In an observational study of patients who were prescribed varenicline (Chantix in the United States/Champix elsewhere, Pfizer) to stop smoking, treatment was associated with increased risk of cardiovascular events, researchers report. Patients in Ontario who visited the emergency room (ER) or were hospitalized for a cardiovascular event(MI or stroke) within a year before or after filling the first prescription for varenicline were 34% more likely to have this event during the 12-week varenicline-therapy period as opposed to before or after.

The patients who visited the ER or were hospitalized for a neuropsychiatric event (self-harm or a bipolar episode)—within the 2 years surrounding their first prescription for varenicline were 6% more likely to have this event during the therapy period; however, in this case, the increased risk was not significant.These findings, by Dr. Andrea S Gershon et al, were published online in the American Journal of Respiratory and Critical Care Medicine.

"I don't think this study is about that we shouldn't use varenicline for smoking cessation," Gershon cautioned, since quitting smoking has many established health benefits, including a significantly reduced risk of heart disease and cancer.

Moreover, "varenicline has been shown to increase the odds of quitting smoking by almost three times, and quitting smoking significantly reduces the risk of having a cardiovascular event—especially among those with a history of cardiovascular disease,"

However, "it is very important that physicians and patients not conclude from this study that varenicline causes a higher risk of cardiovascular disease," Dr Neha J Pagidipati (Duke University) emphasized, "because that is not what this study shows."

In randomized clinical trials, varenicline improved smoking-cessation rates more effectively than bupropion, nicotine replacement, nonpharmacological methods, and placebo. However, there have been conflicting reports about a possible link with adverse cardiovascular and neuropsychiatric events.

To investigate this, the researchers analyzed data from 56,851 Ontario residents who were 65 or older or on social assistance or in long-term care and thus covered by the provincial drug benefit plan when they were newly prescribed varenicline between September 2011 and February 2014.

The researchers compared cardiovascular and neuropsychiatric outcomes during 12 weeks after the prescription for varenicline was filled vs the control period, which was 1 year before starting varenicline until 1 year later (excluding the 12 weeks of varenicline therapy and 6-week induction period prior to this).

Of the more than 56,000 patients newly prescribed varenicline, 4185 patients had 5569 cardiovascular events and 4720 patients had 9460 neuropsychiatric events during the 2 years surrounding their varenicline therapy, excluding events that occurred during the induction period.

Overall, the incidence of cardiovascular events was significantly higher during the 12 weeks of varenicline therapy compared with the control period (relative incidence [RI] 1.34; 95% CI 1.25–1.44).

In contrast, the overall incidence of neuropsychiatric events was higher during varenicline therapy vs the control period (RI 1.06; 95% CI 1.00–1.13), but because the lower value of the confidence interval was 1.00, this was not significant.

Need Individualized Stop-Smoking Strategies

Nevertheless, Gershon said, "We hope that physicians will be able to incorporate this into the rest of the literature and inform their patients of this possible risk so that they can make informed decisions."

Pagidipati agreed that "quitting smoking is a difficult process and requires an open and honest dialogue between patient and provider to determine what strategy will work best for each individual."