title: Inhaled beta-2-agonists/muscarinic antagonists and acute myocardial infarction in COPD patients.
abstract: OBJECTIVE
  Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with beta-2-agonists (B2A) and muscarinic antagonists (MA). A systematic review (including a meta-analysis for drug classes with sufficient sample size) was conducted assessing the association between B2A or MA and acute myocardial infarctions (MI) in COPD patients.
  
  
  METHODS
  Comprehensive literature search in electronic databases (MEDLINE, Cochrane database) was performed (January 1, 1946-April 1, 2013). Results were presented by narrative synthesis including a comprehensive quality assessment. In the meta-analysis, a random effects model was used for estimating relative risk estimates for acute MI.
  
  
  RESULTS
  Eight studies (two systematic reviews, two randomized controlled trials, and four observational studies) were comprised. Most studies comparing tiotropium vs. placebo showed a decreased MI risk for tiotropium, whereas for studies with active control arms no clear tendency was revealed. For short-acting B2A, an increased MI risk was shown after first treatment initiation. For all studies, a good quality was found despite some shortcomings in ADE-specific criteria. A meta-analysis could be conducted for tiotropium vs. placebo only, showing a relative risk reduction of MI (0.74 [0.61-0.90]) with no evidence of statistical heterogeneity among the included trials (I(2) = 0%; p = 0.8090).
  
  
  CONCLUSIONS
  An MI-protective effect of tiotropium compared to placebo was found, which might be attributable to an effective COPD treatment leading to a decrease in COPD-related cardiovascular events. Further studies with effective control arms and minimal CV risk are required determining precisely tiotropium's cardiovascular risk.
authors.affiliation: Institute for Medical Information Sciences, Biometry, and Epidemiology, Ludwig-Maximilians Universitaet Muenchen, Marchioninistr. 15, D-81377 Munich, Germany. Electronic address: rottenk@ibe.med.uni-muenchen.de.
authors.forename: Marietta
authors.initials: M
authors.lastname: Rottenkolber
authors.affiliation: Institute of Health Economics and Management and Munich Center of Health Sciences, Ludwig-Maximilians-Universitaet Muenchen, Ludwigstr. 28, D-80539 Munich, Germany; Institute of Health Economics and Management, HelmholtzZentrum München - German Research Centre for Environmental Health, Member of the German Center for Lung Research, Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rottenkolber
authors.affiliation: Medizinische Klinik und Poliklinik V, University Hospital, Ludwig-Maximilians-Universitaet, Ziemssenstr. 1, D-80336 München, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Fundació Institut Català de Farmacologia Servei de Farmacologia, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 119-129, E-08029 Barcelona, Spain; Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Edifici M, 08193 Bellaterra, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ibáñez
authors.affiliation: Novartis Farmaceutica S.A., Apartado 708, E-08080 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Fortuny
authors.affiliation: Fundació Institut Català de Farmacologia Servei de Farmacologia, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 119-129, E-08029 Barcelona, Spain; Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Edifici M, 08193 Bellaterra, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ballarin
authors.affiliation: Fundació Institut Català de Farmacologia Servei de Farmacologia, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 119-129, E-08029 Barcelona, Spain; Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Edifici M, 08193 Bellaterra, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Sabaté
authors.affiliation: Fundació Institut Català de Farmacologia Servei de Farmacologia, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 119-129, E-08029 Barcelona, Spain.
authors.forename: Pili
authors.initials: P
authors.lastname: Ferrer
authors.affiliation: Philipp Klee-Institute for Clinical Pharmacology, HELIOS Clinic Wuppertal, Heusnerstr. 40, D-42283 Wuppertal, Germany; Department of Clinical Pharmacology, School of Medicine, Faculty of Health, Witten/Herdecke University, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Thürmann
authors.affiliation: Institute for Medical Information Sciences, Biometry, and Epidemiology, Ludwig-Maximilians Universitaet Muenchen, Marchioninistr. 15, D-81377 Munich, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Hasford
authors.affiliation: Philipp Klee-Institute for Clinical Pharmacology, HELIOS Clinic Wuppertal, Heusnerstr. 40, D-42283 Wuppertal, Germany; Department of Clinical Pharmacology, School of Medicine, Faculty of Health, Witten/Herdecke University, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Schmiedl
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D004812:Epidemiologic Methods; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D009203:Myocardial Infarction / Q000139:chemically induced*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects; D000069447:Tiotropium Bromide
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
keywords: Acute myocardial infarction; Beta-2-agonists; Chronic obstructive pulmonary disease; Muscarinic antagonists; Systematic review