Treating essential hypertension. The first choice is usually a thiazide diuretic

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.