New Developments in the Management of Chronic Heart Failure

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US Cardiology 2006;2005:2(1):1-5

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Chronic heart failure is common, disabling and deadly. It affects approximately five million people in the US and accounts for over one million hospitalizations annually.1 Despite continued improvements in heart failure therapy, mortality over five years is approximately 50%.2 This article summarizes significant recent developments in pharmacologic and device therapy for heart failure.

Angiotensin Receptor Blockers in the Context of Other Medical Therapies

Angiotensin-converting enzyme (ACE) inhibitors are the standard of care for patients with chronic heart failure due to ventricular systolic dysfunction, based on a large body of clinical trial evidence.3 Angiotensin receptor blockers (ARBs) offer an alternative method of blocking the effects of angiotensin II and have several theoretical advantages over ACE inhibitors. Whereas ACE inhibitors decrease the effects of angiotensin II by (incompletely) blocking its production, ARBs antagonize the angiotensin II receptor directly, theoretically providing a more complete blockade of angiotensin II effects. ARBs may also be better tolerated than ACE inhibitors, with lower incidence of troublesome side effects such as chronic cough. Several recent landmark trials have evaluated the efficacy of ARBs in patients with heart failure, either alone or in combination with ACE inhibitors.

The Valsartan in Heart Failure Trial (VAL-HeFT) evaluated the addition of the ARB valsartan 160mg twice a day to standard therapy (including ACE inhibitors in >90% of patients) in 5,010 patients with New York Heart Association (NYHA) class II-IV heart failure.4 While there was no reduction of all-cause mortality, valsartan did reduce the co-primary end-point of mortality and cardiovascular morbidity by 13% (p=0.009). Subgroup analysis of VAL-HeFT raised the possibility of an adverse effect when valsartan was combined with beta-blockers and ACE inhibitors, although this finding has not been confirmed by subsequent studies and seems likely to be due to chance alone.5

The Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity (CHARM) program evaluated the role of the ARB candesartan in a variety of populations with chronic heart failure. The CHARM program was made up of three constituent trials evaluating candesartan in patients intolerant of ACE inhibitors (CHARM-alternative), patients who were already taking ACE inhibitors (CHARM-added), and with heart failure in the setting of preserved systolic function (CHARM-preserved).

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