Background/Purpose: Recent studies have shown a reduction in mortality among patients treated with bisphosphonates. It has been suggested this may be the result of reduction in cardiovascular deaths. In addition, calcium therapy has been linked to cardiovascular risk. Bisphosphonates, calcium and Vitamin D are commonly used in rheumatic disorders such as rheumatoid arthritis and lupus for prevention and treatment of osteoporosis. As the risk of myocardial infarction is increased in rheumatoid arthritis and lupus patients, we evaluated a cohort of these rheumatic disease patients to assess the risk of osteoporosis treatment, including bisphosphonates, on myocardial infarction.
Method: We studied 155,750 semiannual observations from 23,228 rheumatic disease patients from 2002 through 2010 (93% rheumatoid arthritis, 7% lupus) to determine the effect of bisphosphonate therapy on the risk of myocardial infarction. We used longitudinal population averaged logistic models and Cox regression analyses adjusted for demographic, economic, and cardiovascular risk factors.
Result: Over the course of the study, 26.4% of patients used bisphosphonates (alendronate 16.3%, risedronate 6.8%, ibandronate 3.1%, other bisphosphonates <0.2%). Age, sex, education, smoking, diabetes, hypertension, prednisone, and the use of statins predicted myocardial infarction, statins because of confounding by indication. Patients using bisphosphonates had more severe rheumatoid arthritis and lupus, with reduced functional status and increased prednisone and opioid use, among other measures. Bisphosphonate use was protective for myocardial infarction, odds ratio 0.75 (95% CI 0.58, 0.98), as was calcium and vitamin D (OR 0.57 (95% CI 0.42, 0.77). When calcium/vitamin D and bisphosphonates were analyzed as a group, the 3-drug combination resulted in an OR of 0.38 (95% CI 0.22, 0.66). Calcium and vitamin D alone was also associated with protective effect (OR 0.61 (95% CI 0.43, 0.87)). We also evaluated the effect of bisphosphonate use separately in patients just beginning bisphosphonate therapy, considering observations on therapy compared with those off therapy (Figure 1). The hazard ratio for the 3-drug use was 0.26 (95% CI 0.14, 0.51) in newly beginning patients. Calcium and bisphosphonates without vitamin D was also a significant predictor.
Conclusion: Myocardial infarction was reduced among rheumatic disease patients using bisphosphonate therapy after adjustment for known cardiovascular risk factors and for risk of prescription. Concomitant vitamin D use is associated with a further reduction in myocardial infarction. The data are consistent with studies that have shown reduced mortality risk in bisphosphonate users, and suggest that a randomized clinical trial may be indicated.
Disclosure: F. Wolfe, None; M. B. Bolster, Novartis, Amgen, Eli Lilly, 8 ; C. Colon-Emeric, Novartis, Amgen, Smithklin Beecham; Research: Novartis, Wyeth , 5, Bisphosphonate Cardiovascular Effects, 9 ; C. M. O'Connor, Johnson and Johnson, 5, 9, Co-founder Cardiobis, 9, Methods for preventing or reducing secondary fractures after hip fracture”, Number 20050272707, 9 ; K. Michaud, None; K. W. Lyles, Novartis, Alliance for Better Bone Health, Amgen, 2, Novartis, Procter & Gamble, Merck, Amgen, Kirin Pharmaceutical, GTx, Lilly, GSK, Bone Medical Ltd., Wyeth, Osteologix, 5, Patent, 9 .