Journal Article

Risk Assessment of Acute Myocardial Infarction and Stroke Associated with Long-Acting Muscarinic Antagonists, Alone or in Combination, versus Long-Acting beta2-Agonists

Lei, Alejhandra, Rivero-Ferrer, Elena, Rubino, Annalisa, Martinez, David, Saigi-Morgui, Nuria, Aguado, Jaume, Daoud, Sami, Plana, Estel, Rebordosa, Cristina, Perez-Gutthann, Susana

2022

Overview

Background: The long-acting muscarinic antagonist (LAMA) aclidinium was approved in Europe in 2012 to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). A post-authorization safely study was initiated to assess potential cardiovascular risks associated with LAMAs versus long-acting beta2-agonists. Purpose: To estimate incidence rates and adjusted incidence rate ratios (IRRs) for acute myocardial infarction (AMI), stroke, and major adverse cardiac events (MACE) in new users of aclidinium, aclidinium/fonnoterol, tiotropium, other LAMA, long- acting beta-agonists/inhaled corticosteroids (LABA/ICS), and LAMA/LABA compared with initiators of LABA. Patients and Methods: This population-based cohort study included patients with COPD aged [greater than or equal to] 40 years initiating COPD medications in the UK Clinical Practice Research Datalink (CPRD) Auram database from 2012 to 2019. Poisson regression models were used to estimate the IRR for AMI, stroke, and MACE in users of COPD medications versus LABA, adjusting for clinically relevant covariables. Results: The study included 11,121 new users of aclidinium, 4804 of aclidinium/fonnoterol, 56,198 of tiotropium, 23,856 of other LAMA, 17,450 of LAMA/LABA, 70,289 of LABA/ICS, and 13,716 of LABA. During periods of continuous medication use after initiation (current use), crude incidence rates per 1000 person-years for AMI ranged from 8.7 (aclidinium/fonnoterol) to 12.4 (LAMA/ LABA), for stroke ranged from 4.8 (aclidinium/fonnoterol) to 7.2 (LAMA/LABA), and for MACE ranged from 13.5 (aclidinium/ fonnoterol) to 19.3 (LAMA/LABA). Using LABA as reference, adjusted IRRs [95% confidence intervals] were close to 1 for all study drugs for AMI (lowest for aclidinium/fonnoterol, 0.95 [0.60-1.52], and highest for LAMA/LABA, 1.23 [0.91-1.67]), stroke (lowest for aclidinium/fonnoterol, 0.64 [0.39-1.06], and highest for tiotropium, 1.02 [0.81-1.27] for tiotropium) and for MACE (lowest for aclidinium, 0.93 [0.75-1.16], and highest for LAMA/LABA, 1.24 [0.97-1.59]). Conclusion: Risks of AMI, stroke, and MACE in current users of aclidinium, aclidinium/fonnoterol, tiotropium, other LAMA, LAMA/LABA, or LABA/ICS were similar to the risks among current users of LABA. Keywords: aclidinium, acute myocardial infarction, LAMA, stroke, United Kingdom

• Publisher: Dove Medical Press Limited,Dove Medical Press Ltd,Dove Press,Dove,Dove Medical Press
• Subject: aclidinium / Aclidinium bromide / acute myocardial infarction / Angina pectoris / Body mass index / Cardiac arrhythmia / Cardiovascular disease / Cardiovascular diseases / Cerebrovascular disease / Chronic obstructive pulmonary disease / Codes / Coma / Comparative analysis / Congenital diseases / Drug dosages / Heart attack / Heart attacks / Heart failure / HIV / Hospitalization / Human immunodeficiency virus / Human subjects / Immune system / Indacaterol / Kidney diseases / LAMA / Lung diseases, Obstructive / Medical research / Medicine, Experimental / Original Research / Patients / Pharmaceutical industry / Risk assessment / Steroids / Stroke / Stroke (Disease) / Tiotropium / United Kingdom