Regulatory Focus™ > News Articles > Smoking Cessation Drug Chantix May Increase Cardiovascular Adverse Events, FDA Says

Smoking Cessation Drug Chantix May Increase Cardiovascular Adverse Events, FDA Says

Posted 13 December 2012 | By

The US Food and Drug Administration (FDA) has published a new safety review of the smoking cessation drug Chantix (varenicline), saying the manufacturer's meta-analysis shows a higher incidence of "major adverse cardiovascular events" (MACE) in Chantix users, but that the risks were not statistically significant.

The uncertainty of the results present challenges for the drug's manufacturer and sponsor, Pfizer. FDA noted the results were unclear whether the increased risk of adverse cardiovascular events was caused by the drug or by random chance. The meta-analysis pooled 4,190 users of Chantix and 2,812 patients who were given placebos. Users of Chantix experienced 13 (0.31%) MACE while only 6 (0.21%) of placebo users experience the same events.

"Although these findings were not statistically significant, they were consistent," FDA explained. "Because the number of adverse cardiovascular events was small overall, the power for finding a statistically significant difference in a signal of this magnitude is low."

Such risks were not unknown to either Pfizer or FDA before its 12 December announcement. The drug's approved safety labeling notes that patients should alert their doctors to any history of heart or blood vessel problems before starting Chantix, and that patients should alert their doctors to any worsening cardiovascular conditions. The risk of heart attack is also mentioned on the safety label. The cardiovascular language was added to the drug's labeling in June 2011 after the interim results from a 700-person clinical trial were made available to regulators. That study also showed a slight (1.1%) increase in heart attacks, need for coronary revascularization (1.4%) and peripheral vascular disease (0.5%). That study was statistically significant (p<0.0001), FDA wrote.

In a statement aimed at medical professionals and patients, FDA urged caution and for health care professionals to "weight the risks of Chantix against the benefits of its use." FDA was quick to note that the benefits of quitting smoking are "immediate and substantial," and did not make any note that the agency was re-evaluating its approval of the drug.

The drug already comes packaged with a Medication Guide as a result of its risks, which include the potential for "changes in behavior, hostility, agitation, depressed mood, suicidal thoughts or actions," among numerous other physical and psychological risks to patient safety.

But if the study showed some cause for alarm-albeit statistically insignificant cause-it may have also given it a boost in other areas. All-cause mortality among patients taking Chantix was lower (0.14%) than in patients taking a placebo (0.25%), as was cardiovascular mortality (0.05% versus  0.07%). These findings were also not statistically significant, FDA said.

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