Skip to main content
Erschienen in: Osteoporosis International 12/2020

05.08.2020 | Original Article

Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR Alliance

verfasst von: M.S. Ali, K. Berencsi, K. Marinier, N. Deltour, S. Perez-Guthann, L. Pedersen, P. Rijnbeek, F. Lapi, M. Simonetti, C. Reyes, J. Van der Lei, M. Sturkenboom, D. Prieto-Alhambra

Erschienen in: Osteoporosis International | Ausgabe 12/2020

Einloggen, um Zugang zu erhalten

Abstract

Summary

Strontium ranelate use, compared with oral bisphosphonates, is not associated with increased risk of AMI in patients with no contraindications for SR use. However, current strontium ranelate (compared with current bisphosphonate) appears associated with 25–30% excess risk of VTE and 35% excess risk of CVDeath.

Introduction

Evaluate the risk of cardiac and thromboembolic events among new users of SR and oral BPs without contraindications for SR.

Methods

We conducted three multi-national, multi-database (Aarhus-Denmark, HSD-Italy, IPCI-Netherlands, SIDIAP-Spain, THIN-UK) case-control studies nested within a cohort of new users of SR/BP. We matched cases of acute myocardial infarction (AMI), venous thromboembolism (VTE), and cardiovascular death (CVDeath), up to 10 controls on gender, year of birth, index date, and country. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) according to current SR vs current BP use and current vs past SR use, adjusting for potential confounders. Data were pooled using random effects meta-analysis.

Results

No excess risk of AMI (5477 cases/54,674 controls) was found with current SR vs current BP (OR 0.89 (95%CI 0.70, 1.12)) nor with current vs past SR use (0.71(0.56, 0.91)). For VTE (5614 cases/6036 controls), an excess risk was found with current SR compared with current BP use, 1.24 (0.96, 1.61), and current vs past SR use, 1.30 (1.04, 1.62). For CVDeath (3019 cases/29,871 controls), an increased risk was seen with current SR vs current BP use, 1.35 (1.02, 1.80), but not with current vs past SR use (0.68 (0.48, 0.96)).

Conclusion

In patients without contraindications for SR, we found no evidence of an increased risk of AMI but a 25–30% excess risk of VTE and a 35% excess risk of CVDeath with current SR vs current BP users. This is despite a reduction in risk in CVDeath with current vs past SR users. The latter disparity could still be partially explained by cessation of preventative therapies in end-of-life or residual confounding by indication.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat European Medicines Agency (2013) PSUR assessment report. EMA/PRAC/136656/2013. Strontium ranelate European Medicines Agency (2013) PSUR assessment report. EMA/PRAC/136656/2013. Strontium ranelate
2.
Zurück zum Zitat European Medicines Agency (2013) Recommendation to restrict the use of Protelos / Osseor (strontium ranelate) European Medicines Agency (2013) Recommendation to restrict the use of Protelos / Osseor (strontium ranelate)
3.
Zurück zum Zitat European Medicines Agency (2014) Protelos/Osseor to remain available but with further restrictions European Medicines Agency (2014) Protelos/Osseor to remain available but with further restrictions
4.
Zurück zum Zitat European Medicines Agency (2014) Protelos and Osseor. CHMP scientific conclusions and PRAC Assessment report of the Review under Article 20 of Regulation (EC) No 726/2004 European Medicines Agency (2014) Protelos and Osseor. CHMP scientific conclusions and PRAC Assessment report of the Review under Article 20 of Regulation (EC) No 726/2004
5.
Zurück zum Zitat Abrahamsen B, Grove E, Vestergaard P (2014) Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate. Osteoporos Int 25(2):757–762CrossRef Abrahamsen B, Grove E, Vestergaard P (2014) Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate. Osteoporos Int 25(2):757–762CrossRef
6.
Zurück zum Zitat Svanström H, Pasternak B, Hviid A (2014) Use of strontium ranelate and risk of acute coronary syndrome: cohort study. Ann Rheum Dis 73(6):1037–1043CrossRef Svanström H, Pasternak B, Hviid A (2014) Use of strontium ranelate and risk of acute coronary syndrome: cohort study. Ann Rheum Dis 73(6):1037–1043CrossRef
7.
Zurück zum Zitat Cooper C, Fox K, Borer J (2014) Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: a nested case–control study in the CPRD. Osteoporos Int 25(2):737–745CrossRef Cooper C, Fox K, Borer J (2014) Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: a nested case–control study in the CPRD. Osteoporos Int 25(2):737–745CrossRef
8.
Zurück zum Zitat Coloma PM, Valkhoff VE, Mazzaglia G, Nielsson MS, Pedersen L, Molokhia M, Mosseveld M, Morabito P, Schuemie MJ, van der Lei J, Sturkenboom M, Trifirò G, on behalf of the EU-ADR Consortium (2013) Identification of acute myocardial infarction from electronic healthcare records using different disease coding systems: a validation study in three European countries. BMJ Open 3(6):e002862CrossRef Coloma PM, Valkhoff VE, Mazzaglia G, Nielsson MS, Pedersen L, Molokhia M, Mosseveld M, Morabito P, Schuemie MJ, van der Lei J, Sturkenboom M, Trifirò G, on behalf of the EU-ADR Consortium (2013) Identification of acute myocardial infarction from electronic healthcare records using different disease coding systems: a validation study in three European countries. BMJ Open 3(6):e002862CrossRef
9.
Zurück zum Zitat Ramos R, Balló E, Marrugat J, Elosua R, Sala J, Grau M, Vila J, Bolíbar B, García-Gil M, Martí R, Fina F, Hermosilla E, Rosell M, Muñoz MA, Prieto-Alhambra D, Quesada M (2012) Validity for use in research on vascular diseases of the SIDIAP (information system for the development of research in primary care): the EMMA study. Rev Esp Cardiol (English Edition) 65(1):29–37CrossRef Ramos R, Balló E, Marrugat J, Elosua R, Sala J, Grau M, Vila J, Bolíbar B, García-Gil M, Martí R, Fina F, Hermosilla E, Rosell M, Muñoz MA, Prieto-Alhambra D, Quesada M (2012) Validity for use in research on vascular diseases of the SIDIAP (information system for the development of research in primary care): the EMMA study. Rev Esp Cardiol (English Edition) 65(1):29–37CrossRef
10.
Zurück zum Zitat Lawrenson R, Todd JC, Leydon G, Williams T, Farmer R (2000) Validation of the diagnosis of venous thromboembolism in general practice database studies. Br J Clin Pharmacol 49(6):591–596CrossRef Lawrenson R, Todd JC, Leydon G, Williams T, Farmer R (2000) Validation of the diagnosis of venous thromboembolism in general practice database studies. Br J Clin Pharmacol 49(6):591–596CrossRef
11.
Zurück zum Zitat Severinsen MT, Kristensen SR, Overvad K, Dethlefsen C, Tjønneland A, Johnsen SP (2010) Venous thromboembolism discharge diagnoses in the Danish National Patient Registry should be used with caution. J Clin Epidemiol 63(2):223–228CrossRef Severinsen MT, Kristensen SR, Overvad K, Dethlefsen C, Tjønneland A, Johnsen SP (2010) Venous thromboembolism discharge diagnoses in the Danish National Patient Registry should be used with caution. J Clin Epidemiol 63(2):223–228CrossRef
12.
Zurück zum Zitat Reyes C, Aragon M, Rijnbeek P, van der Lei J, Verhamme K, Prieto-Alhambra D (2018) Validation of COPD ICD10 diagnostic codes in the SIDIAP primary health care research database using a combination of spirometry measures, symptoms, drug use, and free text review. Value Health 21:S368CrossRef Reyes C, Aragon M, Rijnbeek P, van der Lei J, Verhamme K, Prieto-Alhambra D (2018) Validation of COPD ICD10 diagnostic codes in the SIDIAP primary health care research database using a combination of spirometry measures, symptoms, drug use, and free text review. Value Health 21:S368CrossRef
13.
Zurück zum Zitat R Core Team (2013) R: A language and environment for statistical computing R Core Team (2013) R: A language and environment for statistical computing
14.
Zurück zum Zitat Berencsi K, Sami A, Ali MS, Marinier K, Deltour N, Perez-Gutthann S, Pedersen L, Rijnbeek P, van der Lei J, Lapi F, Simonetti M, Reyes C, Sturkenboom MCJM, Prieto-Alhambra D (2020) Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance. Osteoporos Int 31(4):721–755CrossRef Berencsi K, Sami A, Ali MS, Marinier K, Deltour N, Perez-Gutthann S, Pedersen L, Rijnbeek P, van der Lei J, Lapi F, Simonetti M, Reyes C, Sturkenboom MCJM, Prieto-Alhambra D (2020) Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance. Osteoporos Int 31(4):721–755CrossRef
15.
Zurück zum Zitat Martín-Merino E, Petersen I, Hawley S et al (2018) Risk of venous thromboembolism among users of different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK. Osteoporos Int 29(2):467–478 Martín-Merino E, Petersen I, Hawley S et al (2018) Risk of venous thromboembolism among users of different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK. Osteoporos Int 29(2):467–478
16.
Zurück zum Zitat Sing C-W, Wong AYS, Kiel DP et al (2018) Association of alendronate and risk of cardiovascular events in patients with hip fracture. J Bone Miner Res 33(8):1422–1434CrossRef Sing C-W, Wong AYS, Kiel DP et al (2018) Association of alendronate and risk of cardiovascular events in patients with hip fracture. J Bone Miner Res 33(8):1422–1434CrossRef
Metadaten
Titel
Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR Alliance
verfasst von
M.S. Ali
K. Berencsi
K. Marinier
N. Deltour
S. Perez-Guthann
L. Pedersen
P. Rijnbeek
F. Lapi
M. Simonetti
C. Reyes
J. Van der Lei
M. Sturkenboom
D. Prieto-Alhambra
Publikationsdatum
05.08.2020
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 12/2020
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-020-05580-0

Weitere Artikel der Ausgabe 12/2020

Osteoporosis International 12/2020 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.