quitting smoking

A recent clinical trial investigated the safety of the three most commonly used drugs for quitting smoking: nicotine-replacement therapy, varenicline, and bupropion.

Cigarette smoking is a major cause of cardiovascular disease. Patients who smoke have an increased risk of heart attack, stroke, diseases of blood vessels outside the heart, atrial fibrillation, sudden cardiac death, worsening heart failure, and a higher risk of blood clots following revascularization. The US Public Health Service Clinical Practice Guidelines for Smoking Cessationrecommend that healthcare practitioners should offer behavioural support and medical treatment with drugs to help patients succeed at quitting smoking.

Common medications for quitting smoking

The three most commonly used medications for quitting smoking include nicotine-replacement therapy (Nicoderm, Nicorette, Habitrol), varenicline (Champix or Chantix), and bupropion (Zyban). All three drugs may affect cardiac health. Nicotine increases heart rate, blood pressure, and cardiac work. Bupropion may increase heart rate and blood pressure. Varenicline may also have effects on the function and regeneration of the cells lining the blood vessel walls, thus contributing to cardiac adverse events.


Researchers from the Department of Medicine at the University of California conducted a randomized clinical trial to evaluate and compare the cardiac effects of these three drugs. The results were published in JAMA Internal Medicine.

The researchers used an already existing study to gather clinical data on the effects of drugs that help with quitting smoking. The researchers extended the trial, named EAGLES(Evaluating Adverse Events in a Global Smoking Cessation Study), to follow patients for up to 52 weeks.

The trial did not find any significant differences among the drugs

The first outcome the researchers investigated was the time to a major adverse cardiac event (MACE). A MACE was defined as cardiovascular death, non-fatal heart attack, or non-fatal stroke. The other outcomes they investigated were an occurrence of a MACE and a MACE+. A MACE+ included any MACE, new onset or worsening of peripheral vascular disease, coronary artery bypass, or hospitalization for the condition of the heart not getting enough blood flow and oxygen.

They included over 4000 patients in the analysis. For the primary and secondary outcomes, they did not find any significant differences between each treatment. During the 12-week treatment phase and follow-up period, there were no statistically significant differences between varenicline and bupropion treatment groups for the time to experience a MACE.

They also did not notice any differences when comparing the three different treatments for a MACE+. When comparing between each treatment group and comparing nicotine-replacement therapy with placebo for time to MACE and MACE+, they also did not notice any significant differences.

As expected, patients with high cardiovascular risk scores at the beginning of the study had the greatest risk of cardiovascular events during the trial. However, when comparing each treatment group, there were no differences in the incidence of cardiovascular events when evaluating according to low, medium, and high cardiovascular risk scores. One limitation of the study is the exclusion of patients with unstable cardiovascular disease. Therefore, these results cannot be extrapolated to this population.

Drugs to help quit smoking may be safe and effective

In conclusion, using these medications to support individuals to quit smoking is safe and effective. Healthcare practitioners should continue to offer counselling and medication for patients willing to try to quit smoking. The cardiovascular benefits of quitting smoking greatly outweigh the possible side effects of these medications.

Written by Jessica Caporuscio, PharmD

Reference: Benowitz NL, Pipe A, West R, et al. Cardiovascular Safety of Varenicline, Bupropion, and Nicotine. Patch in Smokers: A Randomized Clinical Trial. JAMA Intern Med. 2018.

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