Bisphosphonates and cardiovascular risk in elderly patients with previous cardiovascular disease: a population-based nested case-control study in Italy

Background: In a globally aging population, chronic conditions with a high impact on healthcare costs and quality of life, such as osteoporosis and associated fractures, are a matter of concern. For osteoporosis, several drug treatments are available, but evidence on adverse cardiovascular and cerebrovascular (CCV) events, and in particular the risk of atrial fibrillation (AF), related to anti-osteoporotic drug use is inconclusive. The objective of this study was to evaluate the association between the use of bisphosphonates (BPs), strontium ranelate (SR), and other anti-osteoporosis drugs and the risk of AF and CCV events in a large cohort of patients affected by CCV diseases. Methods: Based on a cohort of patients aged 65 years and over, discharged from the hospitals of five large Italian areas after a CCV event between 2008 and 2011, two nested case-control studies were conducted. Cases were patients with a subsequent hospital admission for AF or CCV; four controls for each case were randomly selected and matched by age group, sex and follow-up time. A total of three exposure measures were tested: ever use, adherence and recency of use. In the conditional logistic regression models, patients not treated with any anti-osteoporotic medication were considered as the reference category. Results: The initial cohort accounted for 657,246 patients. Neither BPs nor SR use was associated with an increased risk of AF regardless of the adherence and recency of use. Overall BP and SR use was associated with a slightly increased risk of CCV; however, results reversed when considering higher adherence: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.71-0.92 for BPs and OR 0.71, 95% CI 0.52-0.97 for SR. Conclusions: BPs do not increase cardiovascular risk and can be prescribed to elderly patients for osteoporosis treatment. However, patients with pre-existing cerebrovascular/cardiovascular conditions should be carefully monitored.