Cardiovascular safety of roflumilast.

In this issue of CHEST (see page 758), White et al 1 report signifi cantly lower major adverse cardiovascular events (MACEs) for rofl umilast compared with placebo (hazard ratio, 0.65; 95% CI, 0.45-0.93; P 5 .019) from data in 12,054 patients with COPD. In addition to the studies analyzed not being designed or powered to examine cardiovascular outcomes, we would like to point out other limitations of the study. First, the incidence of nonfatal stroke was the only component of MACEs that showed a statistically signifi cant difference. It may not be appropriate to use a composite outcome if the magnitude of treatment effects is not comparable across the outcome components. 2 It may be fair to say that rofl umilast could decrease cerebrovascular events but not cardiovascular events or mortality because rofl umilast was not associated with a lower incidence of such MACE components compared with placebo. Second, the incidence of atrial fi brillation was not included in the study. Our recent meta-analysis showed that atrial fi brillation was signifi cantly more frequent with rofl umilast than with placebo (0.4% vs 0.2%; P 5 .02). 3 The COPD safety pool White et al 1 used included this information, and they should have incorporated it into the study. Third, the discontinuation rate because of adverse effects was signifi cantly more frequent with rofl umilast than with placebo (15% vs 9.2%, P , .0001). 3 The imbalance of dropout rates between the two groups may have affected the study results. The results may have been quite different if all patients recruited for rofl umilast continued to take the drug during the entire study period. Financial/nonfi nancial disclosures: The authors have reported to CHEST the following confl icts: Dr MacNee has acted in an advisory capacity for GlaxoSmithKline plc; Pfi zer, Inc; Novartis AG; and Almirall, SA. He has received payment from GlaxoSmithKline plc and Pfi zer, Inc for research programs and clinical activities and has also received payments from Boehringer-Ingelheim GmbH, GlaxoSmithKline, AstraZeneca, Novartis AG, and Janssen Pharmaceuticals to travel to meetings and/or present at conferences. Dr Maclay has reported no potential confl icts of interest exist with any companies/organi zations whose products or services may be dis cussed in this article . Correspondence to: John D. Maclay, MBChB MD, University of Edinburgh, Centre for Infl ammation Research, 47 Little France Crescent, Edinburgh EH16 4SB, Scotland; e-mail: johnmaclay@ gmail.com © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1352