TY - JOUR
T1 - Comparative cardiovascular safety of strontium ranelate and bisphosphonates
T2 - a multi-database study in 5 EU countries by the EU-ADR Alliance
AU - Ali, M S
AU - Berencsi, K
AU - Marinier, K
AU - Deltour, N
AU - Perez-Guthann, S
AU - Pedersen, L
AU - Rijnbeek, P
AU - Lapi, F
AU - Simonetti, M
AU - Reyes, C
AU - Van der Lei, J
AU - Sturkenboom, M
AU - Prieto-Alhambra, D
N1 - Funding Information:
DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013-13-012). This article presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was partially supported by the NIHR Biomedical Research Centre, Oxford.
Funding Information:
This work was funded by Servier through a research grant to the EU-ADR Alliance.
Publisher Copyright:
© 2020, International Osteoporosis Foundation and National Osteoporosis Foundation.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Bone Density Conservation Agents/adverse effects
KW - Case-Control Studies
KW - Diphosphonates/adverse effects
KW - Humans
KW - Italy
KW - Netherlands
KW - Spain
KW - Thiophenes
KW - Cardiovascular death
KW - Embolism
KW - Osteoporosis
KW - Strontium ranelate
KW - Oral bisphosphonates
KW - Venous thrombosis
KW - Safety
KW - Acute myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=85089093737&partnerID=8YFLogxK
U2 - 10.1007/s00198-020-05580-0
DO - 10.1007/s00198-020-05580-0
M3 - Article
C2 - 32757044
SN - 0937-941X
VL - 31
SP - 2425
EP - 2438
JO - Osteoporosis International
JF - Osteoporosis International
IS - 12
ER -