Study demonstrates increased cardiovascular risk associated with varenicline

July 22, 2011

A recent study raises safety concerns associated with the use of varenicline among tobacco users. Use of the drug was associated with a 72% increased risk of serious adverse cardiovascular events and deserves further investigation, according to results of the study, which was published July 4 in the Canadian Medical Association Journal.

A recent study raises safety concerns associated with the use of varenicline among tobacco users. Use of the drug was associated with a 72% increased risk of serious adverse cardiovascular events and deserves further investigation, according to results of the study, which was published July 4 in the Canadian Medical Association Journal.

Investigators searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, Regulatory websites, and clinical trial registries in September 2010. An updated search was conducted in March 2011. Included in the study were 14 double-blind, randomized placebo-controlled trials of 8,216 participants with treatment duration ranging from 7 to 52 weeks that evaluated varenicline as the intervention drug versus a placebo among tobacco users and in which serious adverse cardiovascular events were reported.

The meta-analysis showed a significantly increased risk of serious adverse cardiovascular events associated with varenicline compared with placebo. Sensitivity analyses each showed results similar to the primary analysis.

“The robustness of the effect size to alternative statistical approaches or comparators in various sensitivity analyses suggests that this safety signal deserves further investigation,” the authors wrote. “Despite the limitations of our analysis, our findings
have potential regulatory and clinical implications,” the authors added.

At the time of the study’s publication, FDA released a safety announcement about varenicline (Chantix) stating that it may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease, and the safety information would be added to the Warnings and Precautions section of the physician labeling. In addition, the patient Medication Guide would be revised accordingly.

FDA’s decision was based on the review of a randomized clinical trial of 700 smokers with cardiovascular disease who were treated with Chantix or placebo. Although adverse events were generally infrequent and Chantix was effective at helping patients quit and abstain from smoking for as long as a year, certain events, including heart attack, were reported more frequently in patients treated with Chantix over placebo.

FDA advised healthcare practitioners deciding to prescribe the drug to smokers with cardiovascular disease to weigh the known benefits against its potential risks. The agency added that it is continuing to evaluate the cardiovascular safety of the drug and has required Pfizer, the drug’s manufacturer, to conduct a large, meta-analysis of randomized, placebo-controlled trials.