Angiotensin II antagonists: efficacy, duration of action, comparison with other drugs

Abstract

The benefits of anti-hypertensive drug treatment have been established by clinical trials demonstrating significant reductions in cardiovascular morbidity and mortality. Thiazide diuretics predominated in these trials but it is reaasonable to conclude that the benefits were attributable to the blood pressure (BP) reduction per se and not to specific pharmacological characteristics. Furthermore, it can be calculated that even greater benefits would probably have accrued if the magnitude of the BP reduction had been greater. On first principles, therefore, the basic requirement for any anti-hypertensive drug is confirmation of its ability to reduce BP. The angiotensin II antagonists constitute an important new class of drug, with a low incidence of adverse effects, but early studies with the prototype, losartan, have raised some doubts about its anti-hypertensive ‘potency’ in the clinical setting. For example, in several different comparative studies there were consistently lesser BP reductions with losartan compared to enalapril. This applied to both the trough and peak BP reductions. Furthermore, dose-response relationships have not always been clearly defined: for example, in one study diastolic BP reductions (trough) fell in the range 4.1 to 4.8 mm Hg with 50, 100 and 150 mg losartan. Although the preliminary results with newer angiotensin II antagonists suggest that they may have greater efficacy, there is only limited information about the definitive identification of the clinically relevant dose ranges for many of these drugs.