SESSION TITLE: COPD Safety of Treatment Posters
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM
PURPOSE: Patients with COPD often require maintenance medications for effective disease management and suffer from cardiovascular (CV) comorbidities. It is thus essential to evaluate the long-term CV safety profile of COPD treatments intended for this population. Aclidinium bromide (ACL) is a long-acting muscarinic antagonist indicated for maintenance treatment of COPD-associated bronchospasm. The CV safety profiles for ACL 400µg BID, the approved dose, from all three phase 3, long-term safety studies in patients with moderate to severe COPD are presented.
METHODS: CV adverse events (AEs) for ACL from 2 pooled double-blind (DB) (LAS-MD-35 and LAS-MD-36; 52 wks each) and 1 open-label (OL) study (LAS-MD-38, Part B; 40 wks) were included. The major adverse CV event (MACE) composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke was assessed. Deaths were evaluated by an expert external adjudication committee blinded to study treatment.
RESULTS: Approximately 30% of the 443 (DB) and 448 (OL) patients treated with ACL had a history of cardiac disorders (eg, coronary artery disease) and >50% suffered from hypertension at baseline despite exclusion of patients with a clinically significant CV condition (eg, MI ≤6 months of screening). Furthermore, ≥30% of patients were taking CV medications (lipid-modifying agents/antithrombotics) prior to study entry. The MACE composite scores of serious events were low (DB, n=6, 1.4%; OL, n=7, 1.6%). One CV death was reported in the DB studies; 2 were reported in the OL trial. Nonfatal MI and nonfatal stroke were reported in similar patient percentages in the DB (MI: n=3, 0.7%; stroke: n=2, 0.5%) and OL (MI: n=2, 0.4%; stroke, n=4, 0.9%) studies. MACE composite score for all events for the DB & OL studies combined was n=18 (2.0%). Few cardiac AEs were observed, with any specific event reported by <1% of patients in either the DB or OL studies. Cumulative incidences for standardized MedDRA queries in the DB & OL studies, respectively, were 1.4% & 3.6% for ischemic heart disease, 0.7% & 0.7% for supraventricular tachyarrhythmia, 0.7% & 1.1% for cardiac failure, and 2.3% & 0.4% for bradyarrhythmia/conduction defect/sinus node disorder.
CONCLUSIONS: In this population, CV events were infrequent with up to 52 weeks of treatment with DB and OL ACL treatment.
CLINICAL IMPLICATIONS: No clear cardiac safety signal was observed with long-term ACL treatment in these studies. The generalizability of these findings to patients at high risk for CV events needs to be further evaluated.
DISCLOSURE: James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Novartis, GlaxoSmithKline, Boehringer-Ingelheim, Forest, and Pfizer Donald Tashkin: Other: Donald Tashkin has served as an advisor to and received clinical research funding from Forest, Boehringer-Ingelheim, Novartis, Pearl Therapeutics and Sunovion , served as a consultant to Theravance, received additional research funding from GlaxoSmithKline, and served as a speaker for Forest, Boehringer-Ingelheim, Pfizer, AstraZeneca and Novartis Gary Ferguson: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Forest, Sunovian and Pearl, Grant monies (from industry related sources): Boehringer-Ingelheim, Forest, GlaxoSmithKline, Novartis and Pearl Peter Kowey: Consultant fee, speaker bureau, advisory committee, etc.: Consultant for Forest Ludmyla Rekeda: Employee: Forest Research Institute Pomy Shrestha: Employee: Forest Research Institute Esther Garcia Gil: Employee: Almirall S.A. Cynthia Caracta: Employee: Forest Research Institute
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