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Association between the cumulative exposure to bisphosphonates and hospitalization for atherosclerotic cardiovascular
Manuela Casula1, Elena Olmastroni2, Federica Galimberti2
1Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni (Milan), Italy.
Insights
High adherence to bisphosphonate treatment significantly reduces hospitalizations for atherosclerotic cardiovascular events. This suggests potential cardiovascular benefits of bisphosphonates beyond bone health.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Gerontology
Background:
- Conflicting evidence exists regarding bisphosphonates' protective effects against atherosclerotic cardiovascular events.
- Bisphosphonates are commonly prescribed for osteoporosis, primarily affecting older populations.
Purpose of the Study:
- To investigate the association between bisphosphonate use and hospitalizations for atherosclerotic cardiovascular events.
- To evaluate the impact of bisphosphonate adherence on cardiovascular outcomes.
Main Methods:
- Retrospective cohort study of over 82,000 incident bisphosphonate users aged >40 years.
- Exposure assessed by cumulative dose (proportion of days covered, PDC) and adherence levels (low, intermediate, high).
- Multivariate Cox model used to estimate hazard ratios (HR) for cardiovascular hospitalizations.
Main Results:
- Higher bisphosphonate adherence (PDC >80%) was associated with a significant reduction in cardiovascular hospitalizations (HR 0.75 [0.71-0.81]).
- A PDC >80% showed reduced incidence for both coronary and cerebrovascular events.
- Protective effects were consistent across sex, age groups, and follow-up durations.
Conclusions:
- Strict adherence to bisphosphonate therapy correlates with improved cardiovascular outcomes.
- Bisphosphonates may offer cardiovascular benefits independent of their skeletal effects.
- Further research into the mechanisms underlying these cardiovascular benefits is warranted.
Background And Aims:
Although bisphosphonates have been suggested to protect against atherosclerotic cardiovascular (CV) events, evidence is still conflicting. We aimed at investigating the effect of bisphosphonates on hospitalizations for atherosclerotic CV events.
Methods:
We carried out a retrospective cohort study selecting subjects aged>40 years, incident users of bisphosphonates. Exposure to bisphosphonates was characterized based on cumulative doses (proportion of days covered, PDC). Treatment's adherence was classified as low (PDC≤40%), intermediate (PDC 41%-80%), or high (PDC>80%). A multivariate Cox model was fitted to estimate the association between cumulative time-dependent exposure to bisphosphonates and hospitalization for atherosclerotic CV events (hazard ratio [HR] and 95% confidence interval).
Results:
Among 82,704 new bisphosphonates users (females 87.0%, mean age 70.7 ± 10.6 years), 16.1% had a CV hospitalization during a mean follow-up of 6.5 + 2.6 years. Compared with individuals with PDC ≤40%, those exposed for 41-80% or more than 80% showed HRs of CV hospitalization of 0.95 [0.91-0.99] and 0.75 [0.71-0.81], respectively. In the sub-analysis by type of event, a PDC >80% was associated with a reduced incidence for both coronary and cerebrovascular events (HRs 0.75 [0.68-0.83] and 0.76 [0.70-0.83], respectively). The protective effect was confirmed in stratified analyses by sex and age classes, and in those performed at 1 and 3 years of follow-up.
Conclusions:
Strict adherence to bisphosphonate treatment was associated with a better CV outcome. Although further studies to investigate possible mechanisms are warranted, bisphosphonates could be considered as having a potential CV benefit beyond the effect on bones.
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