EFFICACY AND SAFETY OF VARENICLINE FOR SMOKING CESSATION IN PATIENTS WITH MILD TO MODERATE COPD

Abstract

PURPOSE: Smoking is the most important cause of Chronic Obstructive Pulmonary Disease (COPD) and accelerates its progression. Finding effective smoking cessation interventions for this population is paramount. The primary objective of this randomized clinical trial was to compare the efficacy and safety of varenicline versus placebo in smokers with mild moderate COPD. METHODS: In a 27 center, double-blind, multinational study, patients with mild moderate COPD (post-bronchodilator FEV1/FEV <70% and FEV1 % predicted normal value [≥]50%) were randomized to receive varenicline (titrated to 1 mg BID) or placebo for 12 weeks, with a 40-week non-treatment follow-up. The primary endpoint was carbon monoxide (CO)-confirmed continuous abstinence rate (CAR) for Weeks 9 12. A secondary endpoint was CAR for Weeks 9 52. Adverse events (AEs) and safety parameters were monitored. RESULTS: Mean ({+/-} SD) baseline characteristics for all subjects were: age 57.1 (9.1) yrs; FEV1 2.28 (0.66) Liters; post- bronchodilator FEV1 69.9 (16.9) % pred; number cigs/day over past month 24 (11); smoking duration 41 (9) yrs; age commenced smoking 16 (4) yrs; Fagerstrom Test for Nicotine Dependence score 6.1 (2.2). 62.3% of participants were male and 83.0% Caucasian. Randomized and treated patients were included in the efficacy and safety analysis (varenicline, n=248; placebo, n=251). Week 9 12 CAR was significantly higher for varenicline (42.3%) versus placebo (8.8%; p<0.0001; OR=8.40; 95% CI, 4.99, 14.14). Greater varenicline efficacy was maintained during Weeks 9 52 (varenicline CAR 18.6% vs placebo CAR 5.6%; p<0.0001; OR=4.04; 95% CI, 2.13, 7.67). Nausea, abnormal dreams, and insomnia were the most commonly reported AEs for varenicline. Serious AEs occurred in 2.8% varenicline participants and 4.4% placebo participants. Two varenicline patients and one placebo patient died during the study. One suicidal ideation event was reported for placebo; no such event was reported for varenicline. Reports of depression, depressed mood, and depressive symptoms were similar for both treatment groups. CLINICAL IMPLICATIONS: Varenicline is an efficacious and well tolerated pharmacologic treatment for smoking cessation among patients with mild moderate COPD. DISCLOSURE: Non-Industry Grants: Dr. Donald Tashkin has received grant monies from NHLBI. Dr. Stephen Rennard has received grant monies from Nebraska Department of Health and Human Services and IFSH. Dr. J. Taylor Hays has received grant monies from: Veterans Administration; American Legacy Foundation and Mayo Foundation for Medical Education and Research. Industry Grants: Dr. Donald Tashkin has received grant monies from: Boehringer-Ingelheim; Schering-Plough, Dey Labs, GlaxoSmithKline; Novartis and AstraZeneca. Dr. Stephen Rennard has received grant monies from: Almirall; Atlanta; Astellas; AstraZeneca; Biomarck; Centocor; CSL Beling GMBH; GlaxoSmithKline; Lorrillard; MPex Pharmaceuticals; Nabi; Novartis; Otsuka Maryland Research Institute; Pearl Therapeutics; Pfizer; Philip Morris; Reynolds; Roche; Schering-Plough; Talecris and Wyeth Pharmaceuticals. Dr. J. Taylor Hays has received grant monies from Eli Lilly. Shareholder: Dr. Theodore C. Lee is a stockholder at Pfizer Inc. Employee: Dr. Theodore C. Lee is a Medical Director at Pfizer Inc. Wendy Ma is employed as a statistician at Pfizer Inc. Consultant fee, speaker bureau, advisory committee, etc: Dr. Donald Tashkin is a speaker for Boehringer-Ingelheim; Pfizer; AsraZeneca; Dey Labs and GlaxoSmithKline and an Ad Board Member for Beohringer-Ingelheim and AstraZeneca. Dr. Stephen Rennard is a Speaker for AstraZeneca; Boehringer Ingelheim; GlaxoSmithKline; Otsuka; Pfizer and SOMA and has been a consultant or Ad Board member for Abbott; Adams; Almirall; Atlana; Aradigm; AstraZeneca; Bend; Biolipox; Centocor; Critical Therapeutics; Dey; GlaxoSmithKline; ICOS; Johnson & Johnson; Novartis; Nycomed; Ono Pharma; Parengenix; Pfizer; Roche; Sankyo; Sanofi; Schering-Plough; Theravance and UBS.