SEATTLE — Adding an angiotensin receptor blocker to ACE inhibitor therapy in patients with heart failure significantly increased the risk of hypotension and renal failure, with a trend toward an increased risk for hyperkalemia, compared with ACE inhibitor therapy alone, in a meta-analysis of randomized, controlled trials, Dr. Rachid Lakhdar reported.
A previous meta-analysis of randomized, controlled studies found that combination therapy with an angiotensin receptor blocker (ARB) and an ACE inhibitor reduced hospitalizations in patients with heart failure but provided no survival benefit, he said in poster presentation at the annual meeting of the Heart Failure Society of America. The earlier meta-analysis did not analyze the safety of this drug combination.
Dr. Lakhdar and his coinvestigator, Dr. Mouaz H. Al-Mallah, both of Henry Ford Hospital, Detroit, searched the medical literature and abstracts from medical meetings and analyzed safety data from nine studies including 18,160 patients with heart failure. The incidence of side effects was low but was 25% higher in the combination therapy arms, compared with ACE inhibitor therapy alone, they reported.
Patients on combined therapy were 54% more likely to develop hypotension and twice as likely to develop worsened renal function, compared with patients on an ACE inhibitor alone. A 2.5-fold increase in risk for hyperkalemia was not statistically significant.
“Those side effects—hypotension, hyperkalemia, and renal failure—are related directly or indirectly to reduced angiotensin II formation,” the investigators noted. The rates of cough and angioedema did not differ significantly between groups.
Not all the studies showed a significant increase in side effects with the combination therapy, perhaps owing to small sample size, short follow-up, or the characteristics of different drugs and doses. The longer trials found more side effects than shorter trials did, so it may be that some adverse events associated with the combination therapy would have shown up over time, Dr. Lakhdar and Dr. Al-Mallah suggested. “The presence of this excess risk, lack of a definitive survival benefit of this strategy, and the availability of other agents with proven survival benefit in heart failure in combination with ACE inhibitors suggests that the addition of an ARB to ACE inhibitor therapy should be discouraged,” they said.
The investigators reported that they have no associations with the companies that make the drugs.