NEW ORLEANS — Angiotensin receptor blockers were associated with significantly greater risk of worsening renal function than were angiotentin-converting enzyme inhibitors in patients with systolic heart failure in a meta-analysis of all seven head-to-head comparative randomized, controlled, clinical trials, Dr. Rachid Lakhdar reported at the annual meeting of the American College of Cardiology.
“The ARBs are trying to make it as first-line drugs. The most recent guidelines put them as a class IIa indication, allowing them as first-line therapy in patients with mild to moderate heart failure and reduced left ventricular function,” he said in an interview.
“Our conclusion from the meta-analysis is maybe that's not such a good idea, and ARBs should continue to be second line, to be used when ACE inhibitors are contraindicated,” he continued.
The meta-analysis involved 20,143 systolic dysfunction heart failure patients who were randomized to an ACE inhibitor or ARB. Among the studies they were drawn from were the Valsartan in Acute Myocardial Infarction Trial (VALIANT), the first and second Evaluation of Losartan in the Elderly (ELITE I and II), the Optimal Therapy in Myocardial Infarction With the Angiotensin II Antagonist Losartan (OPTIMAAL) trial, and the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study.
Carried out without commercial support, the meta-analysis clearly showed that overall side effects were significantly less frequent with ARBs. Indeed, the combined incidence of cough, angioedema, hyperkalemia, hypotension, and worsening renal function was 42% less with ARB therapy than with ACE inhibitor therapy in patients with systolic heart failure. However, the relative risk of worsening renal function was 60% greater with angiotensin receptor blockers, according to Dr. Lakhdar, a third-year resident at the Henry Ford Hospital System, Detroit.
The ARB and ACE inhibitor arms were evenly matched in terms of diuretic therapy and other potential confounders.
“This is a new observation that certainly needs more research, including a prospective study to pinpoint the pathophysiology as to why ARBs are more likely to worsen renal function,” the physician added.
Discussant Dr. Lynne E. Wagoner predicted that guideline-writing committees are going to have to pay attention to the new meta-analysis.
“Cough is the major reason ACE inhibitors are discontinued. Often that cough is not severe and certainly is not life threatening,” said Dr. Wagoner, medical director of the cardiac transplantation division at the University of Cincinnati.
“However, the risk of worsening renal function is potentially life threatening and therefore should be stressed in guideline recommendations. ARBs should remain second-line therapy behind ACE inhibitors as a result of these findings,” he continued.