title: Cardiovascular safety in patients receiving roflumilast for the treatment of COPD.
abstract: 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.
authors: Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT. Electronic address: wwhite@nso1.uchc.edu.
authors: William B
authors: WB
authors: White
authors: Ross Heart Hospital, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH.
authors: Glen E
authors: GE
authors: Cooke
authors: Division of Cardiology, Lankenau Medical Center, and Jefferson Medical College, Philadelphia, PA.
authors: Peter R
authors: PR
authors: Kowey
authors: University Hospital Aintree, Liverpool, England.
authors: Peter M A
authors: PMA
authors: Calverley
authors: Respiratory Medicine, Nycomed: a Takeda Company, Zurich, Switzerland.
authors: Dirk
authors: D
authors: Bredenbröker
authors: Respiratory Medicine, Nycomed: a Takeda Company, Zurich, Switzerland.
authors: Udo-Michael
authors: UM
authors: Goehring
authors: Forest Research Institute Inc, Jersey City, NJ.
authors: Haiyuan
authors: H
authors: Zhu
authors: Forest Research Institute Inc, Jersey City, NJ.
authors: Hassan
authors: H
authors: Lakkis
authors: Respiratory Medicine, Nycomed: a Takeda Company, Zurich, Switzerland.
authors: Hans
authors: H
authors: Mosberg
authors: Forest Research Institute Inc, Jersey City, NJ.
authors: Paul
authors: P
authors: Rowe
authors: University Kiel and Lung Clinic Grosshansdorf, members of the German Center for Lung Research, Grosshansdorf, Germany.
authors: Klaus F
authors: KF
authors: Rabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000631:Aminopyridines / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology / Q000517:prevention & control; D003521:Cyclopropanes / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors; D015995:Prevalence; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast