Use of angiotensin II receptor blocker in heart failure with reduced ejection fraction
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
Blockade of the renin-angiotensin-aldosterone system (RAAS) is a key component of treatment of patients with heart failure (HF) with reduced ejection fraction (HFrEF, also known as systolic HF or HF due to systolic dysfunction) [1-3]. (See "Overview of the therapy of heart failure with reduced ejection fraction".)
This topic will discuss the clinical evidence on and use of ARB therapy in HFrEF. The role of angiotensin receptor-neprilysin inhibitor therapy in HFrEF, an overview of pharmacologic treatment of HFrEF, and mechanisms of action of ARB therapy are discussed separately. (See "Use of angiotensin receptor-neprilysin inhibitor in heart failure with reduced ejection fraction" and "Pharmacologic therapy of heart failure with reduced ejection fraction" and "Angiotensin converting enzyme inhibitors and receptor blockers in heart failure: Mechanisms of action".)
ANGIOTENSIN II RECEPTOR BLOCKER
Mechanism of action — Angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors reduce the stimulation of angiotensin II (AT) receptors via different mechanisms (figure 1). Given the difference in mechanisms, it was previously postulated that ARB therapy would provide an advantage over ACE inhibitor therapy but the evidence has shown that ARB therapy is not superior to ACE inhibitor therapy for heart failure (HF).
ACE inhibitors block the formation of angiotensin II, thereby decreasing the amount of angiotensin available to both AT type 1 (AT1) and AT type 2 (AT2) receptors. ARBs selectively block the binding of angiotensin II to the AT1 receptor, but do not affect the AT2 receptor . The clinical importance of this is uncertain, since the AT1 receptor seems to dominate. (See "Actions of angiotensin II on the heart" and "Differences between angiotensin-converting enzyme inhibitors and receptor blockers".)
Another difference is that ACE inhibitors, but not ARBs, reduce kinin degradation, since ACE is also a kininase (figure 1). The accumulation of kinins may mediate some of the benefits as well as the adverse effects of ACE inhibitors. One important clinical consequence resulting from the lack of kinin accumulation is that the ARBs do not induce cough, a complication that occurs in 3 to 20 percent of patients treated with ACE inhibitors. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- ANGIOTENSIN II RECEPTOR BLOCKER
- Mechanism of action
- Indications for use of angiotensin II receptor blocker
- Evidence on angiotensin II receptor blocker
- - Intolerant of ACE inhibitor
- - Compared with ACE inhibitor
- - Use MRA rather than ARB with ACE inhibitor
- Addition of MRA to ACE inhibitor improves survival
- Addition of ARB to ACE inhibitor does not improve survival
- - Avoid combination of ARB with ACE inhibitor and MRA
- Adverse effects
- Agent and dose
- SUMMARY AND RECOMMENDATIONS