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Bisphosphonate therapy, death, and cardiovascular events among female patients with CKD: a retrospective cohort study
James E Hartle1, Xiaoqin Tang, H Lester Kirchner
1Nephrology Department, Geisinger Medical Center, Danville, PA, USA.
Insights
Bisphosphonate therapy in women with chronic kidney disease (CKD) was linked to reduced mortality but did not significantly lower cardiovascular event risk. Further research is needed to confirm these findings and explore mechanisms.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Accelerated vascular calcification is a major contributor to cardiovascular disease (CVD) in chronic kidney disease (CKD) patients.
- Bisphosphonate therapy is being investigated for its potential to mitigate these risks.
Purpose of the Study:
- To investigate the association between bisphosphonate therapy and the risk of mortality and cardiovascular events in adult women with stage 3 or 4 CKD.
Main Methods:
- A retrospective cohort study analyzed data from 9,604 women with CKD.
- Exposure was defined by outpatient bisphosphonate prescription from electronic health records.
- Outcomes included time to death and composite cardiovascular events (myocardial infarction, heart failure, stroke).
Main Results:
- Bisphosphonate treatment was associated with a significantly lower risk of death (adjusted HR, 0.78; P = 0.003).
- However, bisphosphonate therapy was not associated with a reduced risk of composite cardiovascular events (adjusted HR, 1.14; P = 0.2).
Conclusions:
- Bisphosphonate therapy in female CKD patients is associated with reduced mortality.
- The therapy did not show a significant association with a lower risk of cardiovascular events.
- Further studies are warranted to confirm these findings and investigate underlying mechanisms.
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.
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