Evidence based management of hypertension: What are the elements of good treatment for hypertension?

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Benefits and harms of antihypertensive drug treatment General benefits Many large randomised placebo controlled trials consistently show that antihypertensive drug treatment decreases the risk of fatal and non-fatal stroke, cardiac events, and death in men and women with systolic or diastolic hypertension,1–3 without adverse effect on quality of life, which may even be improved.4 People at greater cardiovascular risk when they start treatment, such as elderly patients with other relevant risk factors, derive the most absolute benefit from drug treatment. Specific antihypertensive drugs as first line agents It is not clear whether the benefits of specific antihypertensive drugs come from their direct effects on raised blood pressure or whether they act by various other multiple indirect actions. It is difficult to assess effects of particular agents, because most large trials have used a stepped care approach in which a second or third drug is added when the first choice does not reduce blood pressure to target level. Evidence relating to first line options is provided below and in the table. View this table: In this window In a new window First line antihypertensive drugs for people with hypertension Thiazide diuretics—Many large hypertension trials have compared hydrochlorothiazide, chlorthalidone, or a combination of a thiazide and a potassium-sparing agent (such as amiloride or triamterene) with placebo or no drug treatment. Both low and high dosages of thiazide decrease rates of stroke and death; but only low dosage regimens reduce coronary artery disease.5 Several different thiazides are all apparently effective, which suggests that this is a class effect. βBlockers—Systematic reviews and meta-analyses of several randomised trials compare β blockers as first line antihypertensive agents with placebo.6–10 The data are complicated: in some trials as many as 70% of participants also receive diuretics; in others large numbers of participants cross over to other regimens. Nevertheless the data suggest, but do not prove, that β blockers reduce strokes but not coronary artery disease or death. For stroke, estimates of relative risk reductions of β blockers compared with placebo range from 0 to 0.41. 6 7 9 10 β Blockers are a heterogeneous class of agents with varying degrees of cardioselectivity and variable intrinsic sympathomimetic activity; and it is doubtful whether the cardiovascular benefits of different cardioselective β blockers represent a class effect. Angiotensin converting enzyme inhibitors—One large randomised placebo controlled trial has shown that the angiotensin converting enzyme inhibitor ramipril reduces cardiovascular events by 22% (relative risk 0.78; 95% confidence interval 0.70 to 0.86) and death by 16% in people at high risk.11 About half the trial participants had hypertension; about half had a history of myocardial infarction; and about 40% were taking β blockers. Reductions in relative risk for cardiovascular events in hypertensive patients were equal or greater than the effect in non-hypertensive patients. A recent overview of four randomised placebo controlled trials in patients, most of whom had coronary heart disease, showed that angiotensin converting enzyme inhibitors decreased strokes by 30% (15% to 43%) and coronary heart disease by 20% (11% to 28%).12 Calcium channel blockers—One large randomised trial compared a long acting preparation of the dihydropyridine calcium channel blocker nisoldipine with placebo in people aged 60 or more with isolated systolic hypertension.13 Rates of cardiovascular events with active treatment were reduced by 31% (14% to 45%) compared with placebo. Calcium channel blockers are a heterogeneous class of agents with various postulated mechanisms of action and they may not have class effects in hypertensive patients. Aims of treatment Decrease the cardiovascular risk associated with hypertension Decrease the risk from coexisting cardiovascular risk factors Improve quality of life and encourage a healthy lifestyle Choose therapeutic agents likely to do more good than harm given each patient's social circumstances, preferences, coexisting medical conditions, and risk factors Minimise the adverse effects and inconveniences from what you prescribe α Agonists and α blockers—No large randomised trials have compared clinical outcomes of first line treatment with either α agonists, such as clonidine, or α blockers, such as terazosin or doxazosin, with placebo. Comparisons of different antihypertensive agents Angiotensin converting enzyme inhibitors, diuretics, diuretics with β blockers, and calcium channel blockers—One open long term trial in 6600 patients aged 70 to 84 reported no differences in control of blood pressure or in cardiovascular morbidity or mortality among people randomised to receive conventional treatment with diuretics, alone or with β blockers, compared with calcium channel blockers (felodipine or isradipine), and with angiotensin converting enzyme inhibitors (enalapril or lisinopril).14 A single blind long term trial in 10 985 patients aged 25-66 reported that the angiotensin converting enzyme inhibitor captopril was not more effective than conventional treatment (diuretics or β blockers) in reducing cardiovascular morbidity or mortality,15 but these results were inconclusive because a flaw in the randomisation process resulted in unbalanced groups. Two additional smaller trials compared either nisoldipine with enalapril or amlodipine with fosinopril in hypertensive patients with type 2 diabetes. 16 17 They found that angiotensin converting enzyme inhibitors and calcium channel blockers were equally effective in reducing blood pressure, but calcium channel blockers were associated with a twofold to fivefold increase in cardiovascular events compared with angiotensin converting enzyme inhibitors....

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