blood pressure control in patients with type 2 diabetes and hypertension

R E V I E W A R T I C L E

Blood pressure control in patients with type 2 diabetes and

hypertension

JoseÂ R. GonzaÂlez-Juanatey

Cardiology Department, Hospital ClõÂnico Universitario, Santiago de Compostela, Spain

Keywords: hypertension, type 2 diabetes mellitus, treatment

Received 22 October 2000; returned for revision 20 February 2001; revised version accepted 14 February 2001

Introduction

Diabetes mellitus and systemic arterial hypertension are

two of the commonest chronic diseases in industrialized

nations, and are frequently associated. The prevalence

of hypertension is greater among patients with type 2

diabetes mellitus than in the general population, 40%

being hypertensive at age 40 years and > 60% at age

75 years [1,2]. Hypertension increases the already high

risk of micro- and macrovascular complications of type

2 diabetes mellitus, giving rise to 75% of cardiovascular

and renal complications [3]. The coincidence of hyper-

tension and diabetes mellitus appears to accelerate the

development of left ventricular hypertrophy [4], a major

contributor to cardiovascular risk, and greatly increases

the risk of stroke, transient ischaemic attacks, peripheral

vascular disease, end-stage kidney disease or blindness

[4]. These relationships justify the development of

aggressive therapeutic strategies aimed at minimizing

the impact of diabetes mellitus and hypertension on the

cardiovascular system of patients with both these

conditions.

The aim of this review is to survey current controversy

concerning target blood pressures (BP), the bene®ts of

treatment and the choice of antihypertensive drugs in

the clinical management of diabetic hypertensive pa-

tients. In particular, I discuss the possible superiority of

the new classes of antihypertensives±angiotensin-con-

verting enzyme (ACE) inhibitors and angiotensin II

antagonists (AIIAs)±over traditional agents (diuretics,

b-blockers and calcium antagonists) in the light of the

main recent studies that have approached this issue,

which of course concerns not only diabetic hypertensive

patients but hypertensive patients in general.

How Far Should Blood Pressure Be Lowered in

Hypertensive patients with Type 2 Diabetes?

It is well established that a sustained reduction in BP

signi®cantly reduces cardiovascular mortality and mor-

bidity among hypertensive patients [5] (®gure 1). Given

this, the question that immediately arises is `What

degree of BP reduction produces maximum bene®t?'

The goal of the Hypertension Optimal Treatment

(HOT) study was to determine the optimal level of BP

control and the impact of aspirin on the cardiovascular

outcome of patients with hypertension [6]. Nearly

19 000 patients were randomised to target diastolic BPs

of < 90 mm Hg, < 85 mm Hg or < 80 mm Hg, and to

either placebo or 75 mg/day of acetylsalicylic acid

(aspirin). BP goals were achieved with a calcium

antagonist (felodipine), alone or in combination with

ACE inhibitors or b-blockers. The results of the study

suggest that while diastolic BP < 80 mm Hg is optimal for

hypertensive patients with type 2 diabetes, for non-

diabetic hypertensive patients reduction to < 140/

90 mmHg is adequate. In the 1501 patients with diabetes

mellitus at the start of the study, the group with a

diastolic target of < 80 mm Hg had half as many major

cardiovascular accidents as the group with a target

of < 90 mmHg (22 vs. 45; p = 0.005), although the

difference between the actual mean diastolic pressures

in the two groups was only 4 mm Hg. When patients

with silent myocardial infarction were included the

difference was less striking, but remained signi®cant

(p = 0.045). By contrast, in the whole sample of nearly

19 000 patients, the stricter diastolic target reduced risk

by only 7%. The incidence of stroke among diabetic

patients was also reduced by setting the stricter diastolic

Correspondence:

JoseÂ RamoÂn GonzaÂlez-Juanatey, Cardiology Department, Hospital ClõÂnico Universitario, TravesõÂa de A Choupana s/n, 15706 Santiago

de Compostela, Spain.

E-mail:

[email protected]

| RA

ã 2002 Blackwell Science Ltd Diabetes, Obesity and Metabolism, 4, 2002, 81±88 | 81

target, being about 30% smaller in the < 80 mm Hg

group than in the < 90 mm Hg group, and so was the

incidence of cardiovascular mortality, which was

signi®cantly lower in the < 80 mm Hg group than in

either the < 90 mm Hg or the < 85 mm Hg groups

(p = 0.016). These results strongly support the desirabil-

ity of aiming for compliance with stringent BP limits in

hypertensive patients with type 2 diabetes mellitus.

In a study carried out in association with the United

Kingdom Prospective Diabetes Study (UKPDS 38) [7],

patients with both hypertension and type 2 diabetes

mellitus were randomly assigned to either tight BP

control (target < 150/85 mm Hg; n = 758) or looser control

(target < 180/105 mm Hg; n = 390). Captopril or atenolol

were assigned randomly upon entry into the study, and

for achievement of BP targets were accompanied if

necessary by a diuretic (furosemide), nifedipine,

methyldopa or prazosin. At the end of the study, the

mean arterial pressures in the tight and loose groups

were 144/82 and 154/87 mm Hg, respectively. Relative

to the loose group, the tight group had a 32% lower risk

of diabetes-related death (p = 0.019), a 66% lower risk of

developing heart failure within 8.5 years, a 44% lower

risk of stroke (p = 0.013), and a 37% lower risk of

microvascular complications (p = 0.009), the latter due

mainly to lower risk of retinal photocoagulation

(table 1). After 9 years' follow-up, the proportion of

patients in whom retinopathy had worsened by two

stages was also 34% lower in the tight group than in the

loose group, and mean loss of visual acuity (as measured

by the Early Treatment of Diabetic Retinopathy Study

Chart) was 47% less than in the loose group (p = 0.004).

It is noteworthy that about 30% of the tight group

needed three antihypertensives to achieve their BP

target; this is in keeping with the ®nding that in

INSIGHT (the International Nifedipine GITS Study:

Intervention as a Goal in Hypertension Treatment)

patients with diabetes were the most recalcitrant,

requiring second and third drugs, respectively, 40%

and 100% more frequently than non-diabetics [8].

The above results highlight the desirability of strict BP

control in hypertensive diabetics. The targets recom-

mended by JNC VI and WHO ISH are < 130/85 mm Hg for

hypertensive diabetics and < 125/75 mm Hg for hyper-

tensive diabetics with proteinuria > 1 g/day [9,10].

Although the evidence in support of exactly these limits

is not absolutely conclusive, the results of the HOT [6]

and UKPDS [7] studies undoubtedly prove that in

diabetic hypertensive patients the maintenance of low

BP signi®cantly reduces the risk of cardiovascular

complications.

A recent formal cost-effectiveness analysis compared

the costs and potential bene®ts of BP pressure goals of

< 140/90 and < 130/85 mm Hg [11]. Using published

data, a 24-cell computer model was parameterized with

the costs, relative risks and age-speci®c baseline

incidences of death and of non-fatal stroke, myocardial

infarction, heart failure and end-stage renal disease. For

a 60-year-old diabetic patient with hypertension, treat-

ment to achieve the stricter BP goal increased life

expectancy by 0.48 years and lowered lifetime medical

costs by US $1450 (1996) in comparison with treatment

to achieve the laxer goal. Thus, any incremental

treatment for 60-year-olds that lowered BP from < 140/

Fig. 1 Overview of randomised trials of antihypertensive

treatment (n = 52 348; 5-year follow-up). Systolic blood pressure

difference = 10±12 mm Hg; diastolic blood pressure

difference = 5±6 mm Hg. h = non-fatal events; j = fatal events;

T = treatment; C = control. Reduction in odds (%): stroke = 39%

(SE 4); coronary heart disease = 16% (SE 4); vascular

deaths = 21% (SE 4); all other deaths = 2% (SE 5). p-values:

stroke, coronary heart disease and vascular deaths = < 0.001; all

other deaths = > 0.5. CHD = coronary heart disease. (Adapted

from [5]).

Table 1 United Kingdom Prospective Diabetes Study (UKPDS):

results

Risk reduction

(%) p

Intensive glucose control reduces risk of:

Any diabetes-related endpoints 2 0.029

Diabetes-related deaths 10 0.340

Microvascular endpoints 25 0.010

Tight BP control* with captopril- or atenolol-based therapy

reduces risk of:

Any diabetes-related endpoints 24 0.005

Diabetes-related deaths 32 0.019

Stroke 44 0.013

Microvascular endpoints 37 0.009

BP = blood pressure.

*Mean BP achieved = 144/82 vs. 154/87 mm Hg.

(Data adapted from [7,30]).

RA | BP control in patients with type 2 diabetes JoseÂ R. GonzaÂ lez-Juanatey

| Diabetes, Obesity and Metabolism, 4, 2002, 81±88 ã 2002 Blackwell Science Ltd82

90 to < 130/85 mm Hg for < $414/year would reduce

long-term costs.

It may be concluded that for diabetics in general,

BP of < 130/85 mm Hg constitutes a valid target, and

that this goal is more cost-effective than many other

frequently recommended strategies. For diabetics with

nephropathy (proteinuria > 1 g/day), the JNC VI guide-

lines recommend BPs < 125/75 mm Hg, several studies

having shown that strict BP control reduces protei-

nuria and the rate of advance of diabetic renal

disease [12,13]. Again, it should be emphasized that

these recommendations (both the targets for diabetics

with nephropathy and the targets for those without)

are to be understood as orientative rather than

absolutely achieved, either as regards the systolic

target of 130 mm Hg for diabetics in general or the

targets set for nephropathic diabetics. The HOT

results [6], however, suggest that for diabetics in

general the diastolic target might advantageously be

even stricter, < 80 mm Hg instead of < 85 mm Hg.

Antihypertensive Therapy

The question arises as to what kind of drug best prevents

cardiovascular and renal complications in hypertensive

patients with type 2 diabetes mellitus. This question is

in part being tackled by the still un®nished study

ALLHAT (Antihypertensive and Lipid-Lowering Treat-

ment to Prevent Heart Attacks), which includes about

16 000 hypertensive diabetics randomly assigned to

treatment with the ACE inhibitor lisinopril, the a-

blocker doxazosin, the dihydropyridine calcium antago-

nist amlodipine or the diuretic chlorthalidone with a

view to determining the effects of these various drug

classes on the risk of non-fatal myocardial infarction or

fatal coronary heart disease [14]. Recently the doxazosin

arm was prematurely discontinued due to an increase in

cardiovascular complications (particularly heart failure)

during the follow-up in comparison with the patients

treated with diuretics [15]. However, even when the

class of antihypertensive that is most effective for these

purposes in the hypertensive diabetic has been identi-

®ed, it should be borne in mind that for these patients

strict BP control frequently requires the use of multiple

drugs. In the UKPDS [7], 29% of hypertensive patients

with type 2 diabetes mellitus needed three or more

drugs even to achieve an average BP of 144/82 mm Hg

(considerably higher than the JNC VI recommended

target of < 130/85 mm Hg), and similar ®gures were

found in the HOT study [8].

Table 2 Results of the Systolic Hypertension in the Elderly Programme (SHEP) and the Systolic Hypertension in Europe Trial

(Syst-Eur) in diabetic and non-diabetic hypertensive patients

Diabetics Non-diabetics

SHEP Syst-Eur SHEP Syst-Eur

n (%) 590 (12.3) 492 (10.5) 4149 (87.7) 4203 (89.5)

Mean BP reduction*

SBP (mm Hg) ± 9.8 ± 8.6 ± 12.5 ± 10.3

DBP (mm Hg) ± 2.2 ± 3.3 ± 4.1 ± 4.6

Risk in placebo group²

Total mortality 35.6 45.1 21.8 21.6

CV endpoints 63.0 55.0 36.8 28.9

Stroke 28.8 26.6 15.0 12.3

Coronary events 32.2 23.1 15.2 12.4

Change with active treatment³

Mortality ± 26 (± 54, 18) ± 64 (± 83, ± 25) ± 15 (± 32, 6) ± 18 (± 40 13),

All CV endpoints ± 34 (± 54, ± 6) ± 68 (± 84, ± 35) ± 34 (± 45, ± 21) ± 30 (± 48, ± 8)

Stroke ± 22 (± 55, 34) ± 86 (± 96, ± 58) ± 38 (± 54, ± 17) ± 39 (± 60, ± 7)

Coronary events ± 56 (± 75, ± 23) ± 58 (± 87, 37) ± 19 (± 38, 5) ± 22 (± 47, 17)

CV = cardiovascular; DBP = diastolic blood pressure; SBP = systolic blood pressure.

*The mean effect of active treatment on blood pressure was corrected for baselines and placebo.

²Rate expressed as events/100 patient-years.

³The changes with active treatment were calculated by Cox regression with adjustments for sex, age, smoking, DBP and SBP at baseline,

electrocardiographic abnormalities (SHEP) or previous CV complications (Syst-Eur) at baseline, and race (SHEP) or residence in Western

Europe (Syst-Eur).

JoseÂ R. GonzaÂ lez-Juanatey BP control in patients with type 2 diabetes | RA


Dihydropyridine Calcium-Channel Blockers

In recent years the results of a number of studies have

thrown doubt on dihydropyridine calcium antagonists

for treatment of hypertensive diabetics, suggesting that

these drugs perform signi®cantly worse than ACE

inhibitors as regards reduction of the risk of myocardial

infarction or other vascular accidents. On the other

hand, studies with longer follow-up periods have found

that long-acting calcium antagonists, alone or in combi-

nation with diuretics, ACE inhibitors or b-blockers, are

bene®cial to patients with hypertension and diabetes

mellitus.

The primary objective of the double-blind Appropri-

ate Blood Pressure Control in Diabetics trial (ABCD) was

to compare the advance of diabetic nephropathy in 480

normotensive and 470 hypertensive patients randomly

assigned to treatment with enalapril or nisoldipine [16].

The hypertensive diabetics were administered either

nisoldipine (10±60 mg/day) plus enalapril placebo, or

enalapril (5±40 mg/day) plus nisoldipine placebo. After

67 months the Data and Safety Monitoring Board

suspended nisoldipine treatment of hypertensive pa-

tients because of a signi®cant difference between

nisoldipine and enalapril as regards the incidence of

myocardial infarct (25 and 5 in the nisoldipine and

enalapril hypertensive groups, respectively, giving a

relative risk of 5.5 for nisoldipine vs. enalapril). The real

signi®cance of this difference has nevertheless been

questioned on the grounds that the trial was not

designed to detect differences in incidence of infarct,

and that the enalapril group had a more complete

treatment, receiving more diuretics and b-blockers and

suffering fewer suspensions of treatment than the

nisoldipine group [17,18].

The Fosinopril vs. Amlodipine Cardiovascular Event

Trial (FACET) [19] randomly assigned hypertensive

patients with type 2 diabetes mellitus to treatment with

fosinopril (20 mg/day; n = 130) or amlodipine (10 mg/

day; n = 140), although both drugs were given when BP

was not successfully controlled with just one (n = 110).

The primary objective of the trial was to compare the

two treatments as regards their effects on serum lipids,

control of diabetes and kidney function. In the amlodi-

pine-only group 17 cases of myocardial infarct or ®rst-

appearance angina occurred, in the fosinopril-only

group there were seven, and in the combined group

three. The risk of myocardial infarct, stroke or hospita-

lization for angina was reported as signi®cantly lower

among patients initially assigned to fosinopril than

among those initially assigned to amlodipine (14/189 vs.

27/191). However, like the ABCD trial, FACET is open to

objections: it was a single-centre study with intervals of

6 months between follow-up examinations; it was not

designed to evaluate differences in the incidence of

cardiovascular complications; 58 of the patients initially

assigned to fosinopril (31%) and 50 of those initially

assigned to amlodipine (26%) eventually received both

drugs; and at the beginning of the study microalbumi-

nuria was signi®cantly greater in the amlodipine group

than in the fosinopril group (24 6 1 as against 20 6 1 mg/

min).

The results of the ABCD trial and FACET are the main

arguments against the use of dihydropyridine calcium

antagonists to treat hypertensive diabetics.

In the Systolic Hypertension in Europe study (Syst-

Eur) [20], 4695 isolated systolic hypertension patients

aged > 60 years were randomly assigned to placebo or

active treatment (generally nitrendipine (10±40 mg/day).

However, if necessary for BP control, this drug was

combined with or replaced by enalapril (5±20 mg/day),

hydrochlorothiazide (12.5±25.0 mg/day), or both. Active

treatment reduced the overall incidence of fatal and

non-fatal target outcomes by 31% (p < 0.001). Among

the492 patients with both hypertension and diabetes

mellitus (10.5%), BP reduction after correction for

placebo effects was similar to that of non-diabetics,

8.6/3.9 mm Hg as against 10.3/4.6 mm Hg [21], but the

diabetic group showed signi®cantly greater reductions

in total mortality (p = 0.04), cardiovascular mortality

(p = 0.02) and the overall incidence of cardiovascular

target outcomes (p = 0.01). In the diabetic group, active

treatment reduced total mortality by 55%, cardiovascu-

lar mortality by 76%, the overall incidence of cardio-

vascular target outcomes by 69%, stroke (fatal or

Table 3 Relative risk of cardiovascular complications in 572

patients with diabetes at baseline in the Captopril Prevention

Project*

Captopril vs. p

conventional therapy²

(relative risk)³

Composite endpoint (primary)* 0.6 (0.4±0.9) 0.02

Fatal cardiovascular events 0.5 (0.2±1.1) 0.09

Stroke (fatal and non-fatal) 1.0 (0.6±1.9) 0.95

Myocardial infarction

(fatal and non-fatal) 0.3 (0.2±0.7) 0.01

All fatal events 0.5 (0.3±1.0) 0.03

All non-fatal events 0.7 (0.5±1.0) 0.03

*Fatal and non-fatal stroke or myocardial infarction.

²Conventional therapy consisted of diuretics or b-blocking agents.

³Adjusted for age, sex, systolic blood pressure and previous

antihypertensive therapy.



non-fatal) by 73%, and the overall incidence of cardiac

target outcomes by 63%.

Similar results were obtained for the 98 diabetic

patients (4.1%) in the Systolic Hypertension in China

study (Syst-China) [22]. In this study, patients were

randomly assigned to placebo or active treatment

(nitrendipine, 10±40 mg/day; with or without captopril,

12.5±50.0 mg/day; and/or hydrochlorothiazide, 12.5±

50 mg/day). Within 2 years, BP after correction for

placebo effects had fallen by 6.0/4.7 mm Hg in the

diabetic group and by 9.3/3.1 mm Hg in the non-diabetic

group. Active treatment reduced the relative risk of

death by 59% and 36% in the diabetic and non-diabetic

groups, respectively; the relative risk of cardiovascular

mortality by 57% and 33%, respectively; and the overall

relative risk of cardiovascular target outcome by 74%

and 34%, respectively.

Similarity of design allows the Syst-Eur results [20] to

be compared directly with those of the Systolic

Hypertension in the Elderly Programme (SHEP) [23],

in which the active treatment was chlorthalidone (12.5±

25.0 mg/day) with or without atenolol (25±50 mg/day) or

reserpine (0.05±0.10 mg/day). The active treatment

groups of the two studies achieved similar BP reduc-

tions, but in the hypertensive diabetic groups the

dihydropyridine nitrendipine achieved signi®cantly

greater reductions in cardiovascular complications and

total and cardiovascular mortalities than did the

thiazide chlorthalidone (table 2).

Diuretics

The above difference between the SHEP and Syst-Eur

results is in keeping with the ®ndings of a number of

studies that have concluded that diuretics reduce

sensitivity to insulin in hypertensive diabetics, and that

at high doses they thereby cause deterioration of glucose

control, alter lipid levels and increase the risk of

diabetic kidney disease [24±26], although these altera-

tions are less likely at low doses (e.g. 6±25 mg of

hydrochlorothiazide/day [23]. Although INSIGHT found

no differences between the sustained release dihydro-

pyridine calcium antagonist nifedipine GITS (30±60 mg/

day) and a combination of diuretics (25±50 mg/day of

hydrochlorothiazide and 2.5±5.0 mg/day of amiloride)

as regards their effects on the prognosis of high-risk

hypertensives, diabetes mellitus developed signi®cantly

more often in the group receiving diuretics [27]. By

contrast, however, a prospective study of 12 550 initially

non-diabetic subjects (45±64 years old) [28] found that

among the 3804 with hypertension, those taking

thiazide diuretics (n = 458) were at no greater risk of

developing diabetes mellitus than those who were not

receiving any antihypertensive therapy (relative hazard

0.91, 95% con®dence interval 0.73±1.13).

ACE Inhibitors

The validity of ACE inhibitors for treatment of hyper-

tensive diabetics is shown by the results of the Heart

Outcomes Prevention Evaluation study (HOPE) and of

its microalbuminuria, cardiovascular and renal out-

comes substudy (MICRO-HOPE) [29]. As part of HOPE,

3577 diabetic patients > 55 years who had suffered a

prior cardiovascular accident or exhibited some other

cardiovascular risk factor, but who had no proteinuria,

heart failure or depression of left ventricular ejection

fraction and were not receiving ACE inhibitors, were

randomly assigned to treatment with ramipril (10 mg/

day) or placebo and to vitamin E or placebo in

accordance with a 2 3 2 factorial design. The primary

outcome was the disjunctive combination myocardial

infarction or stroke or cardiovascular death. Overt

nephropathy was a main outcome in a substudy. HOPE

was terminated after 4.5 years by the Data and Safety

Monitoring Board because by that time the superiority of

ramipril to placebo had already been established: mean

systolic BP had fallen by 1.9 mm Hg from 141.7 to

139.8 mm Hg in the ramipril group but had risen by

0.6 mm Hg from 142.3 to 142.9 mm Hg in the placebo

group (p = 0.0002); mean diastolic BP had fallen by

3.3 mm Hg from 80.0 to 76.7 mm Hg in the ramipril

group as against a fall of 2.3 mm Hg from 79.3 to 77.0 mm

Hg in the placebo group (p = 0.008); and ramipril

reduced the risk of the primary outcome by 25%

(p = 0.0004) with or without adjustment of the data for

change in BP.

As regards comparison of ACE inhibitors with other

classes of antihypertensive, the UKPDS found that the

ACE inhibitor captopril was no better than the b-blocker

atenolol in lowering the risk of macro- and microvas-

cular accidents among 758 hypertensive patients with

type 2 diabetes mellitus [30]. Although the differences

were not statistically signi®cant, the b-blocker group

had fewer cases of heart failure, fewer cases of sudden

death (perhaps because of the well-known ef®cacy of b-

blockers against ventricular arrhythmia), and fewer

amputations due to peripheral vascular disease, the

incidence of which, as judged on the basis of absent foot

pulses or Doppler BP measurements, was the same in

both groups [31]. Changes in albuminuria and serum

creatinine during the 9-year course of the study were the

same in both drug groups, and although glycated

haemoglobin (HbA1c) was signi®cantly higher in the b-



blocker group during the ®rst 4 years, there was no

signi®cant intergroup difference in this respect there-

after. It is possible, however, that the absence of

signi®cant prognostic differences between the two

treatments may have been due to the limited ef®cacies

of both: although BP fell from 159/94 to 144/83 mm Hg

in the captopril group and from 159/93 to 143/81 mm Hg

in the atenolol group, in both groups the BPs of most

patients remained in the hypertensive range.

By contrast, almost the opposite conclusion emerges

from the results of the Captopril Prevention Project

(CAPPP) [32]. In this study, 10 985 patients were

randomly assigned to treatment with captopril or to

conventional treatment with diuretics and/or b-block-

ers. After 6 years the two groups showed similar

incidences of cardiovascular accidents, although as in

the UKPDS this negative result may have been due to the

BP of most patients still being in the hypertensive range

at the end of the study (in spite of mean BP having fallen

from 167/104 to 152/89 mm Hg in the captopril group

and from 163/101 to 149/87 mm Hg in the conventional

treatment group). However, the incidence of type 2

diabetes mellitus was lower with captopril than with

conventional treatment (p = 0.039), and among the 572

hypertensive diabetics cardiovascular morbidity and

mortality were signi®cantly lower with captopril than

with conventional antihypertensive patients (p = 0.019)

(table 3), although the two treatment groups did not

differ signi®cantly as regards the incidence of stroke

among hypertensive diabetics.

Taken together, the above data suggest that the

cardiovascular protection afforded by ACE inhibitors

may be comparatively rather more effective for hyper-

tensive diabetics than for hypertensive patients in

general, but there is no conclusive evidence of their

superiority or inferiority to other groups of antihyper-

tensive patients [33]. On the contrary, the Swedish Trial

in Old Patients with Hypertension 2 (STOP 2) found no

signi®cant differences between conventional antihyper-

tensives (b-blockers and diuretics) and newer drugs

(ACE inhibitors and calcium antagonists) as newer

drugs (ACE inhibitors and calcium antagonists) as

regards their effects on cardiovascular mortality and

morbidity in elderly patients, either in the whole study

group or in the 719-member diabetic subgroup [34].

Final Remarks

According to a recent meta-analysis of randomized

studies of calcium antagonists, these drugs are inferior

to other types of antihypertensive drugs as ®rst-line

agents for reduction of risk with regard to several major

complications of hypertension [35]. On the other hand,

another recent meta-analysis of randomized trials found

no group of antihypertensive drugs to be clearly superior

to others [36]. Both these studies concerned hyperten-

sive patients in general, but in this review we have seen

that the situation is much the same when only diabetic

hypertensive patients are considered: at the present time

the body of available evidence does not appear to point

to any one group of antihypertensive drugs as unques-

tionably or generally superior to the others. Conse-

quently, except when the use of a particular group is

speci®cally indicated or debarred by the patient's

condition or the appearance of adverse side-effects,

reduction of the risk of cardiovascular complications in

hypertensive diabetics should at present not be sought

by reliance on a particular drug group, but through the

use of whatever drugs may prove effective for maintain-

ing BP at levels known to ensure a lower risk of such

complications. In most cases, achievement of this BP

goal requires a combination of two or more drugs.

Although current data suggest that one of these should

probably be an ACE inhibitor, low doses of thiazide

diuretics, sustained-release dihydropyridine calcium

antagonists and cardioselective b-blockers are also

bene®cial.

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