FDA Safety Review Finds Small, Nonsignificant Increased Risk With Chantix (Varenicline) Reply

The FDA today updated its safety review of the smoking cessation drug varenicline (Chantix, Pfizer). A large meta-analysis, which the FDA had required Pfizer to perform, found a higher rate of major adverse cardiovascular events (MACE) in patients taking varenicline than in patients taking placebo. However, the increase in risk was very small and did not achieve statistical significance. The FDA concluded that “it is uncertain whether the excess risk for the Chantix group was due to the drug or due to chance.”

The FDA said the results of the meta-analysis are consistent with findings of an earlier trial described in a previous FDA communication. The new meta-analysis utilizes data from 7,002 patients who were randomized to placebo or varenicline in one of 15 double-blind trials.

The FDA reported a low MACE rate for both groups. Although varenicline-treated patients had nearly double the risk of an event as the placebo-treated patients, there was a wide range in the confidence interval. The FDA noted that cardiovascular mortality and all-cause mortality was slightly lower in the varenicline-treated group, though the difference was of course not statistically significant.

Here’s the data from the meta-analysis:

MACE: varenicline 0.31% [13/4190] vs. placebo 0.21% [6/2812]

  • Adjusted hazard ratio: 1.95 (CI: 0.79-4.82)

Cardiovascular mortality: varenicline 0.05% [2/4190] vs. placebo 0.07% [2/2812], p=ns

All-cause mortality: varenicline 0.14% [6/4190] vs. placebo 0.25% [7/2812], p=ns

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No Surprise: Smoking and Sudden Cardiac Death Closely Tied 3

Although cigarette smoking has long been linked to cardiovascular (CV) disease and sudden cardiac death (SCD),  the precise contribution of smoking, and the effect of smoking discontinuation, on SCD has not been clear. Now a new report from the Nurses’ Health Study published in Circulation: Arrhythmia & Electrophysiology provides new clarity about the relationship between smoking and SCD.

“Cigarette smoking is a known risk factor for sudden cardiac death, but until now, we didn’t know how the quantity and duration of smoking affected the risk among apparently healthy women, nor did we have long-term follow-up,” said lead investigator Roopinder Sandhu, in an AHA press release.

Dr. Sandhu and colleagues analyzed data from more than 100,000 women without known CV disease or cancer.  During 30 years of followup there were 351 incident SCDs. Compared to women who never smoked, the risk of SCD was significantly elevated in current smokers (relative risk 2.44) and former smokers (RR 1.40).

The number of cigarettes smoked each day was correlated with the increase in SCD risk, but even women who smoked only 1-14 cigarettes per day had a significant 1.84-fold increase in risk. Women who smoked more than 25 cigarettes a day had a 3.3-fold increase in risk. Smoking duration was also significant, resulting in an 8% increase in SCD risk for every 5 years of smoking.

Women who quit smoking reduced their SCD risk. After 15 years the reduction in risk achieved statistical significance, and by 20 years the risk was similar to women who had never smoked.

In an exploratory analysis, women smokers with coronary heart disease (CHD) had a much higher incidence of SCD than women without CHD. Women with CHD who quit smoking did not enjoy the same immediate reduction in SCD risk as observed in women without CHD.

“Sudden cardiac death is often the first sign of heart disease among women, so lifestyle changes that reduce that risk are particularly important,” said Dr. Sandhu. “Our study shows that cigarette smoking is an important modifiable risk factor for sudden cardiac death among all women. Quitting smoking before heart disease develops is critical.”
Click here to read the AHA press release…

The Research Agrees: Smoking Is Really Bad For You Reply

Four new studies offer powerful evidence of the dangers of smoking and the health benefits of quitting or not being exposed to secondhand smoke.

Smoking in the UK– Between 1996 amd 2001 the Million Women Study started following more than one million women aged 50 to 65 years of age. In  a report published in the Lancet, trial investigators, including renowned epidemiologist Richard Peto, found that 12-year mortality was significantly higher in women with a history of smoking compared to women who never smoked (rate ratio 2.76, CI 2.71-2.81). Smokers, the authors calculated, lose 10 years of life. The good news is that stopping smoking before the age of 40 reduces the excess mortality by 90%.

Smoking in Japan– The Life Span Study, published in BMJ, was started in 1950 and has followed more than 65,000 men and women in Hiroshima and Nagasaki, Japan. The results were consistent with the Million Women Study in the UK: the rate ratio for mortality was more than doubled for smokers compared to nonsmokers both for men (2.21, CI 1.97-2.48) and for women (2.61, CI 1.98-3.44). The investigators also reported that stopping smoking before age 35 eliminated almost all of the risk associated with smoking.

Smoke-free legislation meta-analysis– Smoking is not just a personal decision that has individual health effects. A new meta-analysis published in Circulation found that smoke-free legislation results in immediate reductions in hospital admissions or deaths for coronary events (RR .848, CI .816-.881), other heart disease (RR .610, CI .440-.847), cerebrovascular accidents (RR .840, CI .753-.936) and respiratory disease (RR .760, CI .682-.846). The authors, Crystal Tan and Stanton Glatz, also report that the biggest reductions in events were associated with the most stringent smoke-free laws.

Smoke-free legislation in Minnesota– Here’s one more study to lend support to the above meta-analysis. In a paper published in Archives of Internal Medicine Richard Hurt and colleagues analyzed data before and after the implementation of a smoke-free law in Olmsted County, Minnesota and found a significant 33% reduction in the incidence of MI from 150.8 to 100.7 per 100000 people and a trend in the reduction of sudden cardiac death by 17% from 109.1 to 92.0 per 100,000 people. In an accompanying commentary, Sara Kalkhoran and Pamela Ling write that as “the evidence base documenting the positive health outcomes” of smoke-free legislation grows, “we should prioritize the enforcement of smoke-free policies, eliminating loopholes in existing policies as well as encouraging expansion of smoke-free policies to include multiunit housing, motor vehicles, casinos, and outdoor locations. Exposure to SHS should not be a condition of employment, and all workers, including those of lower income and those in the service and hospitality industries, should have equal protection from SHS exposure.”
Click here to read the press releases from the Lancet, BMJ, Circulation, and Archives…