Cory B Pittman1, Lisa A Davis2, Angelique L Zeringue3, Liron Caplan4, Kent R Wehmeier5, Jeffrey F Scherrer6, Hong Xian7, Francesca E Cunningham8, Jay R McDonald3, Alexis Arnold9, Seth A Eisen10. 1. Mercy Arthritis and Osteoporosis Center, Urbandale, IA. Electronic address: cpittman@mercydesmoines.org. 2. Denver Health and Hospital Authority, Denver, CO; Denver Veterans Affairs Medical Center, Denver, CO; University of Colorado School of Medicine, Aurora, CO. 3. Department of Medicine, St. Louis Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, MO. 4. Denver Veterans Affairs Medical Center, Denver, CO; University of Colorado School of Medicine, Aurora, CO. 5. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine-Jacksonville, St. Louis, MO. 6. Department of Psychiatry, St. Louis Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, MO. 7. Department of Biostatistics, St. Louis University College for Public Health & Social Justice, St. Louis, MO. 8. Veterans Affairs Pharmacy Benefits Management, Hines, IL. 9. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine-Jacksonville, St. Louis, MO; St. Olaf College, Northfield, MN. 10. Veterans Affairs Health Service Research and Development, Washington, DC.
Abstract
OBJECTIVE: To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. RESULTS: After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. CONCLUSION: Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.
OBJECTIVE: To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. RESULTS: After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. CONCLUSION: Our observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.
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