ORLANDO — Further evidence that bisphosphonates do not really increase the risk of atrial fibrillation has come from an observational study involving more than 47,000 patients.
“We were unable to find an association between bisphosphonate therapy and atrial fibrillation. 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,” Dr. John D. Day reported at the annual meeting of the American College of Cardiology.
The study population comprised 37,485 enrollees in a Rocky Mountain health plan followed for an average of 4.6 years and 9,623 consecutive patients in a coronary angiography database with an average follow-up of 4 years.
The 7,489 health plan enrollees on bisphosphonate therapy for osteoporosis and fracture prevention had a 37% baseline prevalence of hyperlipidemia, significantly greater than the 30% rate among plan members not on a bisphosphonate. The bisphosphonate users were older, too. Yet their rates of new-onset atrial fibrillation, MI, and all-cause mortality during follow-up were no different than nonusers', according to Dr. Day of Intermountain Medical Center, Murray, Utah.
In the coronary angiography cohort, the patients on bisphosphonates were significantly older than were bisphosphonate nonusers, were more likely to be hypertensive by a margin of 56% to 45%, and had a 4.1% prevalence of heart failure compared with 0.7% in patients not on a bisphosphonate. A prior MI was present at baseline in 12.2% of bisphosphonate users and 4.8% of nonusers.
The all-cause mortality rate was 32.7% in bisphosphonate users in the angiography cohort and 18.8% in nonusers. Yet the rates of new-onset atrial fibrillation in the two groups were essentially the same: 10.2% among bisphosphonate users, 10.1% in nonusers.
In November 2008, the Food and Drug Administration reported that based on its review of the data from clinical trials involving nearly 40,000 patients treated with alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), zoledronic acid (Zometa), or placebo, there is “no clear association” between the use of drugs in this class and the rate of serious or nonserious atrial fibrillation. The FDA report concluded that physicians “should not alter their prescribing patterns for bisphosphonates.”
However, because of discordance among some of the studies, agency officials left the door open to possible future epidemiologic studies addressing the issue, prompting Dr. Day and coinvestigators to look at their patients' experience.
The FDA review was prompted by published reports of an apparent increase in serious atrial fibrillation events with zoledronic acid in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON) and with alendronate in the Fracture Intervention Trial (FIT) (N. Engl. J. Med. 2007;356:1809–22, 1895–6).
Dr. Day reported having no financial conflicts of interest relating to the study.