Women who take popular osteoporosis drug alendronate, known more commonly as Fosamax, are twice as likely to develop a common form of irregular heartbeat compared to those who have never taken it, a new study suggests.

Researchers analyzed data from more than 700 women who had been diagnosed with atrial fibrillation, or irregular heartbeat, in a three-year period and compared them to a control group of more than 900 randomly selected women.

They found a nearly two-fold increase in risk for developing atrial fibrillation among those women who had ever taken alendronate.

The findings were compiled by researchers from Group Health and the University of Washington by analyzing records of patients enrolled in Group Health, a Seattle-based non-profit health-care centre. The study was published Monday in the journal Archives of Internal Medicine.

Alendronate is part of a family of drugs known as bisphosphonates, which are widely used to protect against bone loss and prevent bone fracture in osteoporosis patients.

However, the researchers did not find a difference in risk among those who had taken Fosamax in the past versus current users.

"We do not conclude that the risk is higher for past use than current use. We conclude that the risk is higher for ever use than for never use, which was our original hypothesis," said lead study author Dr. Susan Heckbert, a professor of epidemiology and scientific investigator in the cardiovascular health research unit at the University of Washington.

Heckbert said that the next step would be for scientists to investigate the mechanism for how alendronate may influence the onset of atrial fibrillation.

Marlene Gauthier, manager of public affairs for Merck Frosst Canada, responded to the findings by saying that a clinical trial, rather than an observational study such as this one, is the best way to evaluate a drug's benefits and risks.

"While observational analyses are usually conducted in as rigorous a manner as possible, they are associated with inherent limitations, including factors that cannot be adequately controlled for and an ability to fully account for differences in risk factors between groups. This underscores why data from randomized, controlled clinical trials are considered to be the most reliable source of information about the efficacy and safety of medicines."

The statement continued: "We strongly recommend that if patients have concerns about Fosamax that they talk to their physician. Osteoporosis is a serious medical condition and requires appropriate treatment with physician oversight. Their physician is in the best position to understand the needs of the patient and explain the benefits and risks of any given therapy to the patient."

"This is an observational study. It is not as strong a design as a clinical trial," Heckbert acknowledged.

"But on the other hand, it does represent what's happening in actual clinical medicine."

Heckbert said her team knew of previous study findings that suggested a link between bisphosphonates and an increased risk for atrial fibrillation.

In fact, in the United States there are more than 400 cases pending against Merck in both state and federal court, in which people who have taken Fosamax claim that the drug has contributed to the development of osteonecrosis of the jaw. This happens when bone tissue dies after it loses its blood supply, and can occur after trauma to the bone, such as a dental procedure.

However, Heckbert warned that patients who take alendronate should not stop taking it due to her study's findings.

"If individuals are concerned they should speak with their physician or their health-care provider," Heckbert said.

"For patients who are at high risk of fracture, the benefits of alendronate or other bisphosphonates will generally outweigh the risk of atrial fibrillation."

Abstract:

Use of Alendronate and Risk of Incident Atrial Fibrillation in Women

Susan R. Heckbert, MD, PhD; Guo Li, MS; Steven R. Cummings, MD; Nicholas L. Smith, PhD; Bruce M. Psaty, MD, PhD.

Background: A recent publication from the HORIZON (Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly) trial in women with postmenopausal osteoporosis reported a higher risk of serious atrial fibrillation (AF) in zoledronic acid recipients than in placebo recipients. This adverse effect was unexpected and had not been recognized previously.

Methods: We studied alendronate sodium ever use in relation to the risk of incident AF in women in a clinical practice setting. This population-based case-control study was conducted at Group Health, an integrated health care delivery system in Washington State. We identified 719 women with confirmed incident AF between October 1, 2001, and December 31, 2004, and 966 female control subjects without AF, selected at random from the Group Health enrollment and frequency matched on age, presence or absence of treated hypertension, and calendar year.

Results: More AF case patients than controls had ever used alendronate (6.5% [n=47] vs 4.1% [n=40]; P=.03). Compared with never use of any bisphosphonate, ever use of alendronate was associated with a higher risk of incident AF (odds ratio, 1.86; 95% confidence interval, 1.09-3.15) after adjustment for the matching variables, a diagnosis of osteoporosis, and a history of cardiovascular disease. Based on the population-attributable fraction, we estimated that 3% of incident AF in this population might be explained by alendronate use.

Conclusion: Ever use of alendronate was associated with an increased risk of incident AF in clinical practice.