Overall and Cardiovascular Safety of Aclidinium Bromide in Patients With COPD: A Pooled Analysis of Six Phase III, Placebo-Controlled, Randomized Studies

Abstract

Background: Aclidinium bromide, an M 3 -receptor-selective, twice-daily (BID), long-acting muscarinic antagonist, is rapidly hydrolyzed in human plasma, resulting in low systemic exposure and urinary excretion. We evaluated the overall and cardiovascular (CV) safety of aclidinium in patients with moderate to severe chronic obstructive pulmonary disease (COPD) by pooling data from 6 randomized, double-blind, placebo-controlled, parallel-group studies of ≥1 month's duration. Methods: Patients were current/former smokers aged ≥40 years with no history of clinically significant CV conditions. Treatment was administered (morning and evening) via Genuair TM /Pressair. ®a Adverse events (AEs), major adverse CV events (MACE), cardiac and cerebrovascular AEs, and serious AEs (SAEs) were analyzed. Results: The pooled population included 2781 patients (aclidinium: n=1529; placebo: n=1252). The incidence of AEs was similar with aclidinium (53.5%) and placebo (55.4%), as was the incidence of cardiac (aclidinium: 5.0%; placebo: 4.4%) and cerebrovascular (aclidinium: 0.4%; placebo: 0.5%) events. The incidence of MACE was low (AEs: 0.7%; SAEs: 0.5%) and comparable between groups. The incidence of cardiac and cerebrovascular events was similar for patients with CV risk factors with aclidinium and placebo (rate ratio [RR] [95%confidence interval (CI)]=1.01 [.074, 1.39]). In patients with mild to severe renal impairment, the incidence of cardiac events was similar between groups (RR [95% CI]=0.87 [0.56, 1.36]). Conclusion: Aclidinium 400µg BID has a good safety profile and this pooled analysis found no evidence of increased CV or cerebrovascular risk compared with placebo in patients with moderate to severe COPD. Further studies are needed in high-risk patients. AbstractAbbreviations: twice daily, BID; cardiovascular, CV; chronic obstructive pulmonary disease, COPD; adverse event, AE; major adverse cardiovascular event, MACE; serious adverse event, SAE; rate ratio, RR; confidence interval, CI; long-acting muscarinic antagonist, LAMA; Global initiative for chronic Obstructive Lung Disease, GOLD; dry-powder inhaler, DPI; Understanding Potential Long-term Impacts on Function with Tiotropium, UPLIFT trial; TIOtropium Safety and Performance in Respimat, TIOSPIR trial; chronic kidney disease, CKD; fixed-dose combination, FDC; once daily, QD; forced expiratory volume in 1 second, FEV1; Standardized MedDRA Queries, SMQ; preferred term, PT; myocardial infarction, MI; system organ class, SOC; angiotensin-converting enzyme, ACE; calcium ion, Ca 2+ ; standard deviation, SD Funding Support: The studies included in this pooled analysis were funded by Almirall S.A., Barcelona, Spain and Forest Laboratories LLC, a subsidiary of Actavis PLC, New York, New York. The pooled analysis was funded by Almirall S.A., Barcelona, Spain.

The Effect of Aclidinium on Symptoms Including Cough in Chronic Obstructive Pulmonary Disease: A Phase 4, Double-Blind, Placebo-controlled, Parallel-Group Study

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Effect of Aclidinium Bromide on Major Cardiovascular Events and Exacerbations in High-Risk Patients With Chronic Obstructive Pulmonary Disease

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