Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction

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Abstract
Dual suppression of the renin angiotensin aldosterone system with combination therapy that includes angiotensin II type I receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors is gaining interest among heart failure (HF) experts.1-13 However, current guidelines for recommended pharmacotherapy in patients with HF have not endorsed this approach.14,15 This strategy could be very important given the continuing high mortality and morbidity among patients with HF. Prior reviews of this strategy suggested that there was no conclusive evidence for a survival advantage from combination ARB plus ACE inhibitor therapy; however, there were significant reductions in HF hospitalizations in subjects with chronic HF.16-19 Recently, an additional large clinical trial investigating the efficacy of combination ARB plus ACE inhibitor therapy vs background treatment that includes ACE inhibitors in subjects with acute myocardial infarction (AMI) and symptomatic left ventricular (LV) dysfunction has been published,20 and the results lend further support for the combination strategy in reducing HF hospitalizations but not overall mortality. Despite the initial enthusiasm for combination ARBs plus ACE inhibitors as a viable therapeutic option for subsets of patients with symptomatic LV dysfunction, concerns about adverse effects including severe or life-threatening hyperkalemia21-31 persist and may limit the application of this strategy.

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