Varenicline for Smoking Cessation Linked to Cardiac Events

Marlene Busko

January 02, 2018

TORONTO, ON — 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[1].

Patients in Ontario who visited the emergency room (ER) or were hospitalized for a cardiovascular event—such as an MI or stroke—within a year before or after filling a 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.

Similarly, patients who visited the ER or were hospitalized for a neuropsychiatric event—such as 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 (University of Toronto, Ontario) and colleagues, were published online December 20, 2017 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 to | Medscape Cardiology, 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," the authors stress. Also, the small increased relative incidence of neuropsychiatric events was "of questionable clinical significance."

"If patients decide to go on varenicline, which I think is not going to be an unreasonable choice for many or most people," said Gerson, clinicians should monitor more closely, "to make sure that if there is anything that is going wrong, it's caught early."

Invited to comment, Dr Neha J Pagidipati (Duke University, Durham, North Carolina) told | Medscape Cardiology that "the article addresses an important issue, which is the real-world experience of varenicline users in diverse populations," and it shows the importance of physician-patient discussions about smoking cessation.

However, "it is very important that physicians and patients not conclude from this study that varenicline causes a higher risk of cardiovascular disease," she emphasized, "because that is not what this study shows."

Real-world Results

In randomized clinical trials, varenicline improved smoking-cessation rates more effectively than bupropion, nicotine replacement, nonpharmacological methods, and placebo, Gershon and colleagues write. 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).

The cardiovascular outcomes were acute MI, unstable angina, other ischemic heart disease, ischemic stroke, heart failure, cardiac dysrhythmias, and peripheral vascular disease that resulted in a visit to the ER or hospitalization.

The neuropsychiatric outcomes were intentional self-harm; depressive or bipolar episodes; psychotic, anxiety, neurotic, or stress-related disorders; insomnia; hallucinations; and signs/symptoms of hostility and/or agitation that led to a visit to the ER or hospitalization.

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).

There was also an increased relative risk of this outcome in subgroup analyses of men or women, patients younger or older than 65, and patients with or without a prior cardiovascular event.

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.

However, older patients (>65) had a significantly increased risk of a neuropsychiatric event, mainly anxiety or mood disorders requiring an ER visit or hospitalization, during the 12-week varenicline-therapy period.

Need Individualized Stop-Smoking Strategies

"This study looked only at people who actually had a cardiovascular event," Pagidipati stressed, "and then went back and tried to determine whether that event was more likely to happen near the time that they first started taking varenicline or not."

It is also important to remember that this is an observational study, and therefore the outcomes are not necessarily due to taking varenicline, she noted.  

Moreover, Pagidipati added, "we don't know if the patients actually took the drug for 12 weeks or at all, only that they filled the prescription. This is important, because we know that most patients do not complete a full course as prescribed. If they are not actually taking the drug, then the events during the observation period are not necessarily due to varenicline. "

Further, it's not known whether these patients actually quit smoking or not, which could further affect their chance of have a cardiovascular event, she said.

The authors acknowledge these study limitations.

Nevertheless, Gershon said, "We hope that physicians will be able to incorporate this with 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."

The was funded by the government of Ontario, the Institute for Clinical Evaluative Sciences (ICES), and the Ontario Ministry of Health and Long-Term Care (MOHLTC). The authors had no relevant financial relationships.  

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