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

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

Affiliations

¹Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK

²Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

³Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark

⁴Department of Pharmacoepidemiology and Real World Evidence, Servier, Suresnes, France

⁵RTI Health Solutions, Barcelona, Spain

⁶Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands

⁷Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy

⁸GREMPAL Research Group, Idiap Jordi Gol Primary Care Research Institute and CIBERFes, Universitat Autonoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain

⁹Julius Global Health, University Medical Center, Utrecht, Netherlands

Abstract and keywords

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.

Keywords: Acute myocardial infarction; Cardiovascular death; Embolism; Oral bisphosphonates; Osteoporosis; Safety; Strontium ranelate; Venous thrombosis

Links

DOI: 10.1007/s00198-020-05580-0

PubMed: 32757044

WoS: 000556142400001

History

Received: 2020-02-12

Accepted: 2020-07-30

Online: 2020-08-05

Cited Works (1)

Year	Entry
2020	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. 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. April 2020;31(4):721-755.