Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease - Efficacy and Safety of Varenicline


The goal of the trial was to evaluate smoking cessation treatment with varenicline (Chantix), a partial α4β2 nicotinic acetylcholine receptor agonist, compared with placebo among patients with stable coronary disease.


Varenicline would be more effective in smoking cessation.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patients Screened: 858
Patients Enrolled: 714
Mean Follow Up: 52 weeks
Mean Patient Age: 57 years
Female: 25

Patient Populations:

  • Patients 35-75 years of age who had smoked at least 10 cigarettes daily for the last year
  • Stable coronary artery disease diagnosed at least 2 months ago


  • Cardiovascular procedure in the last 2 months
  • Any sign of cardiovascular instability
  • Uncontrolled hypertension
  • Significant cerebrovascular disease
  • Prior amputation from peripheral arterial disease
  • Severe congestive heart failure
  • Severe chronic obstructive pulmonary disease
  • Severe renal, hepatic, endocrine, or gastrointestinal disease
  • Cancer
  • Depression or treatment with antidepressants in the last month
  • Psychosis, panic, or bipolar disorder
  • Drug or alcohol dependence
  • Concurrent smoking cessation medication use including nicotine replacement therapy, bupropion, clonidine, or nortriptyline

Primary Endpoints:

  • Continuous abstinence rate for weeks 9-12

Drug/Procedures Used:

In addition to smoking-cessation counseling, patients with stable coronary disease were randomized to varenicline 1 mg twice daily (n = 355) versus placebo (n = 359) for 12 weeks.

Principal Findings:

Overall, 714 patients were randomized. There was no difference in baseline characteristics between the groups. In the varenicline group, the mean age was 57 years, 25% were women, body mass index was 27.5 kg/m2, mean duration of smoking was 40 years, mean number of cigarettes per day was 22.1, and the proportion of patients with previous serious attempts to quit smoking was 85.6%. Prior myocardial infarction was present in 45.9%, prior coronary revascularization in 46.2%, prior stroke in 4.5%, and peripheral arterial disease in 23.1%.

The continuous abstinence rate at 9-12 weeks was 47.0% for varenicline versus 13.9% for placebo (p < 0.0001). Abstinence diminished over time, although it was still better with varenicline. At 9-24 weeks, abstinence was 28.2% versus 9.5% (p < 0.001) and at 9-52 weeks, abstinence was 19.2% versus 7.2% (p < 0.001), respectively, for varenicline versus placebo.

All-cause mortality was 0.6% versus 1.4%, cardiovascular mortality was 0.3% versus 0.6%, and any cardiovascular event was 7.1% versus 5.7% (p = NS for all comparisons), respectively, for varenicline versus placebo. Study medication was stopped for an adverse event in 9.6% of the varenicline group versus 4.3% of the placebo group (p < 0.05). The most frequently reported adverse events were nausea (29.5% vs. 8.6%), vomiting (8.2% vs. 1.1%), insomnia (11.9% vs. 6.6%), abnormal dreams (7.9% vs. 1.7%), and constipation (6.5% vs. 2.0%), respectively, for varenicline versus placebo.


Among patients with stable coronary artery disease, the use of varenicline was effective at improving rates of smoking cessation compared with placebo. This was most evident from 9-12 weeks; however, it was also seen at 24-52 weeks. Cardiovascular outcomes were similar between the groups, although varenicline was associated with more gastrointestinal and sleep disturbances.

Varenicline has predominately been studied in otherwise healthy participants; therefore, the safety profile of this agent in individuals with documented coronary artery disease was unknown. Although not definitive, this trial documents that varenicline may be safe for use among individuals with stable coronary artery disease.


Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation 2010;121:221-9.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism

Keywords: Nausea, Coronary Artery Disease, Myocardial Infarction, Sleep Initiation and Maintenance Disorders, Vomiting, Stroke, Behavior Therapy, Receptors, Nicotinic, Counseling, Peripheral Arterial Disease, Quinoxalines, Benzazepines, Body Mass Index, Constipation, Nicotinic Agonists, Smoking Cessation

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