We concluded in 2004 that the first-choice treatment for
hypertension in adults was single-agent
therapy with the
thiazide diuretic chlortalidone or, when this
drug is not available, the
thiazide diuretic hydrochlorothiazide. As of early 2014, does evidence challenge this choice in adults without diabetes or cardiovascular or renal disease? To answer this question, we reviewed the available evidence, using the standard Prescrire methodology. The current treatment threshold for hypertensive adults without diabetes or cardiovascular or renal disease is blood pressure above 160/100 mmHg or 160/90 mmHg, with some uncertainty over which diastolic threshold should be used. Apart from certain
diuretic-based combinations, the use of combinations of
antihypertensive drugs as first-line
therapy has not been evaluated in terms of the complications of
hypertension. A number of systematic reviews with meta-analyses of data on
tens of thousands of patients have compared the main classes of
antihypertensive drugs against each other and against placebo. Compared with placebo, only low-dose
thiazide diuretics and
angiotensin-converting enzyme (
ACE) inhibitors have been shown to reduce all-cause mortality in hypertensive patients. They prevented about 2 to 3 deaths and 2
strokes per 100 patients treated for 4 to 5 years. Several systematic reviews concluded that neither
calcium-channel blockers,
ACE inhibitors nor beta-blockers are more effective than
thiazide diuretics in reducing mortality or the incidence of
stroke. The efficacy of the
thiazide diuretic chlortalidone is supported by the highest-level evidence, from three comparative clinical trials versus placebo, an
ACE inhibitor, or a
calcium-channel blocker, in more than 50 000 patients. In one of these trials,
chlortalidone was superior to the
ACE inhibitor lisinoprilin preventing
stroke. It was also superior to the
calcium-channel blocker amlodipine in preventing
heart failure. The effect of
hydrochlorothiazide, combined with
amiloride or
triamterene, on cardiovascular morbidity and mortality has been demonstrated in three comparative clinical trials versus placebo, a beta-blocker, or a
calcium-channel blocker.
Hydrochlorothiazide appeared more effective than the beta-blocker
atenolol in reducing the incidence of coronary events. The addition of a
potassium-sparing
diuretic (
amiloride or
triamterene) to first-line
hydrochlorothiazide therapy has not been demonstrated to provide clinical benefit. The evaluation of
indapamide, another
thiazide diuretic, is less convincing. Since no head-to-head trials have been conducted, there is no evidence that it is more effective than
chlortalidone or
hydrochlorothiazide. None of the
antihypertensive drugs appears to have a better overall adverse effect profile than the others.
Thiazide diuretics can provoke hyperglycaemia and diabetes, although this does not reduce their efficacy in the prevention of cardiovascular events. As of early 2014, the first-choice treatment for
hypertension in nondiabetic adults without cardiovascular or renal disease should be
chlortalidone. If
chlortalidone is not available, it appears reasonable to choose another
thiazide diuretic,
hydrochlorothiazide, possibly combined with
amiloride or
triamterene. When a
diuretic cannot be used, it is better to choose an
ACE inhibitor:
captopril,
lisinopril or
ramipril.