Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial

Abstract

Objective To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit. Design Double blind, placebo controlled, parallel group, multicentre, randomised controlled trial. Setting Medical clinics (mostly primary care) in Norway and Sweden. Participants Men and women aged ≥18 who used smokeless tobacco at least eight times a day, with no abstinence period over three months within one year before screening, who wanted to quit all tobacco use. Participants were excluded if they used any other form of tobacco (except smokeless tobacco) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition. Interventions Varenicline 1 mg twice daily (titrated during the first week) or placebo for 12 weeks, with 14 weeks' follow-up after treatment. Main outcome measures The primary end point was the four week continuous abstinence rate at the end of treatment (weeks 9-12) confirmed with cotinine concentration. A secondary end point was continuous abstinence rate for weeks 9-26. Safety and tolerability were also evaluated. Results 431 participants (213 varenicline; 218 placebo) were randomised and received at least one dose of study drug. Participants' demographics and baseline use of smokeless tobacco were similar (89% (189) and 90% (196), respectively, were men; mean age in both groups was 43.9; participants used smokeless tobacco products about 15 times a day, and about 80% first used smokeless tobacco within 30 minutes after awakening). Continuous abstinence rate at week 9-12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, P<0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9-26 was 45% (95) v 34% (73); relative risk 1

Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…After the removal of duplicates and screening of titles and abstracts, 68 trials underwent full‐text review. In total, 38 RCTs met all eligibility criteria and were included in our meta‐analysis 10, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49…”

Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis

“…Fourteen double-blind placebo-controlled trials were included in the meta-analysis. 9,[16][17][18][19][20][21][22][23][24][25][26][27][28] An additional open-label trial of varenicline versus nicotine replacement therapy was included in the sensitivity analysis. 29 Characteristics of the trials are summarized in Table 1 and Appendix 2 (available at www .cmaj.ca /lookup /suppl /doi:10.1503 /cmaj .110218 /-/DC1).…”

“…All but one of the trials enrolled smokers; the remaining trial enrolled people who used smokeless tobacco. 18 The primary outcome was the continuous abstinence rate in 12 trials, 9,[16][17][18][19][20][21][22][23][24][25]27 the long-term quit rate in 1 trial 26 and long-term safety in 1 trial. 28 All but one of the trials excluded patients with a history of cardiovascular disease; the remaining trial included participants with stable cardiovascular disease but excluded those with unstable cardiovascular disease.…”

“…21,23,24 Details of the risk-of-bias assessment appear in Table 2 and Appendix 3 (available at www .cmaj.ca /lookup /suppl /doi:10.1503 /cmaj .110218 /-/DC1). Nine RCTs were judged to be at low risk of bias (adequate sequence generation, allocation concealement and double blinding, and clear reporting of withdrawal rates); 9,[18][19][20][21][22][23]26,27 the remaining five RCTs were at unclear risk of bias owing to incomplete reporting of randomization. 16,17,24,25,28 The openlabel trial had an unclear risk of bias.…”

“…*All but one of the trials involved smokers; the study by Fagerstrom et al 18 involved users of smokeless tobacco. Additional study characteristics are available in Appendix 2 (www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.110218/-/DC1).…”