SEATTLE—Patients with congestive heart failure may have an increased risk of adverse events when taking combination therapy with angiotensin receptor blockers (ARBs) and ACE inhibitors.

With the apparent absence of a survival benefit from the combination, it should not be used as on a routine basis in this patient population, according to the lead investigator Rachid Lakhdar, MD, an internal medicine resident at HenryFordHospital in Detroit.

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Adding an ARB to an ACE inhibitor in heart failure patients has been controversial because a previous meta-analysis showed that the combination therapy reduced hospitalizations but did not provide any survival benefit, Dr. Lakhdar said. So, he and his colleagues conducted a literature search for randomized controlled trials comparing ACE inhibitors alone with ACE inhibitor/ARB combination therapy in heart failure patients. Nine trials met the inclusion criteria. The trials included 9,199 patients who received combination therapy and 8,961 who received only an ACE inhibitor.

Dr. Lakhdar, who presented the study findings here at the 10th Annual Scientific Meeting of the Heart Failure Society of America, said the review showed that, compared with ACE inhibitor monotherapy, combination therapy was associated with a 27% increased risk of any adverse events and, specifically, about double the risk of hypotension and worsening of renal function.

“This information should be of interest to nephrologists because they obviously see these heart failure patients, who have an increased problem with renal failure,” Dr. Lakhdar told Renal & Urology News. “This is something we have suspected all along, but now we have put in numbers and have a better idea of the incidence rates.”

In the analysis, trials with longer treatment showed more unfavorable pooled effects with combination therapy than the trials with shorter treatment periods. Therefore, it is possible that some adverse effects of combination therapy not detected in early stages could emerge overtime, Dr. Lakhdar said.

“There is good evidence that the dual blockade of the renin-angiotensin system with the use of an ACE inhibitor and ARB decrease proteinuria, especially in diabetic nephropathy, but when it comes to patients with heart failure the risk may outweigh the benefit,” Dr. Lakhdar observed.