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IV bisphosphonates associated with increased risk for stroke, atrial fibrillation in older patients with cancer
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Patients older than 65 years with cancer who were treated with intravenous bisphosphonates had an 8% greater risk for atrial fibrillation or all supraventricular tachycardia after 6 years, and a 4% greater risk for stroke, according to the results of a retrospective study.
Researchers reviewed records collected in the SEER database on 6,857 patients who were treated with bisphosphonates from Jan. 1, 1986 to Dec. 31, 2002, and compared the results with 19,714 patients who were not assigned to bisphosphonates. All participants were aged at least 65 years at diagnosis.
The study did not differentiate between pamidronate and zoledronic acid.
After 3 years, 18% of bisphosphonate users had been diagnosed with atrial fibrillation compared with 12.7% of the control group, which translates into a difference in absolute risk of 5.3% (95% CI, 3.1%-7.7%). The difference increased to 8% at 6 years.
For all supraventricular tachycardia, 28% of the bisphosphonate group had been diagnosed at 3 years compared with 20.4% for nonusers, for an absolute risk difference of 7.6% (95% CI, 4.9%-10.4%). Six-year absolute risk was 7.8%.
At 3 years, 5.5% of the bisphosphonate group had been hospitalized for stroke compared with 4.1% of nonusers, for a difference in absolute risk of 1.5% (95% CI, 0.1%-2.0%). The difference more than doubled to 4% at 6 years.
After adjusting for potential confounding factors such as diabetes, hypertension and obesity, researchers found that there remained an elevated risk for atrial fibrillation (HR=1.30; 95% CI, 1.18-1.43), all supraventricular tachycardia (HR=1.28; 95% CI, 1.19-1.38) and stroke (HR=1.30; 95% CI, 1.09-1.54) for patients assigned to bisphosphonates.
Writing in an accompanying editorial, Julie R. Gralow, MD, professor of medical oncology with the University of Washington School of Medicine in Seattle, said it is still an open question whether bisphosphonates increase rates of cardiac arrhythmia and stroke, but results from this study and others provide enough evidence to support prospective trials looking into the issue.
“A causal relationship between atrial fibrillation, stroke and bisphosphonates is unproven by existing evidence. Until further data are available, providers should take all potential adverse effects into account,” she wrote. “All efforts should be made to prevent, recognize, and effectively manage complications of these drugs, including repleting calcium and vitamin D, treating acute phase reaction symptoms and bone pain, and monitoring renal function with the intravenous agents. Before prescribing any bisphosphonates, risks and benefits must be carefully weighed by physicians and well-informed patients.”
For more information:
- Wilkinson GS. J Clin Oncol. 2010;doi:10.1200/JCO.2010.28.7524.