Angiotensin II Receptor Blockers in the Treatment of Heart Failure

Ross C. Peterson, MD, Mark E. Dunlap, MD


CHF. 2002;8(5) 

In This Article

Abstract and Introduction

Heart failure treatment centers on antagonism of the renin-angiotensin-aldosterone system and adrenergic nervous system. Angiotensin-converting enzyme (ACE) inhibitors have been shown to benefit patients with left ventricular systolic dysfunction irrespective of symptoms. Despite ACE inhibitor use, left ventricular dysfunction continues to progress in most patients. In addition, ACE inhibitors are substantially underused in patients who would benefit, in large part due to physician concern over potential adverse effects. Angiotensin receptor blockers (ARBs) have been proposed as either potential substitutes for ACE inhibitors or as additive therapy for heart failure patients. The authors will review the importance of the renin-angiotensin-aldosterone system in the progression of heart failure, as well as the mechanisms by which ACE inhibitors and ARBs counteract this effect. The clinical evidence to date supporting the use of ARBs in heart failure also will be reviewed. Based on current trials, ARBs are suitable substitutes for ACE inhibitors in patients who have true ACE inhibitor intolerance, but ACE inhibitors should still be considered first-line therapy in the treatment of left ventricular systolic dysfunction and heart failure. ARBs are a reasonable additive therapy in patients on maximal ACE inhibitor therapy who remain symptomatic, especially in patients unable to tolerate blockade.

Activation of the renin-angiotensin-aldosterone system (RAAS) contributes importantly to the pathogenesis of heart failure. Laboratory findings of elevated angiotensin II in heart failure have been supported by clinical evidence of improvements in symptoms and mortality in heart failure patients taking agents that antagonize this system. Angiotensin-converting enzyme (ACE) inhibitors, the most commonly used RAAS antagonists, have been shown to improve the prognosis of patients with left ventricular dysfunction and chronic heart failure.[1,2,3,4,5,6] Despite this benefit, left ventricular dysfunction continues to progress in most patients with heart failure. Evidence suggests important production of angiotensin II by non-ACE pathways both systemically and at the tissue level in the heart and vasculature.[7,8] Angiotensin II subtype I receptor blockers (ARBs) act more distally in the RAAS and might provide more complete blockade than ACE inhibitors. In addition, a significant proportion of patients are intolerant of ACE inhibitor therapy. To determine if ARBs have a role in the treatment of heart failure, we will discuss the rationale for their use and their effects on the RAAS, and evaluate the clinical data supporting the use of ARBs in the treatment of heart failure.