Bisphosphonates and mortality in women with CKD and the presence or absence of cardiovascular disease

Background and objectives A modest protective association between bisphosphonate prescription and mortality among women with CKD but without clinically manifest cardiovascular disease has been shown. Whether a prior cardiovascular event (myocardial infarction, stroke, or heart failure) modifies this association is unknown. Design, setting, participants, & measurements A cohort of adult women with stages 3 and 4 CKD receiving primary care in a rural integrated health care system during the period 2004-2011 without history of advanced malignancy or organ transplantation (n=6756, median age=74 years, median follow-up=4.3 years) was retrospectively assembled. The primary analysis compared those patients prescribed bisphosphonates (both prevalent and incident use during follow-up) with those patients not prescribed. Additional approaches were taken to account for survival and indication biases. The primary outcome was time to death by Cox multivariable regression. Results In the primary analysis, compared with women not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was history of cardiovascular event (P for interaction=0.004). In the additional approaches, associations between bisphosphonate prescription and mortality among those patients with a prior cardiovascular history varied: hazard ratios (95% confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94 (0.66 to 1.34). Interaction by prior cardiovascular event history varied across these three approaches (P=0.07, P=0.22, and P=0.05). Conclusion In this study of women with CKD, the association between bisphosphonate treatment and mortality risk was inconclusive across a series of analyses designed to account for various types of selection and indication bias.