Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital

Abstract

Background: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks.

Methods: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking.

Results: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI -0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI -3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI -7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference -0.7%, 95% CI -7.8% to 6.5%).

Interpretation: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573.

Figure 1:

Randomization and follow-up of study patients. *Includes all patients except those who died. For the intention-to-treat (ITT) analysis, patients who were lost to follow-up or withdrew were assumed to have returned to smoking at their baseline rate. †In the event of loss to follow-up, vital status was obtained from chart review if possible. ACS = acute coronary syndrome.

Figure 2:

Trends in point-prevalence smoking abstinence from baseline to week 52. All analyses were intention-to-treat. Patients who withdrew consent or were lost to follow-up were assumed to have returned to smoking at their baseline rate. Participants who died were censored after the time of death. Participants were considered abstinent if they abstained from smoking in the 7 days before the visit through a self-report of 0 cigarettes smoked per day, confirmed by exhaled carbon monoxide levels of 10 ppm or less at clinic visits (available for 94.7%, 87.3%, 79.7% and 81.7% of self-reported abstinent participants at weeks 4, 12, 24 and 52, respectively).

Figure 3:

Smoking cessation and reduction by treatment group. All analyses were intention-to-treat. Participants who withdrew consent or were lost to follow-up were assumed to have returned to smoking at their baseline rate. Participants who died were censored after the time of death. A) Smoking cessation: point-prevalence abstinence. Participants were considered abstinent if they abstained from smoking in the 7 days before the visit through a self-report of 0 cigarettes smoked per day, confirmed by exhaled carbon monoxide levels of 10 ppm or less (available for 94.7%, 87.3%, 79.7% and 81.7% of self-reported abstinent participants at weeks 4, 12, 24 and 52, respectively). Risk differences: 4 weeks, 22.3 (95% confidence interval [CI] 11.2 to 33.3); 12 weeks, 21.3 (95% CI 10.3 to 32.3); 24 weeks, 14.9 (95% CI 3.9 to 25.8); 52 weeks, 10.7 (95% CI 0.01 to 21.4). B) Smoking cessation: continuous abstinence. Participants were considered abstinent if they abstained from smoking through a self-report of 0 cigarettes smoked per day, confirmed by exhaled carbon monoxide levels of 10 ppm or less (available for 96.9%, 91.0%, 82.6% and 88.5% of self-reported continuously abstinent participants at weeks 4, 12, 24 and 52, respectively) at all follow-up visits. Risk differences: 4 weeks, 19.6 (95% CI 8.6 to 30.5); 12 weeks, 14.5 (95% CI 3.7 to 25.3); 24 weeks, 10.0 (95% CI −0.4 to 20.4); 52 weeks, 9.9 (95% CI −0.1 to 19.8). C) Reduction in daily cigarette consumption of 50% or more from baseline; self-report only. Risk differences: 4 weeks, 12.4 (95% CI 3.7 to 21.2); 12 weeks, 16.1 (95% CI 5.9 to 26.4); 24 weeks, 11.7 (95% CI 0.8 to 22.7); 52 weeks, 8.2 (95% CI −3.1 to 19.4). *Adjusted for loss to follow-up. †In self-reported daily cigarette consumption from baseline.