Clinical research studyAngiotensin-Converting Enzyme Inhibitor Associated Cough: Deceptive Information from the Physicians' Desk Reference
Section snippets
Search Strategy and Selection of Studies
We conducted PUBMED/EMBASE/CENTRAL searches from 1990 to February 2010 for studies using the terms: ‘angiotensin-converting enzyme inhibitors’ and by using the names of individual ACE inhibitors (Enalapril, lisinopril, perindopril, moexipril, ramipril, trandalopril, and fosinopril). We limited our search to studies in humans from 1990 to February 2010. We checked the reference lists of review articles, meta-analyses, and original studies identified by the electronic search to find other
Study Selection
We identified 2811 RCTs through electronic and hand searches, of which 125 trials (159 comparison arms) fulfilled the inclusion criteria and were chosen for this analysis (Figure 1). We excluded trials that involved a combination of ACE inhibitors and angiotensin receptor blockers (ARBs; example: ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint [ONTARGET] Trial), and studies that only enrolled patients with known intolerance to ACE inhibitors. However, studies using a
Discussion
The results of the present analysis of nearly 200,000 patients suggests that the rate of a common nuisance adverse effect with ACE inhibitors, cough, is grossly under-reported in the PDR/drug label and is several folds greater in the literature.
Conclusions
In this largest meta-analysis to date involving nearly 200,000 patients, the incidence of ACE inhibitor-associated cough and the withdrawal rate (the more objective metric) due to cough is several-fold greater in the literature than reported in the PDR (and the drug label) and is likely greater in the real-world compared to data from RCTs presented here. Action must be taken to ensure that the drug labeling is regularly updated both for safety and for medication-specific adverse effects.
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Funding: This study was supported by a grant from Boehringer Ingelheim.
Conflict of Interest: Drs. Bangalore and Kumar do not have any potential conflicts of interest to disclose. Dr. Messerli is on the speaker's bureau or ad hoc consulting for Pfizer, Abbott, Takeda, Nicox, Boehringer Ingelheim, Merck, Novartis, and Daiichi-Sankyo.
Authorship: All authors have read and approved the manuscript. All authors met the criteria for authorship, had access to data, and played an important role in writing the manuscript. All activities and decisions involved in the meta-analysis and preparation of the manuscript were performed completely independently with no input or review by Boehringer Ingelheim.