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Original Research: COPD |

Cardiovascular Safety in Patients Receiving Roflumilast for the Treatment of COPDCardiovascular Safety of Roflumilast

William B. White, MD; Glen E. Cooke, MD; Peter R. Kowey, MD; Peter M. A. Calverley, MD; Dirk Bredenbröker, MD; Udo-Michael Goehring, MD; Haiyuan Zhu, PhD; Hassan Lakkis, PhD; Hans Mosberg, MD; Paul Rowe, MD; Klaus F. Rabe, MD, PhD
Author and Funding Information

From the Calhoun Cardiology Center (Dr White), University of Connecticut School of Medicine, Farmington, CT; Ross Heart Hospital (Dr Cooke), College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH; Division of Cardiology (Dr Kowey), Lankenau Medical Center, and Jefferson Medical College, Philadelphia, PA; University Hospital Aintree (Dr Calverley), Liverpool, England; Respiratory Medicine (Drs Bredenbröker, Goehring, and Mosberg), Nycomed: a Takeda Company, Zurich, Switzerland; Forest Research Institute Inc (Drs Zhu, Lakkis, and Rowe), Jersey City, NJ; and University Kiel and Lung Clinic Grosshansdorf, members of the German Center for Lung Research (Dr Rabe), Grosshansdorf, Germany.

Correspondence to: William B. White, MD, Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut School of Medicine, 263 Farmington Ave, Farmington, CT 06030-3940; e-mail: wwhite@nso1.uchc.edu


For editorial comment see page 723

Funding/Support: Funding was provided by Research and Development, Forest Research Institute Inc, a wholly owned subsidiary of Forest Laboratories, Inc, Jersey City, NJ, and Nycomed: a Takeda Company, Zurich, Switzerland.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(3):758-765. doi:10.1378/chest.12-2332
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Background:  Evaluation of cardiovascular safety for new therapies for COPD is important because of a high prevalence of cardiac comorbidities in the COPD population. Hence, we evaluated the effects of roflumilast, a novel oral phosphodiesterase 4 inhibitor developed for the treatment and prevention of COPD exacerbations, on major adverse cardiovascular events (MACEs).

Methods:  Intermediate- and long-term placebo-controlled clinical trials of roflumilast in COPD were pooled and assessed for potential cardiovascular events. Studies comprised 14 12- to 52-week placebo-controlled trials in patients with moderate to very severe COPD. All deaths and serious nonfatal cardiovascular events were evaluated by an independent adjudication committee blinded to study and treatment. The MACE composite of cardiovascular death, nonfatal myocardial infarction, and stroke was analyzed according to treatment group.

Results:  Of 6,563 patients receiving roflumilast, 52 experienced MACEs (14.3 per 1,000 patient-years), and of 5,491 patients receiving placebo, 76 experienced MACEs (22.3 per 1,000 patient-years). The MACE composite rate was significantly lower for roflumilast compared with placebo (hazard ratio, 0.65; 95% CI, 0.45-0.93; P = .019).

Conclusions:  A lower rate of cardiovascular events was observed with roflumilast than with placebo in patients with COPD, indicating the lack of a cardiovascular safety signal when treating patients with COPD. Potential cardiovascular benefits of roflumilast should be evaluated in future controlled clinical trials.

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