1. Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR Alliance
- Author
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Klara Berencsi, J van der Lei, Monica Simonetti, Carlen Reyes, N Deltour, Daniel Prieto-Alhambra, P Rijnbeek, K Marinier, Miriam C. J. M. Sturkenboom, M S Ali, S Perez-Guthann, Francesco Lapi, Lars Pedersen, and Medical Informatics
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Embolism ,030209 endocrinology & metabolism ,Thiophenes ,Acute myocardial infarction ,VALIDATION ,03 medical and health sciences ,0302 clinical medicine ,Strontium ranelate ,Internal medicine ,Venous thrombosis ,Medicine ,Humans ,Myocardial infarction ,Netherlands ,RISK ,VENOUS THROMBOEMBOLISM ,Bone Density Conservation Agents ,Diphosphonates ,business.industry ,Oral bisphosphonates ,Confounding ,Absolute risk reduction ,Odds ratio ,Bisphosphonate ,CARE ,medicine.disease ,Confidence interval ,Italy ,Spain ,Case-Control Studies ,Cohort ,Cardiovascular death ,Osteoporosis ,030101 anatomy & morphology ,Safety ,business ,medicine.drug - 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.
- Published
- 2020
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