The FDA Reports No Association between Bisphosphonate Use and Atrial Fibrillation

Armand Rossetti

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Yesterday, the FDA released an update about the agency’s safety data review, regarding the increased risk of atrial fibrillation in patients treated with seven available bisphosphonate compounds, including Fosamax, Boniva and Reclast.

Doctors prescribe bisphosphonate based compounds in order to increase bone mass and to reduce risk of fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer.

In its most recent bisphosphonate update, the FDA reported that it had reviewed data on 19,687 bisphosphonate treated patients and 18,358 placebo-treated patients followed for 6 months to three years. Although the FDA did not provide a breakdown by brand name, and did not indicate the number of studies that comprised the review, the FDA did state that with most studies, atrial fibrillation was rare. Accordingly, most studies contained two or fewer events, and there was no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation.

The FDA’s conclusion concerning atrial fibrillation comports with a Danish study entitled, “Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study,” which appeared in the April 12, 2008 edition of the British Medical Journal. The study's authors carried out a population based case-control study using databases from four Danish counties having a combined population of 1.7 million, and included a total of 68,054 population controls and 13,586 patients with atrial fibrillation, each having a complete hospital and prescription history. The Danish investigators came to the following conclusion:

“What is already known on this topic:

• Bisphosphonates are widely used in the treatment of osteoporosis; and

• Data from clinical trials have reported that bisphosphonates may increase the risk of atrial fibrillation but data on their potential toxicity are scanty and conflicting.

What this study adds:

• Patients with atrial fibrillation and flutter had a similar frequency of use of etidronate and alendronate as population controls; and

• No evidence was found that use of bisphosphonates increases the risk of atrial fibrillation and flutter.”

However, the FDA did not comment in its November 12^th update, concerning the following connections between bisphosphonates and certain conditions:

• Osteonecrosis of the jaw (Oral and IV administration);
• Esophageal problems such as upper gastrointestinal adverse events (oral administration); and
• Acute renal failure (IV administration of etidronate).

The FDA update might have also included a reminder that many of the newest bisphosphonate formulations offer patients a choice in both dosing frequency and method of administration (either oral or intravenous).

However, it is comforting to know that the FDA has performed a thorough investigation, concerning bisphosphonate and its alleged connection with atrial fibrillation. Therefore, the FDA should be congratulated for its interest and perserverance.