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Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database

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Abstract

Summary

The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

Introduction

This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting.

Methods

This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995–2014 and 2006–2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed.

Results

A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk.

Conclusions

This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

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Data availability

The different data sources have provided the research team with data subject to different licences, which do not allow sharing.

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Acknowledgements

The authors would like to thank Marta Pineda-Moncusí for her assistance with the revision process of the manuscript.

Funding

This work was partially funded by a Project Grant from the National Osteoporosis Society. This work was supported by the NIHR Biomedical Research Centre, Oxford. DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013–13-012). Andrew Judge was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. This study has been approved by the Independent Scientific Advisory Committee (ISAC, protocol number 14_110). This study is based in part on data from the Clinical Practice Research Datalink obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data is provided by patients and collected by the NHS as part of their care and support. The interpretation and conclusions contained in this study are those of the author/s alone.

Author information

Authors and Affiliations

  1. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford, OX3 7LD, UK

    S. Khalid, S. Hawley & A. Judge

  2. Oxford NIHR Biomedical Research Centre, University of Oxford, Windmill Road, Oxford, OX3 7LD, UK

    S. Khalid, A. Sami, S. Hawley, A. Judge, C. Cooper, M. Kassim Javaid & D. Prieto-Alhambra

  3. Family and Community Medicine Teaching Unit of Granada, Cartuja University Health Centre, Andalusian Health Service (SAS), Avda. Juan Pablo II, 18001, Granada, Spain

    S. Calderon-Larranaga

  4. Centre for Primary Care, Wolfson Institute of Population Health, Queen Mary University of London, London, Turner Street, E1 2AB, UK

    S. Calderon-Larranaga & A. Judge

  5. Bristol NIHR Biomedical Research Centre, Musculoskeletal Research Unit, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK

    S. Hawley & A. Judge

  6. Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, University of Oxford, Windmill Road, Oxford, OX3 7LD, UK

    N. Arden

  7. Centre for Health Informatics, University of Manchester, Vaughan House, Portsmouth Road, Manchester, M13 9PL, UK

    T. P. Van Staa

  8. Utrecht Institute for Pharmaceutical Sciences, Utrecht University, David de Wied building, Universiteitsweg 99, 3584 CG, Utrecht, Netherlands

    T. P. Van Staa

  9. Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK

    C. Cooper

  10. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK

    C. Cooper

  11. Odense Patient Data Explorative Network OPEN, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

    B. Abrahamsen

  12. GREMPAL (Grup de Recerca en Malalties Prevalents de L’Aparell Locomotor) Research Group, CIBERFes and Idiap Jordi Gol Primary Care Research Institute, Universitat Autònoma de Barcelona and Instituto de Salud Carlos III, Gran Via de Les Corts Catalanes, 591 Atico, 08007, Barcelona, Spain

    D. Prieto-Alhambra

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  1. S. Khalid
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Corresponding author

Correspondence to S. Khalid.

Ethics declarations

Ethics approval

This study has been approved by the Independent Scientific Advisory Committee (ISAC, protocol number 14_110). Ethics approval was not required.

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The corresponding author has the right to grant on behalf of all authors and does grant on behalf of all authors, a worldwide licence to the publishers and its licensees in perpetuity, in all forms, formats and media (whether known now or created in the future), to (i) publish, reproduce, distribute, display, and store the contribution; (ii) translate the contribution into other languages, create adaptations and reprints, and include within collections and create summaries, extracts, and/or abstracts of the contribution; (iii) create any other derivative work(s) based on the contribution; (iv) exploit all subsidiary rights in the contribution; (v) the inclusion of electronic links from the contribution to third party material wherever it may be located; and (vi) licence any third party to do any or all of the above.

Transparency statement

The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned have been explained.

Disclaimer

The study funder had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. All authors had full access to all of the data in the study and take responsibility for the integrity of such data and the accuracy of the data analysis.

Conflict of interest

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare Cyrus Cooper reports Personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB. Kassim Javaid reports honoraria, unrestricted research grants, and travel and/or subsistence expenses from Amgen, Lilly UK, Shire, Internis, Consilient Health, Stirling Anglia Pharmaceuticals, Mereo Biopharma, Optasia Medical, Zebra Medical Vision, Kyowa Kirin Hakin, and UCB. Andrew Judge reports consultancy fees, lecture fees, and honoraria from Servier, UK Renal Registry, Oxford Craniofacial Unit, IDIAP Jordi Gol, and Freshfields Bruckhaus Deringer, is a member of the Data Safety and Monitoring Board (which involved receipt of fees) from Anthera Pharmaceuticals, Inc., and received consortium research grants from Roche. Bo Abrahamsen reports Institutional research grants UCB and Novartis. Advisory board and consulting fees UCB. Daniel Prieto Alhambra reports DPA’s institution received speaker fees from AMGEN and UCB Biopharma; consultancy fees from UCB Biopharma; research grants from UCB, Amgen, and Les Laboratoires Servier; and financial support to organise educational activities from Janssen (on behalf of IMI-funded EHDEN and EMIF consortiums) and Synapse Management Partners. Sara Khalid, Sara Calderon-Larranaga, Arvind Sami, Samuel Hawley, and Tjeerd P Van Staa declare that they have no conflict of interest.

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Khalid, S., Calderon-Larranaga, S., Sami, A. et al. Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database. Osteoporos Int 33, 1579–1589 (2022). https://doi.org/10.1007/s00198-021-06262-1

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