Bisphosphonate Therapy, Death, and Cardiovascular Events Among Female Patients With CKD: A Retrospective Cohort Study

Background Accelerated vascular calcification contributes to cardiovascular disease burden in patients with chronic kidney disease (CKD). We hypothesized that bisphosphonate therapy would reduce the risk of mortality and cardiovascular events in this population. Study Design Retrospective cohort study. Setting & Participants Adult women with stage 3 or 4 CKD receiving primary care in a large rural integrated health care system in 2004-2010. Exposure Time-dependent exposure status based on outpatient prescription for any medication within the bisphosphonate class, obtained from electronic health records. Outcomes Time to death and first cardiovascular event (composite of myocardial infarction, heart failure, or stroke). Results Data from 9,604 eligible female patients with CKD were analyzed; 3,234 were treated with bisphosphonate therapy. During a median follow-up of 3.9 (25th-75th percentile, 2.3-5.4) years, there were 286 versus 881 deaths and 206 versus 571 cardiovascular events (treated vs not-treated groups, respectively). In a multivariate Cox proportional hazard model, the adjusted HR for death (treated vs not treated) was 0.78 (95% CI, 0.67-0.91; P = 0.003). In Cox modeling adjusted for similar baseline covariates, treatment with bisphosphonates was not associated with a lower risk of the composite cardiovascular outcome (adjusted HR, 1.14; 95% CI, 0.94-1.39; P = 0.2). Limitations Residual confounding by unidentified factors, exclusion of male patients, and lack of information about longitudinal drug adherence. Conclusions For female patients with CKD, treatment with bisphosphonates is associated with a lower risk of death, but not cardiovascular events. Confirmatory studies and investigations of potential causal mechanisms are warranted.