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 M3-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 GenuairTM/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.

SUBMITTER: Chapman KR 

PROVIDER: S-EPMC5559124 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature