ACE inhibitor-associated cough more common than drug labels report
MedWire News: ACE inhibitor-associated cough and the resultant discontinuations of ACE-inhibitors both occur at much higher rates in clinical trials than indicated on drug labels or in reference guides, results from a large meta-analysis suggest.
The study authors comment that the report of enalapril-associated cough at an incidence of 1.3% in the Physicians' Desk Reference (PDR) is so low it appears "laughable" to practicing physicians.
They highlight that the rates of cough and withdrawal seen in clinical practice are likely to be higher than in clinical trials, so the gap between real-world rates and those given to patients and physicians is probably even greater than their findings suggest.
Franz Messerli (Brigham and Women's Hospital, Boston, Massachusetts, USA) and team analyzed 125 studies involving a total of 198,130 patients randomly allocated to receive ACE inhibitors (n=111,798) or other treatment (n=86,437; placebo or otherwise).
All studies were published between 1990 and 2010, and all patients were followed-up for at least 3 months.
Pooled and weighted findings revealed that cough occurred at a rate of 11.48% among patients taking enalapril - nine times greater than that reported in the PDR (p<0.001).
The withdrawal rate due to enalapril-related cough was 31 times greater than the rate reported in the PDR, at 3.08% versus 0.10% (p<0.001).
As reported in the American Journal of Medicine, similar results were obtained when cough and withdrawal rates associated with other types of ACE inhibitors were assessed.
The researchers also observed a progressive increase in the rates of ACE inhibitor-associated cough reported by randomized controlled trials (RCTs) over the past 20 years. They found, however, that during this time the PDR reported consistently lower rates than those illustrated by RCTs.
In an accompanying editorial, Victor Serebruany (Johns Hopkins University, Baltimore, Maryland, USA) highlighted the need to address discrepancies between the safety profiles of drugs.
He wrote: "The Food & Drug Administration should require collecting registries independent from the drug company's funding, especially when phase III trials reveal some unexpected complication."
Messerli and team also offer this suggestion and say that although it may prove difficult to accurately assess the rates of all nonspecific side effects, "medication-specific adverse effects such as cough and angioedema with ACE inhibitors [and] pedal edema with calcium antagonists… should be systematically collected on an ongoing basis and should be reflected in the label."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Lauretta Ihonor