Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial

Abstract

Importance: Some cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting.

Objective: To determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction.

Design, setting, and participants: Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising.

Interventions: Twenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks.

Main outcomes and measures: Primary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52.

Results: The varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07).

Conclusions and relevance: Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation.

Trial registration: clinicaltrials.gov Identifier: NCT01370356.

Figure 1

CONSORT Diagram ^aParticipants not randomized to study treatment due to reasons classified by the investigators as “other” included reasons such as: did not attend randomization visit; unable to commit to attending study visits; change in work schedule; change in concomitant medications; change in personal circumstances; and unavailability of urine drug screening kits. ^bTreatment phase was weeks 1 through 24. Includes 9 varenicline participants and 7 placebo participants who withdrew from the study before receiving study medication counted under the respective category for reasons of withdrawal. Note that one placebo participant stayed in the study although did not take any study medication, also see ^d. Discontinuations from study due to reasons classified by the investigators as “other” included reasons such as: new job or change in work schedule; moved out of area; change in personal or family circumstances; and unwilling or unable to attend visits. ^cInsufficient clinical response was a prepopulated option chosen by the investigators on the case report forms. ^dIncludes 1 placebo participant who did not receive any study medication but completed the study. ^ePost-treatment follow-up phase was weeks 25 through 52. Discontinuations from study due to reasons classified by the investigators as “other” included reasons such as: new job or change in work schedule; moved out of area; change in personal or family circumstances; and unwilling or unable to attend visits.

Figure 2

7-Day Point Prevalence Smoking Abstinence and 95% Confidence Intervals Week 12 RD = 24.5%; 95% CI 20.8%, 28.3%; RR = 4.7; 95% CI 3.5, 6.2. Week 24 RD = 25.7%; 95% CI 21.2%, 30.1%; RR = 2.5; 95% CI 2.1, 3.0. Week 52 RD = 15.8%; 95% CI 11.5%, 20.2%); RR = 1.9, 95% CI 1.6, 2.2. Abbreviations: RD, risk difference; RR, relative risk; CIs, confidence intervals; N, all randomized participants.