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?-Blocker Therapy and Risk of Chronic Obstructive Pulmonary Disease - A Danish Nationwide Study of 1·3 Million Individuals.

ABSTRACT: Background:The possible association between ?-adrenoceptor antagonists (?-blockers) and risk of COPD is controversial. The objective of the present study was to test whether ?-blocker use is associated with susceptibility to the disease. Methods:A total of 301,542 new users of ?-blockers and 1,000,633 new users of any other antihypertensive drugs aged 30-90?years without any history of COPD hospitalizations were included in the present study and followed in the Danish National Patient Registry for incident admissions for COPD and COPD death between 1995 and 2015. Multiple adjusted cox regression models were used to examine the association between use of ?-blockers and COPD hospitalization. Additionally, subgroup analyses based on underlying diseases at baseline or duration of treatment were performed. Findings:People treated with ?-blockers continuously for more than 6?months had a lower risk of COPD hospitalization during follow-up compared to people treated with any other antihypertensive drugs (adjusted hazard ratio [HRadjusted] 0·80, 95% CI 0·79-0·82). Risk of COPD hospitalization was lowered in the groups treated with ?-blockers among patients with ischemic heart disease (0·72, 0·69-0·75), cardiac arrhythmias (0·76, 0·72-0·80), asthma (0·69, 0·61-0·79), hypertension (0·91, 0·86-0·96), and diseases of the pulmonary circulation (pulmonary embolism and cor pulmonale) (0·72, 0·59-0·87). All-cause mortality as well as risk of COPD death during follow-up was lower in the group treated with ?-blockers compared to the group treated with any other antihypertensive drugs (0·56, 0·53-0·59). Interpretation:Treatment with ?-blockers seems to reduce risk of COPD hospitalization and mortality compared to treatment with any other antihypertensive drugs. Funding:The Danish Council for Independent Research in Denmark (grant no. 4183-00569B), The Research Foundation of Health Science in Region Zealand (grant no. RSSF2017000661 and no. 15-000342), The Research Foundation of Medical Science (A.P. Møller Foundation, grant no. 16-68), The Research Foundation in memory of King Christian 10th (grant no. 142/2017), Aase & Ejnar Danielsen's Research Foundation (grant no. 10-001946), and Lundbeck Foundation (grant no. R252-2017-1690).

SUBMITTER: Nielsen AO

PROVIDER: S-EPMC6537528 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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β-Blocker Therapy and Risk of Chronic Obstructive Pulmonary Disease - A Danish Nationwide Study of 1·3 Million Individuals.

Nielsen Anne Orholm AO Pedersen Lars L Sode Birgitte Fischer BF Dahl Morten M

EClinicalMedicine 20190129

<h4>Background</h4>The possible association between β-adrenoceptor antagonists (β-blockers) and risk of COPD is controversial. The objective of the present study was to test whether β-blocker use is associated with susceptibility to the disease.<h4>Methods</h4>A total of 301,542 new users of β-blockers and 1,000,633 new users of any other antihypertensive drugs aged 30-90 years without any history of COPD hospitalizations were included in the present study and followed in the Danish National Pat ...[more]

PMID: 31193622

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Project description:BackgroundBeta-blocker therapies for cardiovascular comorbidities are often withheld in patients with chronic obstructive pulmonary disease (COPD) due to potential adverse effects on airway obstruction. We carried out a post hoc analysis to determine the efficacy and safety of aclidinium in patients with moderate-to-very severe COPD and increased cardiovascular risk receiving beta-blockers at baseline versus non-users.MethodsASCENT-COPD was a Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients were randomized 1:1 to aclidinium or placebo twice-daily for up to 3 years. Outcomes included risk of (time to first) major adverse cardiovascular events (MACE), all-cause mortality, and lung function over 3 years, and exacerbations over 1 year.ResultsOf 3589 patients, 1269 (35.4%) used beta-blockers and 2320 (64.6%) were non-users at baseline. Aclidinium did not statistically increase the risk of MACE (beta-blocker user: hazard ratio 1.01 [95% CI 0.62-1.64]; non-user: 0.80 [0.51-1.24]; interaction P = 0.48) or all-cause mortality (beta-blocker user: 1.13 [0.78-1.64]; non-user: 0.89 [0.62-1.26]; interaction P = 0.35), in patients using beta-blockers. Aclidinium reduced annualized rate of moderate-to-severe COPD exacerbation (beta-blocker user: rate ratio 0.75 [95% CI 0.60-0.94, P = 0.013]; non-user: 0.79 [0.67-0.93, P = 0.005]), delayed time to first exacerbation, and improved lung function versus placebo. There was greater trough FEV1 benefit in beta-blocker users versus non-users (least squares mean difference at 52 weeks: 111 mL [95% CI 74 mL-147 mL] versus 69 mL [42 mL-97 mL]; interaction P = 0.041).ConclusionsThis post hoc analysis supports long-acting anti-muscarinic use with concomitant beta-blockers in patients with moderate-to-very severe COPD and cardiovascular comorbidity.Trial registrationClinicalTrials.gov, NCT01966107, Registered 16 October 2013, https://clinicaltrials.gov/ct2/show/NCT01966107 .

Project description:AimsThe aim of this study was to clarify the effect of β-blockers (BBs) on respiratory function and survival in patients with chronic obstructive pulmonary disease with cardiovascular disease (CVD), as well as the difference between the effects of cardioselective and noncardioselective BBs.Methods and resultsWe searched for relevant literature in four electronic databases, namely, PubMed, EMBASE, Cochrane Library, and Web of Science, and compared the differences in various survival indicators between patients with chronic obstructive pulmonary disease taking BBs and those not taking BBs. Forty-nine studies were included, with a total sample size of 670 594. Among these, 12 studies were randomized controlled trials (RCTs; seven crossover and five parallel RCTs) and 37 studies were observational (including four post hoc analyses of data from RCTs). The hazard ratios (HRs) of chronic obstructive pulmonary disease exacerbation between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.77 [95% confidence interval (CI) 0.67, 0.89], 0.72 [95% CI 0.56, 0.94], and 0.98 [95% CI 0.71, 1.34, respectively] (HRs <1 indicate favouring BB therapy). The HRs of all-cause mortality between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.70 [95% CI 0.59, 0.83], 0.60 [95% CI 0.48, 0.76], and 0.74 [95% CI 0.60, 0.90], respectively (HRs <1 indicate favouring BB therapy). Patients with Chronic obstructive pulmonary disease treated with cardioselective BBs showed no difference in ventilation effect after the use of an agonist, in comparison with placebo. The difference in mean change in forced expiratory volume in 1 s was 0.06 [95% CI -0.02, 0.14].ConclusionThe use of BBs in patients with chronic obstructive pulmonary disease is not only safe but also reduces their all-cause and in-hospital mortality. Cardioselective BBs may even reduce chronic obstructive pulmonary disease exacerbations. In addition, cardioselective BBs do not affect the action of bronchodilators. Importantly, BBs reduce the heart rate acceleration caused by bronchodilators. BBs should be prescribed freely when indicated in patients with chronic obstructive pulmonary disease and heart disease.

Dataset Information

?-Blocker Therapy and Risk of Chronic Obstructive Pulmonary Disease - A Danish Nationwide Study of 1·3 Million Individuals.

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β-Blocker Therapy and Risk of Chronic Obstructive Pulmonary Disease - A Danish Nationwide Study of 1·3 Million Individuals.

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