Despite concerns that certain smoking cessation therapies may increase the risk of cardiovascular events, a study published online Dec. 9 in Circulation found no such association.

The worry over the three approved smoking cessation therapies—buproprion (Wellbutrin, GlaxoSmithKline), varenicline (Chantix, Pfizer) and nicotine replacement therapy (NRT)—arose after a 2011 analysis found varenicline linked to an increased risk of cardiovascular events. The finding gained the attention of both the media and the FDA. However, a follow-up analysis found the effects to be nonsignificant compared to placebo.

“Recognizing the large number of smokers attempting to quit by using pharmacotherapies, and the widespread media reports of cardiovascular risks associated with pharmacotherapies, making clear public health messages remains a priority,” wrote the authors, led by Edward J. Mills, PhD, MSc, of Stanford University School of Medicine in Stanford, Calif.

Mills and his colleagues analyzed 63 randomized clinical trials (involving more than 30,000 participants) evaluating the cardiovascular risks related to buproprion, varenicline and NRT. As endpoints, they looked at any cardiovascular events that other meta-analyses associated with these therapies and major adverse cardiovascular events (MACE).

Their analysis revealed no association between buproprion and the risk of any cardiovascular events (relative risk [RR] 0.98). They also found no association between varenicline and the risk of cardiovascular events (RR 1.30). NRT did increase the risk of minor cardiac events, such as tachycardia (RR 2.29).

In terms of MACE, buproprion protected against these outcomes (RR 0.45) and the other two therapies did not increase the risk of these events (RR 1.34 for varenicline and 1.95 for NRT).

The authors acknowledged that a major limitation of their analysis was that it involved patients who were fairly healthy overall, so their findings may not be generalizable to everyone using these therapies.

However, they argued that the risks should be considered alongside the significant benefits of quitting smoking.

“Concerns about adverse events need to be balanced with the consistent evidence for the benefit of smoking cessation and patients should be counseled about what adverse events may be associated with smoking cessation therapies, the symptoms associated with the withdrawal period from cigarettes, and symptoms that may be due to existing diseases,” the researchers wrote.