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Abstract

Heart failure (HF), defined as the inability of the heart to pump enough blood to meet tissue oxygen demand, remains a major public health problem in the United States. It affects nearly 5 million Americans, with an incidence of 550,000 new cases per year. The prevalence of HF is projected to increase by 2- to 3-fold by the year 2010 as the population ages and as patients with coronary heart disease survive longer.

Heart failure is a complex disorder that develops through left ventricular (LV) remodeling and progressive LV dysfunction. Chronic activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system contributes to the structural changes in the heart that mediate progressive LV remodeling.

Angiotensin-converting enzyme (ACE) inhibitors and β-blockers have demonstrated, in several large-scale clinical trials, to significantly reduce morbidity and mortality in patients with HF and a reduced LV ejection fraction (LVEF). These agents, along with diuretics for fluid management, are therefore recommended for the treatment of all patients with chronic HF due to systolic dysfunction, as tolerated. The aldosterone inhibitor spironolactone also has been shown to reduce morbidity and mortality in patients with severe HF (New York Heart Association Class IV within 6 months before enrollment). Morbidity and mortality remain high, however, despite these effective therapies.

Angiotensin II receptor blockers (ARBs) are better tolerated than ACE inhibitors and provide specific and complete blockade of the RAAS at the level of the angiotensin II receptor. An important role for ARBs in the management of patients with symptomatic HF and reduced systolic function has been delineated based on several recently completed, large-scale, morbidity and mortality trials. In Val-HeFT (Valsartan Heart Failure Trial), valsartan reduced the composite of death and hospitalization for HF when added to standard HF therapy, although no effect on mortality was observed. In the CHARM (Candesartan in Heart Failure–Assessment of Reduction in Mortality and Morbidity) Program, candesartan demonstrated mortality and morbidity reductions across a broad population of patients with symptomatic HF. Treatment with candesartan reduced cardiovascular death and HF hospitalization not only in patients with prior ACE inhibitor intolerance (CHARM-Alternative), but also in patients receiving optimal medical treatment with ACE inhibitors and β-blockers (CHARM-Added). In a prespecified combined analysis of these 2 CHARM trials, candesartan significantly reduced all-cause mortality. Thus, ACE inhibitors, β-blockers, ARBs, and spironolactone (in patients with severe HF), used at doses proven effective in large-scale clinical trials, comprise the new standard of medical care for patients with chronic HF due to systolic dysfunction.

Am J Hypertens (2004) 17, 249A–249A; doi: 10.1016/j.amjhyper.2004.03.663

Heart failure, systolic dysfunction, angiotensin II receptor antagonists
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© American Journal of Hypertension, Ltd. 2004
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