Cardiac protection: Evolving role of angiotensin receptor blockers

Congestive heart failure (HF) is a common and serious public health problem affecting approximately 5 million Americans. Recent treatment strategies have focused on attenuating the effects of angiotensin (Ang) II, which include vasoconstriction, sodium retention, sympathetic activation, and cell growth. Angiotensin-converting enzyme (ACE) inhibitors, which primarily block the systemic formation of Ang II, reduce HF-related morbidity and mortality rates. However, ACE inhibitors may not suppress Ang II activity over their entire dosing interval and, with long-term therapy, Ang II levels tend to return to normal. It is now known that Ang II can be formed independent of ACE by the act on of enzymes such as chymase in local tissues, including the heart. Despite the established benefits of ACE inhibitor treatment, HF-related morbidity and mortality rates continue to increase because the aging of the population is placing more patients at risk of HF. By acting at the receptor level, Ang II receptor blockers (ARBs) should, at least theoretically, provide more 'complete' Ang II blockade. Early evidence suggests that ARBs induce hemodynamic improvement in patients with HF and may reduce mortality rates. Because ACE inhibitors and ARBs block Ang II through fundamentally different mechanisms, the combination may provide additive therapeutic effects in patients with HF. Results from a pilot study suggest that the combination of an ACE-inhibitor and valsartan results in a more thorough inhibition of Ang II and an additive improvement in cardiac hemodynamics. Clinical trials now in progress will elucidate the effects of combined ACE inhibitor and ARB therapy on HF-related morbidity and mortality rates.