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Posts Tagged ‘Hazard ratio’


Reporter: Aviva Lev-Ari, PhD, RN

Amiodarone Linked to Cancer Risk in Men

SOURCE:

Su V, et al. “Amiodarone and the risk of cancer: a nationwide population-based study” Cancer 2013; DOI: 10.1002/cncr.27881.

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
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E. Kevin Heist, MD, PhD
MGH
Corrigan Minehan Heart Center

The risk of cancer was increased in men taking the antiarrhythmia drug amiodarone (Nexterone), 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.

Primary source: Cancer
Source reference:
Su V, et al. “Amiodarone and the risk of cancer: a nationwide population-based study” Cancer 2013; DOI: 10.1002/cncr.27881.

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease

Original Article

Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease

J.B. Olesen and Others

The prevalence of both atrial fibrillation and chronic kidney disease increases with age. The prevalence of atrial fibrillation is 2.3% among persons 40 years of age or older and 5.9% among those 65 years of age or older, and the prevalence of end-stage renal disease increases from approximately 3.5% among persons 45 to 64 years of age to nearly 6% among those 75 years of age or older. Many patients have both disorders, and the number of such patients is increasing, owing in part to the aging population and the improved survival in both diseases.

Clinical Pearls

  What is the effect of chronic kidney disease on the risk of stroke?

The U.S.-based Renal Data System has reported that chronic kidney disease increases the risk of stroke by a factor of 3.7, and end-stage renal disease (i.e., disease requiring renal-replacement therapy) increases the risk by a factor of 5.8. Atrial fibrillation increases the risk of stroke by a factor of 5, and chronic kidney disease increases the risk of stroke among patients without atrial fibrillation.

  What is a CHA2DS2-VASc score?

This study evaluated the risk of stroke or systemic thromboembolism, with adjustment for CHA2DS2-VASc risk factors. The CHA2DS2-VASc score extends the CHADS2 algorithm to include additional nonmajor risk factors for stroke, including vascular disease (V), age between 65 to 74 years (A), and female gender (sex category or Sc).

Morning Report Questions

Q. What were the results of this study of patients with atrial fibrillation and chronic kidney disease with respect to risk of stroke or systemic embolism? 

A. This study demonstrated that warfarin treatment was associated with a significantly decreased risk of stroke or systemic thromboembolism overall and among patients requiring renal-replacement therapy, and with a nonsignificantly decreased risk among patients with non–end-stage chronic kidney disease. In an analysis that compared all patients who had any renal disease with those who had no renal disease, warfarin decreased the risk of stroke or systemic thromboembolism (hazard ratio, 0.76; 95% CI, 0.64 to 0.91; P=0.003), as did warfarin plus aspirin (hazard ratio, 0.74; 95% CI, 0.56 to 0.98; P=0.04). Aspirin alone was associated with an increased risk of stroke or systemic thromboembolism overall and among patients who had any renal disease, as compared with those who had no renal disease (hazard ratio, 1.17; 95% CI, 1.01 to 1.35; P=0.04).

Table 3. Hazard Ratios for Stroke or Systemic Thromboembolism.

Q. How did the risk of bleeding differ among patients with and without kidney disease? 

A. The risk of bleeding was higher among patients with non–end-stage chronic kidney disease and among patients requiring renal-replacement therapy as compared to patients without renal disease, and treatment with warfarin, aspirin, or both incrementally increased this risk. Among all patients who had any renal disease, as compared with those who had no renal disease, there was an increased risk of bleeding with warfarin (hazard ratio, 1.33; 95% CI, 1.16 to 1.53; P<0.001), aspirin (hazard ratio, 1.17; 95% CI, 1.02 to 1.34; P=0.03), and warfarin plus aspirin (hazard ratio, 1.61; 95% CI, 1.32 to 1.96; P<0.001). Among patients with non–end-stage chronic kidney disease, the risk of bleeding increased with a higher dose of loop diuretics. The risk of bleeding was highest among patients with chronic glomerulonephritis and lowest among those with chronic tubulointerstitial nephropathy.

Table 4. Hazard Ratios for Bleeding.

 Original article

Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease

Jonas Bjerring Olesen, M.D., Gregory Y.H. Lip, M.D., Anne-Lise Kamper, M.D., D.M.Sc., Kristine Hommel, M.D., Lars Køber, M.D., D.M.Sc., Deirdre A. Lane, Ph.D., Jesper Lindhardsen, M.D., Gunnar Hilmar Gislason, M.D., Ph.D., and Christian Torp-Pedersen, M.D., D.M.Sc.

N Engl J Med 2012; 367:625-635  August 16, 2012

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