Perindopril versus angiotensin II receptor blockade in hypertension and coronary artery disease: implications of clinical trials

Abstract

The renin-angiotensin-aldosterone system (RAAS) is now known to play a key role in the pathogenesis of hypertension and a range of other cardiovascular diseases. Two groups of drugs, the ACE inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) have been developed with the aim of improving clinical outcomes by regulating the RAAS in patients with cardiovascular disease. Initial assumptions were that these two drug types might be interchangeable, but ongoing research has revealed differences between them in terms of pharmacology and outcomes in clinical trials. Although both groups of drugs lower blood pressure, studies of the ACE inhibitor perindopril have revealed preservation of beneficial vascular and endothelial effects mediated by bradykinin and nitric oxide. The selective blockade exerted by ARBs is not associated with these effects. Furthermore, examination of clinical endpoints in major clinical trials has provoked discussion about outcomes comparing ACE inhibitors and ARBs, with recent debate focusing on the incidence of myocardial infarction (MI) in patients receiving these agents. Whether there is an actual difference in protection from MI remains unresolved, although available data confirm the benefit and safety of ACE inhibitors, in particular perindopril, for myocardial protection.