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: Assessing cardiovascular (CV) safety of COPD treatments is important due to high prevalence of CV comorbidities. Aclidinium (ACL) is a long-acting muscarinic antagonist indicated for maintenance treatment of COPD-associated bronchospasm. CV safety was evaluated from 3 clinical trials of ACL in moderate to severe COPD patients.
METHODS: CV events were pooled from ACCORD COPD I and II (12 wks each) and ATTAIN (24 wks). Deaths were adjudicated by external committee blinded to treatment. Major adverse CV event (MACE) composite (CV death, nonfatal myocardial infarction [MI], nonfatal stroke) was assessed in each group (ACL 200µg, 400µg, or placebo [PBO] BID). Results for the approved 400μg dose vs PBO are presented.
RESULTS: In these studies, (PBO n=641; ACL n=636), although patients with clinically significant CV conditions (eg, MI ≤6 months of screening) were excluded, ~25% of patients had history of cardiac disorders (eg, stable coronary artery disease); >25% of patients took prior CV medications (lipid modifiers/antithrombotics); 13% took β-blockers (all continued in studies). MACE composite scores of serious events were equal for ACL and PBO (n=2;0.3%). One CV death (acute cardiac failure, not considered treatment related) occurred with ACL (0.2%; patient had history of heart disease); 1 nonfatal MI occurred with PBO (0.2%), and 1 patient (0.2%) in each group had nonfatal stroke. Two nonfatal strokes with PBO were the only nonserious MACE events. Cardiac standardized MedDRA query (SMQ) AEs occurred infrequently (PBO 2.7%; ACL 3.0%); cerebrovascular SMQ AEs occurred rarely (PBO 0.5%; ACL 0.2%). Supraventricular tachyarrhythmia&ischemic heart disease occurred in 0.6%&0.9% of PBO and 0.2%&0.5% of ACL patients (incidence ratio [95% CI]:0.25[0.03-2.20]&0.48[0.12-1.96]). Bradyarrhythmia/conduction defect/sinus node disorder incidences (2.31[0.82-6.55]) were imbalanced between PBO (0.8%) and ACL (1.6%) due in part to higher baseline incidence of nonserious conduction defects (ACL). Numerical imbalance in cardiac failure was seen between PBO (0.3%) and ACL (0.8%;2.86[0.58-14.07]); none was considered treatment related.
CONCLUSIONS: CV events were infrequent in COPD patients with up to 24 weeks of ACL and generally similar to PBO.
CLINICAL IMPLICATIONS: In this pooled population, similar CV safety profiles between ACL and PBO suggest an absence of cardiac safety signal with up to 6 months of ACL treatment in COPD patients. Generalizability of these data to patients at high risk for CV events needs to be further evaluated.
DISCLOSURE: 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 Edward Kerwin: Other: Edward Kerwin has received travel reimbursement from Merck, Forest, and Novartis, and has performed multicenter clinical trials for multiple pharmaceutical companies including Forest and Almirall S.A. David Singh: Consultant fee, speaker bureau, advisory committee, etc.: from various pharmaceutical companies including AstraZeneca, GlaxoSmithKline, Chiesi, Boehringer Ingelheim and Roche 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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