Archief Roodbont

Angiotensin-converting–enzyme inhibitors and angiotensin-receptor blockers (ARBs) are effective treatments for heart failure (HF). However, persistently high rates of adverse outcomes despite treatment have generated interest in combining these drugs. Some study results suggest that such combination therapy reduces the risk for HF hospitalization despite no demonstrable evidence of reduced mortality. However, the safety of this approach is not well characterized.

Investigators analyzed randomized trials comparing combination therapy (an ACE inhibitor plus an ARB) with ACE inhibitor alone in patients with symptomatic left ventricular systolic dysfunction, either accompanying chronic HF or after acute MI. In the four studies with at least 500 subjects and at least 3 months of follow-up (17,337 patients, total), combination therapy was associated with significantly higher rates of adverse-event–related treatment discontinuation (11.5% vs. 9.0%), symptomatic hypotension (11.1% vs. 7.5%), and worsening renal function (4.1% vs. 2.4%) than ACE-inhibitor therapy. Hyperkalemia rates were also higher with combination therapy than with ACE inhibitor alone (1.6% vs. 0.8), but the difference was significant only in patients with chronic HF. The risks for worsening renal function and hyperkalemia with combination therapy were particularly high among patients with chronic systolic HF.

Comment: This study raises substantial concerns about the safety of combination ACE-inhibitor plus angiotensin-receptor blocker therapy in patients with symptomatic LV systolic dysfunction. In practice, combination therapy — if it is used at all — should be reserved for patients who are at relatively low risk for adverse consequences (e.g., those without borderline-high blood pressure or high potassium levels), and such patients should be followed carefully for hypotension, worsening renal function, and hyperkalemia.

— John A. Marx, MD, FAAEM, FACEP

Published in Journal Watch General Medicine November 13, 2007