Presented: ICPE 2025 in Washington DC, USA
Authors: Tzu-Hsuan Yang, Rebecca Persson, Zarena Jafry, Katrina Wilcox Hagberg, Catherine Vasilakis-Scaramozza, Susan S Jick
Abstract
Background: Information on safety of osteoporosis treatments with respect to major cardiovascular disease (CVD) outcomes, including myocardial infarction (MI), is important information for patients and clinicians choosing between treatment options.
Objective: To describe the risks of MI among female users of various osteoporosis treatments.
Methods: We conducted a cohort study of female users of osteoporosis treatments, age 40–89, in the Clinical Practice Research Datalink Aurum (2000–2020). Exposed patients were those with a first prescription for a bisphosphonate (alendronate, ibandronate, risedronate, zoledronic acid, etidronate), denosumab, raloxifene, teriparatide or calcitonin in 2000 or later. The common reference group was comprised of patients with an osteoporosis-related code and vitamin D (Vit D) prescriptions in 2000 or later. Patients with a history of CVD were excluded. Person-time was accumulated by study drug from first prescription through censor date (event, other CVD diagnosis, major comorbidity, age 90, death, end of record, or 31 Dec 2020). A patient was considered currently exposed from prescription date through prescription duration + 30 days. We calculated incidence rates (IRs) per 10,000 patient-years (PY) of MI for each osteoporosis treatment. We also estimated adjusted incidence rate ratios (adjIRRs) with 95% confidence intervals (CI) for each exposure, controlling for age, calendar year, osteoporotic disease type and smoking status, compared with Vit D-only group.
Results: Among 306,457 patients (median age 68 years [interquartile range, IQR, 59–77], median follow-up 6 years [IQR 3–11]), there were 3,846 MI cases. Most exposure was alendronate (77%) or risedronate (12%). No MI cases were observed among current users of teriparatide or calcitonin. The IR across all exposures for MI was 22.7 per 10,000 PY. The IR was highest for current users of ibandronate (IR = 33.0 [95% CI 25.4–42.2]) and etidronate (IR = 29.9 [23.3–37.8]) and lowest for current users of raloxifene (IR = 9.7 [5.9–15.2]). Rates for current users of other bisphosphonates or denosumab ranged from 24.6 to 26.7 per 10,000 PY. Adjusted IRRs were comparable to the Vit D group for most study drugs, except for ibandronate. MI incidence was 50% higher among all ibandronate users compared to the Vit D group (adjIRR = 1.50 [1.16–1.95]), rising to 80% higher in patients aged 75 years and older (adjIRR = 1.80 [1.36–2.38]).
Conclusion: Risk of MI was slightly elevated among current ibandronate users compared to untreated patients with Vit D prescriptions only. Risk of MI was similar for all other study drugs. Since there are few studies with which to compare these results, future studies are needed.
Online Methods Appendix
Data Resource: United Kingdom (UK) Clinical Practice Research Datalink (CPRD) Aurum, general practice database, and linked Hospital Episode Statistics, in-patient database
Study Population: Female patients aged 40-89 in CPRD Aurum 2000-2020 with no history of cardiovascular disease in two cohorts:
- Treated cohort: new users of osteoporosis treatments: alendronate, ibandronate, risedronate, zoledronic acid, etidronate, denosumab, raloxifene, teriparatide, calcitonin
- Untreated cohort: prescribed vitamin D (VitD) users with osteoporosis-related clinical codes (osteoporosis, osteopenia, or osteoporosis monitoring)
Cohort Entry Definition:
- Treated cohort:date of the first ever osteoporosis treatment
- Untreated cohort: first VitD prescription on or after age 40 with an osteoporosis-related code (osteoporosis, osteopenia, dual-energy X-ray absorptiometry tests, monitoring, supporting codes) recorded at any time before or up to 90 days after.
Exposure Definition: Current use of each osteoporosis treatment was calculated based on recorded durations, quantities, and instructions (oral treatments) or standard dosing schedules (infusions and injections). We assigned exposure for each day from cohort entry through censor to mutually exclusive categories of study drug use. Exposure categories were osteoporosis treatment monotherapy (separately), 2+ osteoporosis treatment (concomitant use or overlap of exposed time during treatment switching [results for this small exposure category not presented in poster]), past use of any osteoporosis treatment (no current use), and VitD only.
Follow-up: Person-time was accumulated by exposure category from cohort entry until the earliest of MI diagnosis or censor date (any cardiovascular diagnosis, major comorbidity, age 90, death, end of record, or 31 December 2020).
Case Definition: Identified all patients with myocardial infarction (MI) diagnosis code recorded in CPRD Aurum or in a HES primary diagnosis field at least 7 days after cohort entry. MI diagnoses were also included as cases if recorded after censoring due to death or if recorded within 7 days after censoring due to angina, acute coronary syndrome or unspecified ischemic heart disease. MI diagnoses were not included as cases if recorded within 30 days after a major non-cardiac surgery was recorded.
Case exposure was assigned as the study drug exposed on MI date minus 7 days.
Statistical Analysis: For each exposure, we estimated incidence rates with 95% confidence intervals (CIs) and incidence rate ratios (adjusted for age, calendar year, osteoporotic disease type, and smoking status) with 95% CI compared to VitD only (common reference group).
