Beyond blood pressure: evidence for cardiovascular, cerebrovascular, and renal protective effects of renin–angiotensin system blockers

For patients with hypertension, effective control of blood pressure (BP) reduces cardiovascular (CV), and renal risk. Antihypertensive agents that offer benefits that extend beyond those associated with BP reduction alone, to include tissue protective effects and effects on the vasculature, may be of benefit for many patients with increased CV risk due to comorbidities or prior history of CV events. Renin–angiotensin system (RAS) blockers [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)] are guideline-recognized, highly effective antihypertensive agents that exert their BP-lowering action through different mechanisms at different levels of the RAS. Large-scale clinical studies suggest that small, between-treatment differences in BP lowering do not account for observed outcome differences between RAS blockers and other antihypertensive agents. Analysis of data from seminal clinical studies and meta-analyses identify that, controlling for effects on BP control, RAS blockers may be more effective than calcium channel blockers (CCBs) in reducing risk of myocardial infarction and congestive heart failure; ARBs may be more effective than either ACEIs or β blockers in stroke prevention; CCBs may be more effective than RAS blockers in stroke prevention; and ARBs may be more effective than β blockers in reducing left ventricular hypertrophy. This review considers the rationale and evidence for benefits of RAS blockade beyond BP lowering, and highlights the differences between ARBs and ACEIs, and between agents within these drug classes.