Reducing cardiovascular risk by blockade of the renin-angiotensin-aldosterone system

Many factors contribute to the overall risk of cardiovascular disease (CVD) in a given patient. Activation of the renin-angiotensin-aldosterone system (RAAS) is pivotal in the pathophysiology of CVD and renal disease and appears to place individuals at high risk for cardiovascular (CV) and renal events. Results from many large-scale, long-term clinical trials have demonstrated that RAAS blockade with an angiotensin-converting-enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) can significantly decrease CV and renal morbidity and mortality in a wide range of patients. Some of the clinical benefits derived from use of these agents appears to be independent of their ability to lower blood pressure. The combined use of an ACEI and an ARB for antihypertensive therapy has begun to receive considerable attention. Such an approach may seem counterintuitive, but ACEIs and ARBs have distinct and potentially complementary pharmacologic effects. Results from clinical trials thus far suggest that combination therapy with an ACEI plus an ARB may be a rational choice in patients with chronic activation of the RAAS, including those with heart failure or impaired left ventricular systolic function, diabetes, proteinuria, impaired renal function, recent myocardial infarction, or multiple CV risk factors. Results from ongoing, large-scale, clinical endpoint trials will provide important additional information about the benefits of dual RAAS inhibition in patients at high risk for CV morbidity and mortality.