Abstract
Clinical trials have proved that blockade of the renin-angiotensin-aldosterone system (RAAS) offers primary and secondary protection of the cardiovascular system, brain, and kidneys. Drugs that interrupt the RAAS do so by several diverse mechanisms but it remains to be fully proved whether these mechanistic differences are associated with meaningful differences in clinical outcomes. This review summarizes current information about the basic mechanisms of action of three classes of anti-RAAS drugs: angiotensin-converting enzyme (ACE) inhibitors, combined ACE-neutral endopeptidase inhibitors, and angiotensin receptor antagonists as well as results of major clinical outcome trials with these agents. Basic and clinical science information is then blended with insights from the clinical pharmacology of anti-RAAS drugs to address four current controversies in clinical medicine: whether ACE inhibitors and angiotensin receptor antagonists are interchangeable, optimal dosing of available agents, potential justification of ACE inhibitor/angiotensin receptor antagonist combinations, and first-line use of anti-RAAS drugs in antihypertensive therapy.