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Risk of acute myocardial infarction among new users of bisphosphonates: a nested case–control study

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Abstract

Objective

To test the hypothesis that bisphosphonates reduce AMI risk among new users and to assess whether the effect depends on the duration of treatment.

Methods

Case–control study nested in a primary cohort composed of patients aged 40 to 99 years, with at least 1-year registry in the BIFAP database throughout the study period 2002–2015. Out of this cohort, incident AMI cases were identified and five controls per case were randomly selected, matched by exact age, sex, and index date. The association of AMI with current, recent and past use of bisphosphonates was assessed by computing adjusted odds ratios (AOR) and their corresponding 95% confidence interval (CI) through an unconditional logistic regression. Only initiators of bisphosphonates were considered.

Results

A total of 23,590 cases of AMI and 117,612 controls were included. The mean age was 66.8 (SD 13.4) years, and 72.52% was male, in both groups. About 276 (1.17%) cases and 1458 (1.24%) controls were current users of bisphosphonates yielding an AOR of 0.98 (95% CI 0.854–1.14). Recent and past use were not associated with a reduced risk, either, nor was it found a reduction with treatment duration (AOR less than 1 year = 0.92; 95% CI 0.73–1.15; AOR more than 1 year = 1.03; 95% CI 0.86–1.23). Stratified analysis by age, sex and background cardiovascular risk did not show an effect modification by these variables.

Conclusion

The results do not support a cardioprotective effect of bisphosphonates regardless of the duration of treatment, age, sex or background cardiovascular risk. However, a small protective effect could have been masked if patients with osteoporosis have had a background higher risk of AMI.

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Acknowledgements

This study’s authors would like to thank the excellent collaboration of primary care practitioners participating in BIFAP. We also owe a debt of gratitude to the staff members of the BIFAP Unit.

Funding

BIFAP is funded and operated by the Spanish Agency for Medicines and Medical Devices (AEMPS, by its Spanish acronym). This study was supported by a research grant from Instituto de Salud Carlos III—Ministerio de Ciencia e Innovación (# PI16/01353), granted to F.d.A., co-funded by FEDER.

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Authors and Affiliations

  1. Rheumatology Unit, Hospital Universitario Fundación Alcorcón, 28922, Alcorcón, Madrid, Spain

    R. Mazzucchelli

  2. Clinical Pharmacology Unit, Hospital Universitario Príncipe de Asturias, 28805, Alcalá de Henares, Madrid, Spain

    S. Rodríguez-Martín, A. Rodriguez-Miguel, D. Barreira & F.J. de Abajo

  3. Department of Biomedical Sciences (Pharmacology), Facultad de Medicina y Ciencias de la Salud, Universidad de Alcala (IRYCIS), 28805, Alcalá de Henares, Madrid, Spain

    S. Rodríguez-Martín, A. Rodriguez-Miguel, D. Barreira & F.J. de Abajo

  4. Rheumatology Department, Hospital Universitario La Princesa, 28006, Madrid, Madrid, Spain

    A. García-Vadillo

  5. Centro de Salud La Rivota, 28922, Alcorcón, Madrid, Spain

    N. Crespí-Villarías

  6. Division of Pharmacoepidemiology and Pharmacovigilance of the Spanish Agency on Medicines and Medical Devices (AEMPS), 28022, Madrid, Spain

    M. Gil

  7. Department of Cardiology, Hospital Universitario Príncipe de Asturias, 28805, Alcalá de Henares, Madrid, Spain

    A. Garcia-Lledó

  8. Department of Medicine, Universidad de Alcalá, 28805, Alcalá de Henares, Madrid, Spain

    A. Garcia-Lledó

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  1. R. Mazzucchelli
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  2. S. Rodríguez-Martín
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  3. A. García-Vadillo
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  4. N. Crespí-Villarías
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  5. M. Gil
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  6. A. Rodriguez-Miguel
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  8. A. Garcia-Lledó
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  9. F.J. de Abajo
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Correspondence to F.J. de Abajo.

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Mazzucchelli, R., Rodríguez-Martín, S., García-Vadillo, A. et al. Risk of acute myocardial infarction among new users of bisphosphonates: a nested case–control study. Osteoporos Int 31, 2403–2412 (2020). https://doi.org/10.1007/s00198-020-05538-2

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