Unringing the Bell of Alarm on Varenicline

When the Surgeon General released its 31st report on Preventing Tobacco Use Among Youth and Young Adults: A Report of the Surgeon General earlier this year, media outlets picked up on the slowing of declines in youth cigarette smoking and the stalling of declines in smokeless tobacco use. The report estimated that more than 3 million high school students – 80% of high school smokers – will continue to smoke into adulthood.

Tobacco use prevention is indeed critical for the health of our youth and practicing clinicians need to be ready to treat these newly minted tobacco users when they walk into our offices. To do this, we need accurate information on the efficacy and safety of pharmacotherapy for the treatment of tobacco dependence.

Varenicline (Chantix) is arguably the most effective medication for the treatment of tobacco dependence. But as with many new medications, metaanalyses of published clinical data are conducted as both formal and informal components of postmarketing surveillance. Some findings regarding varenicline have struck the bell of alarm. 

Dr. Sonal Singh of Johns Hopkins University School of Medicine, Baltimore, and colleagues published a metaanalysis suggesting that varenicline may increase the risk for cardiovascular events (CMAJ 2011;183:1359-66). This study was controversial primarily because it included events beyond the period of drug exposure and excluded trials with no events. The findings, however, were the basis for including information about cardiovascular risk on the Chantix drug label.

New data published last week by Judith J. Prochaska, Ph.D., of the University of California, San Francisco, and a colleague (BMJ 2012; 344 doi: 10.1136/bmj.e2856) suggest that varenicline does not increase the risk for cardiovascular events. This metaanalysis analyzed serious cardiovascular events occurring during treatment or within 30 days of discontinuation. Twenty-two randomized, controlled clinical trials were included. No significant difference in risk for cardiovascular events was observed between the varenicline and placebo groups.

The critical difference between the two metaanalyses is that Dr. Prochaska’s analysis focused on events during drug exposure. On balance, it’s only reasonable to expect that the safety of a drug administered for a short period of time be evaluated in the time frame that the drug is given. This is especially true for a drug that is given to a population that is at notably high risk for the disease of interest (i.e., cardiovascular disease event risk in smokers).

Smoking is the most important risk factor for cardiovascular disease and varenicline is the most effective medication for the treatment of tobacco dependence. Perhaps the real risk is that patients who would benefit the most from this medication may not receive it because it’s hard to unring the bell of alarm.

Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He is an investigator on clinical trials investigating the safety of varenicline. The opinions expressed are solely those of the author. Contact him at ebbert.jon@mayo.edu.

When the Surgeon General released its 31st report on Preventing Tobacco Use Among Youth and Young Adults: A Report of the Surgeon General earlier this year, media outlets picked up on the slowing of declines in youth cigarette smoking and the stalling of declines in smokeless tobacco use. The report estimated that more than 3 million high school students – 80% of high school smokers – will continue to smoke into adulthood.

Tobacco use prevention is indeed critical for the health of our youth and practicing clinicians need to be ready to treat these newly minted tobacco users when they walk into our offices. To do this, we need accurate information on the efficacy and safety of pharmacotherapy for the treatment of tobacco dependence.

Varenicline (Chantix) is arguably the most effective medication for the treatment of tobacco dependence. But as with many new medications, metaanalyses of published clinical data are conducted as both formal and informal components of postmarketing surveillance. Some findings regarding varenicline have struck the bell of alarm. 

Dr. Sonal Singh of Johns Hopkins University School of Medicine, Baltimore, and colleagues published a metaanalysis suggesting that varenicline may increase the risk for cardiovascular events (CMAJ 2011;183:1359-66). This study was controversial primarily because it included events beyond the period of drug exposure and excluded trials with no events. The findings, however, were the basis for including information about cardiovascular risk on the Chantix drug label.

New data published last week by Judith J. Prochaska, Ph.D., of the University of California, San Francisco, and a colleague (BMJ 2012; 344 doi: 10.1136/bmj.e2856) suggest that varenicline does not increase the risk for cardiovascular events. This metaanalysis analyzed serious cardiovascular events occurring during treatment or within 30 days of discontinuation. Twenty-two randomized, controlled clinical trials were included. No significant difference in risk for cardiovascular events was observed between the varenicline and placebo groups.

The critical difference between the two metaanalyses is that Dr. Prochaska’s analysis focused on events during drug exposure. On balance, it’s only reasonable to expect that the safety of a drug administered for a short period of time be evaluated in the time frame that the drug is given. This is especially true for a drug that is given to a population that is at notably high risk for the disease of interest (i.e., cardiovascular disease event risk in smokers).

Smoking is the most important risk factor for cardiovascular disease and varenicline is the most effective medication for the treatment of tobacco dependence. Perhaps the real risk is that patients who would benefit the most from this medication may not receive it because it’s hard to unring the bell of alarm.

Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He is an investigator on clinical trials investigating the safety of varenicline. The opinions expressed are solely those of the author. Contact him at ebbert.jon@mayo.edu.

When the Surgeon General released its 31st report on Preventing Tobacco Use Among Youth and Young Adults: A Report of the Surgeon General earlier this year, media outlets picked up on the slowing of declines in youth cigarette smoking and the stalling of declines in smokeless tobacco use. The report estimated that more than 3 million high school students – 80% of high school smokers – will continue to smoke into adulthood.

Tobacco use prevention is indeed critical for the health of our youth and practicing clinicians need to be ready to treat these newly minted tobacco users when they walk into our offices. To do this, we need accurate information on the efficacy and safety of pharmacotherapy for the treatment of tobacco dependence.

Varenicline (Chantix) is arguably the most effective medication for the treatment of tobacco dependence. But as with many new medications, metaanalyses of published clinical data are conducted as both formal and informal components of postmarketing surveillance. Some findings regarding varenicline have struck the bell of alarm. 

Dr. Sonal Singh of Johns Hopkins University School of Medicine, Baltimore, and colleagues published a metaanalysis suggesting that varenicline may increase the risk for cardiovascular events (CMAJ 2011;183:1359-66). This study was controversial primarily because it included events beyond the period of drug exposure and excluded trials with no events. The findings, however, were the basis for including information about cardiovascular risk on the Chantix drug label.

New data published last week by Judith J. Prochaska, Ph.D., of the University of California, San Francisco, and a colleague (BMJ 2012; 344 doi: 10.1136/bmj.e2856) suggest that varenicline does not increase the risk for cardiovascular events. This metaanalysis analyzed serious cardiovascular events occurring during treatment or within 30 days of discontinuation. Twenty-two randomized, controlled clinical trials were included. No significant difference in risk for cardiovascular events was observed between the varenicline and placebo groups.

The critical difference between the two metaanalyses is that Dr. Prochaska’s analysis focused on events during drug exposure. On balance, it’s only reasonable to expect that the safety of a drug administered for a short period of time be evaluated in the time frame that the drug is given. This is especially true for a drug that is given to a population that is at notably high risk for the disease of interest (i.e., cardiovascular disease event risk in smokers).

Smoking is the most important risk factor for cardiovascular disease and varenicline is the most effective medication for the treatment of tobacco dependence. Perhaps the real risk is that patients who would benefit the most from this medication may not receive it because it’s hard to unring the bell of alarm.

Jon O. Ebbert, M.D., is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He is an investigator on clinical trials investigating the safety of varenicline. The opinions expressed are solely those of the author. Contact him at ebbert.jon@mayo.edu.