Comparison of Long-Term Clinical Implications of Beta-Blockade in Patients With Obstructive Airway Diseases Exposed to Beta-Blockers With Different β1-Adrenoreceptor Selectivity: An Italian Population-Based Cohort Study.

Maurizio Sessa,Magnus Thorsten Jensen,Kristian Kragholm,Annalisa Capuano,Ilaria Perone,Cristina Scavone,Annamaria Fucile,Daniel Bech Rasmussen,Francesco Rossi,Liberata Sportiello,Antonella De Angelis,Annamaria Mascolo,Michele Tari,Annalisa Di Giorgio

doi:10.3389/fphar.2018.01212

Abstract

Rationale: Long-term clinical implications of beta-blockade in obstructive airway diseases remains controversial. We investigated if within the first 5 years of treatment patients with heart failure and obstructive airway diseases using non β1-adrenoreceptor selective beta-blockers have an increased risk of being hospitalized for all-causes, heart failure, and chronic obstructive pulmonary disease (COPD) when compared to patient using selective beta-blockers.Methods: Carvedilol users were propensity matched 1:1 for co-treatments, age, gender, and year of inclusion in the cohort with metoprolol/bisoprolol/nebivolol users. Cox proportional hazard regression model was used to compare all causes, COPD, and heart failure hospitalization or the beta-blocker discontinuation between cohorts. For statistically significant associations, we computed the rate difference and the attributable risk.Results: Overall, 11,844 patients out of the 51,214 (23.1%) were exposed to carvedilol and 39,370 (76.9%) to metoprolol/bisoprolol/nebivolol. Carvedilol users had a higher hazard for heart failure hospitalization (HR 1.29; 95% Confidence Interval [CI] 1.18–1.40) with 106 (95%CI 76–134; p-value < 0.001) additional cases of heart failure hospitalization per 10000 person-years if compared to metoprolol/bisoprolol/nebivolol users. In all, 26.8% (95%CI 22.5–30.9%; p-value < 0.001) of heart failure hospitalizations in the study population could be attributed to being exposed to carvedilol. Carvedilol users had a higher hazard (HR 1.06; 95%CI 1.02–1.10) of discontinuing the pharmacological treatment with 131 (95%CI 62–201; p-value < 0.001) additional cases of beta-blocker discontinuation per 10000 person-years metoprolol/bisoprolol/nebivolol users. In all, 6.5% (95%CI 3.9–9.0%; p-value < 0.001) of beta-blocker discontinuation could be attributed to being exposed to carvedilol.Conclusion: On long-term follow-up period, carvedilol was associated with a higher risk of heart failure hospitalization and discontinuation if compared to metoprolol/bisoprolol/nebivolol users among patients with heart failure and obstructive airway diseases.

Highlights

Beta-blockers are able to reduce mortality in patients with concurrent heart failure and respiratory diseases and, the co-existence of both diseases should not discourage the clinicians from using these drugs (Rutten et al, 2010; Short et al, 2011; Du et al, 2014; Lim et al, 2017)
Baseline characteristics of men and women were compared using the t-tests for continuous variables and χ2 test In Caserta Local Health Unit (Italy) administrative databases, we identified 51,214 patients exposed to β-blockers for heart failure concurrently with obstructive airway diseases drugs (ATC R03)
This study provided evidence on the impact of long-term beta-blocker administration for all causes, chronic obstructive pulmonary disease (COPD), heart failure hospitalization or beta-blocker discontinuation within the first 60 months of treatment for carvedilol and metoprolol/bisoprolol/nebivolol users co-treated with drugs for COPD or asthma

Summary

Introduction

Beta-blockers are able to reduce mortality in patients with concurrent heart failure and respiratory diseases and, the co-existence of both diseases should not discourage the clinicians from using these drugs (Rutten et al, 2010; Short et al, 2011; Du et al, 2014; Lim et al, 2017). European Society of Cardiology (ESC) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) clinical guidelines recommended more selective β1-adrenoreceptor antagonist in patients with concurrent heart failure and respiratory diseases (i.e., COPD and asthma) (Dickstein et al, 2008, 2010; McMurray et al, 2012; Ponikowski et al, 2016). The majority of studies comparing β1-selective and non-selective beta-blockers in patients with heart failure and concurrent respiratory diseases focused on short-term follow-up period post beta-blockers initiation and only a few studies provided outcomes of public health interest (Salpeter et al, 2002; Hawkins et al, 2009; Jabbour et al, 2010; Rutten et al, 2010; Dungen et al, 2011; Lainscak et al, 2011; Etminan et al, 2012; Kubota et al, 2015; Ponikowski et al, 2016; Sessa et al, 2017a). In the later phases, when patients are symptomatically stable, there is a tendency to preserve a stable posological schema (Dickstein et al, 2008, 2010; McMurray et al, 2012; Ponikowski et al, 2016)

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