ACE Inhibition in Hypertension

Abstract

Ongoing developments in our understanding of cardiovascular disease, together with the introduction of new drugs to treat these conditions, has led to much debate over the optimal management of hypertension. The ALLHAT study showed no major differences in cardiovascular outcome among three major classes of antihypertensive drugs. Indeed, large meta-analyses have substantiated this view, and most experts would agree that BP reduction matters more than the choice of antihypertensive agent. However, recently published data from the ASCOT-BPLA trial for hypertensive patients at moderate risk of cardiac events have caused some experts to re-evaluate this view. The recent Blood Pressure Lowering Treatment Trialists' Collaboration publication confirmed this change. In the ASCOT-BPLA trial, antihypertensive therapy based on amlodipine+perindopril significantly reduced total and cardiovascular mortality as well as other clinically relevant outcomes in comparison with a traditional strategy based on atenolol and a thiazide diuretic, despite both regimens producing nonsignificantly different reductions in brachial BP. These findings suggest that amlodipine/perindopril may exert a beneficial effect by acting on other parameters such as central BP or BP variability. ACE inhibitors have been shown to have antiatherosclerotic and antithrombogenic effects, to improve endothelial dysfunction, and to prevent cardiac remodeling in patients with coronary heart disease. In this regard, perindopril, which has relatively high affinity for ACE and true 24-hour duration of action, is one of the most extensively studied ACE inhibitors. More recent data suggest that ACE inhibitors reduce arterial stiffness, an independent risk factor for cardiovascular events, and have a beneficial effect on central aortic BP, thus providing a possible explanation for the findings of ASCOT-BPLA and confirming that ACE inhibitors are an appropriate first choice for patients with hypertension.