New Opportunities in Cardiovascular Patient Management: A Survey of Clinical Data on the Combination of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) differ in their actions on the renin-angiotensin-aldosterone system (RAAS). ACE inhibitors prevent the formation of angiotensin II, although angiotensin II may still be generated by alternative pathways. However, ACE inhibitors interrupt bradykinin breakdown, which in turn potentially enhances nitric oxide and prostacyclin mechanisms. In contrast, ARBs selectively prevent the binding of angiotensin II to the angiotensin type 1 (AT1) receptor while leaving the potentially beneficial effects of the AT2 receptor unaffected. The supposition is that dual blockade of the RAAS effectively overcomes the harmful effects of angiotensin II mediated by the AT1 receptor while offering the additional effects of the ACE inhibitor. This concept was first evaluated clinically more than a decade ago in small-scale studies that were not sufficiently powered to conclusively demonstrate benefits from dual blockade. Subsequently, larger-scale trials have been conducted to determine the effects of a combination of an ACE inhibitor and an ARB in combating the effects of angiotensin II at different stages of cardiovascular and renal disease. This review explores these data in areas, such as hypertension, renal disease, and cardiovascular disease, and draws on this preliminary evidence to support the rationale for the Ongoing Telmisartan Alone in Combination with Ramipril Global Endpoint Trial (ONTARGET) program, which aims to fully explore the clinical end points and effects of dual RAAS blockade in patients at high risk for cardiovascular outcomes.