Beta-blocker use and acute exacerbations of COPD following myocardial infarction: a Danish nationwide cohort study

Introduction Patients with chronic obstructive pulmonary disease (COPD) are undertreated with beta-blockers following myocardial infarction (MI), possibly due to fear for acute exacerbations of COPD (AECOPD). Is beta-blocker use associated with increased risk of AECOPD in patients following first-time MI? Methods Danish nationwide study of patients with COPD following hospitalisation for MI from 2003 to 2015. Multivariable, time-dependent Cox regression accounting for varying beta-blocker use based on claimed prescriptions during up to 13 years of follow-up. Results A total of 10 884 patients with COPD were discharged after first-time MI. The 1-year rate of AECOPD was 35%, and 65% used beta-blockers at 1 year. Beta-blocker use was associated with a lower risk of AECOPD (multivariable-adjusted HR 0.78, 95% CI 0.74–0.83). This association was independent of the type of MI (HR 0.70, 95% CI 0.59–0.83 in ST-elevation MI (STEMI) and HR 0.80, 95% CI 0.75–0.84 in non-STEMI), presence or absence of heart failure (HR 0.82, 95% CI 0.74–0.90 and HR 0.77, 95% CI 0.72–0.82, respectively), beta-blocker dosage and type, as well as exacerbation severity. Results were similar in 1118 patients with full data on COPD severity and symptom burden (median forced expiratory volume in 1 s as percentage of predicted was 46 and majority had moderate dyspnoea), and in 1358 patients with severe COPD and frequent AECOPD with a high 1-year rate of AECOPD of 70%. Discussion Beta-blocker use was not associated with increased risk of AECOPD following MI. This finding was independent of COPD severity, symptom burden and exacerbation history, and supports the safety of beta-blockers in patients with COPD, including high-risk patients with severe disease.

[1]  J. Curtis,et al.  Metoprolol for the Prevention of Acute Exacerbations of COPD. , 2019, The New England journal of medicine.

[2]  M. Jensen,et al.  Beta-blocker, aspirin and statin usage after first-time myocardial infarction in patients with chronic obstructive pulmonary disease: a nationwide analysis from 1995 to 2015 in Denmark. , 2019, European heart journal. Quality of care & clinical outcomes.

[3]  M. Schumacher,et al.  Simulation shows undesirable results for competing risks analysis with time-dependent covariates for clinical outcomes , 2018, BMC Medical Research Methodology.

[4]  F. Martinez,et al.  &bgr;‐Blocker Therapy and Clinical Outcomes in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk. An Observational Substudy of SUMMIT , 2018, Annals of the American Thoracic Society.

[5]  P. Stang,et al.  Methods for time‐varying exposure related problems in pharmacoepidemiology: An overview , 2017, Pharmacoepidemiology and drug safety.

[6]  E. Horváth-Puhó,et al.  Conditioning on future exposure to define study cohorts can induce bias: the case of low-dose acetylsalicylic acid and risk of major bleeding , 2017, Clinical epidemiology.

[7]  Chong-Jen Yu,et al.  Impact of selective and nonselective beta-blockers on the risk of severe exacerbations in patients with COPD , 2017, International journal of chronic obstructive pulmonary disease.

[8]  J. Curtis,et al.  Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD) , 2017, Respiratory Research.

[9]  M. R. Siddiqui,et al.  Global Initiative for Chronic Obstructive Lung Disease (GOLD) , 2017 .

[10]  C. Baglole,et al.  Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease , 2017, Respiratory Research.

[11]  Maciej Liskiewicz,et al.  Robust causal inference using Directed Acyclic Graphs: the R package , 2018 .

[12]  R. Wilcox,et al.  β-Blockers, heart disease and COPD: current controversies and uncertainties , 2016, Thorax.

[13]  H. Bøtker,et al.  Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study , 2016, BMJ Open.

[14]  P. Lange,et al.  Danish Register of chronic obstructive pulmonary disease , 2016, Clinical epidemiology.

[15]  J. Hallas,et al.  Medically treated exacerbations in COPD by GOLD 1-4: A valid, robust, and seemingly low-biased definition. , 2015, Respiratory medicine.

[16]  Sigrun Alba Johannesdottir Schmidt,et al.  The Danish National Patient Registry: a review of content, data quality, and research potential , 2015, Clinical epidemiology.

[17]  W. Bailey,et al.  β-Blockers are associated with a reduction in COPD exacerbations , 2015, Thorax.

[18]  Danielle M. Enserro,et al.  Implications of the US Cholesterol Guidelines on Eligibility for Statin Therapy in the Community: Comparison of Observed and Predicted Risks in the Framingham Heart Study Offspring Cohort , 2015, Journal of the American Heart Association.

[19]  J. Smith,et al.  β‐Blocker Use and Mortality in COPD Patients After Myocardial Infarction: A Swedish Nationwide Observational Study , 2015, Journal of the American Heart Association.

[20]  Adam Hawkins,et al.  Risk factors for acute exacerbations of COPD in a primary care population: a retrospective observational cohort study , 2014, BMJ Open.

[21]  P. Andersen,et al.  Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. , 2014, Annals of internal medicine.

[22]  Henrik Toft Sørensen,et al.  The Danish Civil Registration System as a tool in epidemiology , 2014, European Journal of Epidemiology.

[23]  G. Melina,et al.  β-Blockers improve survival of patients with chronic obstructive pulmonary disease after coronary artery bypass grafting. , 2013, The Annals of thoracic surgery.

[24]  D. Atar,et al.  ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation , 2013 .

[25]  J. Barberà,et al.  Echocardiographic abnormalities in patients with COPD at their first hospital admission , 2012, European Respiratory Journal.

[26]  P. Lindenauer,et al.  Association between β-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension , 2012, Thorax.

[27]  S. Suissa,et al.  Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality , 2012, Thorax.

[28]  Jeroen J. Bax,et al.  ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation , 2012 .

[29]  J. Marrugat,et al.  Long-term prognosis of first myocardial infarction according to the electrocardiographic pattern (ST elevation myocardial infarction, non-ST elevation myocardial infarction and non-classified myocardial infarction) and revascularization procedures. , 2011, The American journal of cardiology.

[30]  P. Lange,et al.  Validity and underrecording of diagnosis of COPD in the Danish National Patient Registry. , 2011, Respiratory medicine.

[31]  Brian J Lipworth,et al.  Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study , 2011, BMJ : British Medical Journal.

[32]  M. Alan Brookhart,et al.  Healthy User and Related Biases in Observational Studies of Preventive Interventions: A Primer for Physicians , 2011, Journal of General Internal Medicine.

[33]  J. Wedzicha,et al.  Susceptibility to exacerbation in chronic obstructive pulmonary disease. , 2010, The New England journal of medicine.

[34]  F. Rutten,et al.  Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. , 2010, Archives of internal medicine.

[35]  B. J. Knoll,et al.  Changes in β2-adrenoceptor and other signaling proteins produced by chronic administration of ‘β-blockers’ in a murine asthma model , 2008 .

[36]  Hui Peng,et al.  Changes in beta 2-adrenoceptor and other signaling proteins produced by chronic administration of 'beta-blockers' in a murine asthma model. , 2008, Pulmonary pharmacology & therapeutics.

[37]  E. Vicaut,et al.  STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). , 2006, European heart journal.

[38]  L. Køber,et al.  Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. , 2006, European heart journal.

[39]  D. Postma,et al.  Clinical Investigations: COPDDetrimental Effects of β-Blockers in COPD: A Concern for Nonselective β-Blockers , 2005 .

[40]  D. Postma,et al.  Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers. , 2005, Chest.

[41]  J. Curtis,et al.  Beta-blockers as single-agent therapy for hypertension and the risk of mortality among patients with chronic obstructive pulmonary disease. , 2004, The American journal of medicine.

[42]  E. Salpeter,et al.  Cardioselective beta-blockers for chronic obstructive pulmonary disease. , 2005, The Cochrane database of systematic reviews.