Relation of bisphosphonate therapies and risk of developing atrial fibrillation

Bisphosphonates comprise the most common treatment for patients with osteoporosis and fracture risk. Large randomized trials have shown that these therapies may increase the risk of atrial fibrillation (AF). Controversy over the arrhythmia risk prompted the Federal Drug Administration to recently pursue an ongoing safety review to determine the cardiac risk across the entire drug class. Study patients came from 2 large prospective databases (ongoing registry of consecutive patients who underwent coronary angiography and the Intermountain Healthcare health plans database). Medical details regarding bisphosphonate use and cardiovascular risk factors were abstracted from the records. End points included AF, myocardial infarction, and death. In the angiographic database (n = 9,623), patients treated with bisphosphonates were older and more likely to have hypertension, a previous myocardial infarction, heart failure, and osteoporosis. Over 1,481 +/- 1,024 days we found no increased risk of AF in the drug-treated group (hazard ratio 0.90, 95% confidence interval 0.48 to 1.68, p = 0.74). In the Intermountain Healthcare health plans database (n = 37,485), patients treated with bisphosphonates were older and were more likely to have hyperlipidemia and osteoporosis. Over 1,667.5 +/- 557.0 days, there was no increased risk of AF (hazard ratio 0.82, 95% confidence interval 0.66 to 1.01, p = 0.63). In the 2 databases there was no statistical difference in long-term rates of myocardial infarction or mortality. In conclusion, in a long-term study of >47,000 patients, we were unable to find an association between bisphosphonate therapy and AF. However, patients who received bisphosphonates were older and had more cardiovascular disease that we suspect accounts for the increased arrhythmia risk reported in other trials.