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ARBs Challenge Standard Antihypertensive Treatment

This study addressed whether angiotensin-II-receptor blockers have clinical benefits beyond BP lowering in hypertensive patients.

A decade ago, beta-blockers and diuretics were considered the most effective preventive drug therapies in hypertensive patients. Since then, blocking angiotensin-II has been shown to reverse left-ventricular hypertrophy (LVH). Might angiotensin-II-receptor blockers (ARBs), therefore, have clinical benefits that go beyond lowering blood pressure?

In this manufacturer-funded, double-blind trial, 9193 patients with hypertension and ECG signs of LVH were randomized to receive the ARB losartan or the beta-blocker atenolol (mean daily doses, 82 mg and 79 mg, respectively). More than half of both groups received concomitant hydrochlorothiazides, but no patients took ACE inhibitors, other ARBs, or other beta-blockers.

During follow-up (mean, 4.8 years), incidence of the primary composite endpoint (cardiovascular death, MI, or stroke) was lower with losartan than with atenolol (11% vs. 13%, P=0.021), mainly because stroke incidence was 25% lower with losartan. MI incidence was similar in the 2 groups, but trends toward lower cardiovascular and all-cause mortality were found with losartan. Despite comparable BP lowering with the 2 drugs, LVH regressed more with losartan than with atenolol. New-onset diabetes was less common with losartan. Losartan was also better tolerated and caused fewer study dropouts. In a prespecified subgroup of 1195 diabetics, losartan fared significantly better than atenolol regarding the primary composite endpoint and regarding all-cause mortality, cardiovascular mortality, and admission for heart failure.

Comment: In high-risk hypertensive patients, losartan provided at least as much cardioprotection as -- and more stroke protection than -- atenolol, whether or not either drug was used with a low-dose hydrochlorothiazide. Losartan also had fewer side effects. On the basis of these findings, the editorialists argue that ARBs seem to provide cardioprotection beyond BP lowering and ought to underlie any antihypertensive treatment strategy. Although ACE inhibitors have not yet been compared directly with ARBs for this indication, ACE inhibitors are likely to achieve similar effects at lower cost.

— Beat J. Meyer, MD

Published in Journal Watch Cardiology May 17, 2002

Citation(s):

Dahlöf B et al. for the LIFE study group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002 Mar 23; 359:995-1003.

• Medline abstract (Free)

Lindholm LH et al. for the LIFE study group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002 Mar 23; 359:1004-10.

• Medline abstract (Free)

Brunner HR and Gavras H. Angiotensin blockade for hypertension: A promise fulfilled. Lancet 2002 Mar 23; 359:990-2.

• Medline abstract (Free)