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Friday, April 12, 2013

Study Links Amiodarone to Cancer Risk in Men


By Nancy Walsh, Staff Writer, MedPage Today
Published: April 08, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
The risk of cancer was increased in men taking the antiarrhythmia drug amiodarone, particularly in those with extensive exposure to the drug, a retrospective study found.
Among men taking amiodarone, the risk for any cancer rose by almost 20% compared with the general population, with a standardized incidence ratio of 1.18 (95% CI 1.02 to 1.36, P=0.022), according to Chia-Jen Liu, MD, of National Yang-Ming University Hospital in Yilan, Taiwan, and colleagues.
And for men whose cumulative defined daily doses in a year exceeded 180, the risk was 46% higher (SIR 1.46, 95% CI 1.11 to 1.89,P=0.008), the researchers reported online inCancer.
Amiodarone has been associated with a number of potentially serious adverse events, including thyroid dysfunction, pulmonary fibrosis, and skin and thyroid malignancies, and a meta-analysis suggested a possible cancer link.
To examine the potential for an association with cancer, Liu and colleagues analyzed data from the Taiwanese National Health Insurance Research Database, identifying 6,418 patients who received amiodarone between 1997 and 2008.
More than half were men, the median age was 70, and median follow-up was 2.57 years.
Comorbidities were common, including hypertension (76%), heart failure (47%), chronic obstructive pulmonary disease (44%), and diabetes (39%).
During observation of almost 22,000 person-years, 280 cancers were identified.
Patients who had received amiodarone had a borderline increased risk of about 10% for all cancers (SIR 1.12, 95% CI 0.99 to 1.26, P=0.067), with a lag time of about 2 years.
Women did not appear to be at increased risk (SIR 99, 95% CI 0.79 to 1.23).
A possible explanation for the gender difference was that women clear the drug more quickly than men. Amiodarone has a half-life of almost 2 months and can accumulate in tissues, the researchers explained.
Among men, an elevated risk was seen for those ages 20 to 60 (SIR 1.67, 95% CI 1.07 to 2.48,P=0.025) and those over 80 (SIR 1.41, 95% CI 1.07 to 1.83, P=0.016).
Multivariate analysis identified these factors as being associated with increased risk:
  • Age: hazard ratio 1.04 (95% CI 1.03 to 1.06, P<0.001)
  • Male: HR 1.90 (95% CI 1.38 to 2.62, P<0.001)
  • Cirrhosis: HR 3.70 (95% CI 2.10 to 6.52, P<0.001)
  • Socioeconomic status: HR 0.63 (95% CI 0.45 to 0.87, P=0.006)
  • Cumulative daily doses: HR 1.001 for each additional dose (95% CI 1 to 1.002, P=0.022)
The researchers also analyzed risks when cumulative daily doses were stratified into tertiles. They found that patients in the intermediate and highest levels of cumulative doses had adjusted HRs of 1.70 (95% CI 1.02 to 2.84, P=0.042) and 1.98 (95% CI 1.22 to 3.22, P=0.006), respectively.
But they didn't find any differences for specific types of cancer, including lung, thyroid, and skin.
That was a surprising finding, according to E. Kevin Heist, MD, PhD, of Massachusetts General Hospital Corrigan Minehan Heart Center in Boston, who was not involved in the study.
"Most carcinogens tend to increase risk of individual cancers," Heist told MedPage Today.
"Even things like radiation that affect all cells of the body tend to increase individual cancer risks. So it does make one wonder why this is different than other known carcinogens, and whether in fact this is a real finding," Heist said.
The researchers also pointed out that the numbers of individual cancers were small and the follow-up of 2.57 years may not have been long enough to detect actual differences.
Other limitations of the study included its cohort design, the unavailability of information on potential risk factors such as smoking, family history, and exposure to environmental toxins.
"Although extensive screenings for occult cancers in patients currently undergoing treatment with amiodarone appears to be impractical, we suggest that cancer events should be routinely reported in future amiodarone trials," the researchers concluded.
For the time being, patients who need amiodarone should still receive it, but clinicians should exercise caution, Heist advised.
"I think the big messages are keep using it when you need to use it, but make sure you need it and make sure a safer alternative antiarrhythmic drug is not an option or has not been tried," he said.
The study was supported by Taipei Veterans General Hospital.
The authors reported no financial conflicts.
From the American Heart Association:

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