The renin-angiotensin system (RAS) plays a fundamental role in cardiovascular pathophysiology. In particular, angiotensin II (AII) has been identified as a culprit in endothelial and vascular damage, elevated blood pressure, and cardiac failure. Pharmacological inhibition of this system is available through two mechanisms; the reduction of AII formation by inhibition of angiotensin-converting enzyme (ACE), and by direct blockade of the type 1 angiotensin II receptor by angiotensin II receptor blockers (ARBs).
Angiotensin-converting enzyme (ACE) inhibitors have a proven role in the management of elevated blood pressure and diabetes and may confer specific vascular benefit. In patients with chronic heart failure (CHF) secondary to left ventricular systolic dysfunction (LVSD), there is extensive evidence that, when compared to placebo, ACE inhibitors reduce morbidity and mortality. Randomised placebo controlled trials have also shown ACE inhibitors reduce all-cause mortality and major cardiovascular events after myocardial infarction.
Given the unequivocal benefit of ACE inhibitors, initial studies with ARBs in patients with LV dysfunction (in CHF and following myocardial infarction) have focused on two areas: the role of ARBs when compared with ACE inhibitors, and when combined with ACE inhibitors.
Only recently, with the results of the CHARM study, have the role of ARBs when compared to placebo in a population with CHF been clarified. This study also addressed the benefit of ARBs in patients with heart failure and preserved LV systolic function.
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