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Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death
Insights
Bisphosphonate use in chronic kidney disease (CKD) patients showed a trend toward increased cardiovascular disease (CVD) risk and a higher risk of CVD mortality, contrary to initial hypotheses. This study highlights potential risks associated with bisphosphonates in CKD populations.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Chronic kidney disease (CKD) significantly elevates cardiovascular disease (CVD) risk, potentially through vascular calcification.
- Bisphosphonates are known to inhibit vascular calcification, suggesting a potential benefit in reducing CVD risk.
Purpose of the Study:
- To investigate the association between bisphosphonate use and the risk of incident CVD, CVD-related mortality, and all-cause mortality in individuals with and without CKD.
- To test the hypothesis that bisphosphonate use in CKD patients would reduce cardiovascular and all-cause mortality.
Main Methods:
- A longitudinal observational study of 2,593 participants from the Framingham Offspring cohort.
- Propensity score-adjusted Cox regression models were used to analyze the association between bisphosphonate use and adverse outcomes.
- Participants were stratified based on CKD status (estimated glomerular filtration rate < 60 mL/min/1.73m²).
Main Results:
- In CKD patients, bisphosphonate use was associated with a trend toward increased incident CVD risk (adjusted HR 1.66) and a significantly higher risk of cardiovascular mortality (adjusted HR 2.20).
- No significant association was found between bisphosphonate use and all-cause mortality in CKD patients.
- In non-CKD individuals, bisphosphonate use was linked to increased all-cause mortality (adjusted HR 1.59) but not incident CVD or CVD-related death.
Conclusions:
- Contrary to the initial hypothesis, bisphosphonate use in CKD patients was associated with an increased trend in CVD events and a doubled risk of CVD mortality.
- Bisphosphonate use was also associated with increased all-cause mortality in individuals without CKD.
- These findings suggest potential risks of bisphosphonate use in CKD patients and warrant further investigation.
Background And Objectives:
Chronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality.
Materials And Methods:
This was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate < 60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture.
Results:
In unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93 - 2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12 - 4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27 - 1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63 - 1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36 - 1.37) in those without CKD.
Conclusion:
Contrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.
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