapyCombination Therapy

In the LIFE trial treatment to goal In the LIFE trial treatment to goal was aggressively pursuedwas aggressively pursued

90% of patients required multiple 90% of patients required multiple medicationsmedications

Benefits of Lowering BP byBenefits of Lowering BP by

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure 50%

-12-4-5About mmHg

JNC 7 Primary Rx recommends:JNC 7 Primary Rx recommends:

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