Abstract
Summary
National registers showed that a large proportion of patients treated with strontium ranelate have conditions that may now contraindicate use. The risk of death in strontium ranelate-treated patients was significantly higher than that seen in users of other osteoporosis drugs even after adjusting for cardiovascular risk factor profile.
Introduction
The European Medicines Agency (EMA) recently warned that strontium ranelate should be avoided in patients with ischaemic heart disease (IHD), peripheral vascular disease (PVD) or cerebrovascular disease (CVD), and in patients with uncontrolled hypertension. We investigated to what extent patients beginning strontium ranelate had cardiovascular conditions and determined the rates of MI, stroke and death.
Methods
Using the Danish National Prescription Database, we identified all 3,252 patients aged 50+ who began strontium ranelate in 2005–2007 and 35,606 users of other osteoporosis drugs as controls. Hospital contacts and causes of death were retrieved from national registers.
Results
Patients starting strontium were older than patients treated with other osteoporosis drugs and more likely to suffer from IHD, PVD or CVD (combined prevalence 19.2 % in female users and 29.5 % in male users). The adjusted risk of MI was not significantly increased (women: HR 1.05 [95 % CI 0.79–1.41, p = 0.73]; men: 1.28 [0.74–2.20, p = 0.38]). For stroke, the adjusted HR was 1.23 (0.98–1.55, p = 0.07) in women and 1.64 (0.99–2.70, p = 0.05) in men. All-cause mortality was higher in strontium users (women: adjusted HR 1.20 [1.10–1.30, p < 0.001]; men: adjusted HR 1.22 [1.03–1.45, p < 0.05]).
Conclusion
Patients treated with strontium ranelate have an unfavourable cardiovascular risk profile compared with users of other osteoporosis drugs. However, only the risk of death differed significantly from the rates observed in users of other osteoporosis drugs adjusted for risk factor profile. A large proportion of patients currently treated with strontium ranelate have conditions that would now be considered contraindications according to EMA.
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References
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Conflicts of interest
BA has served as an investigator in clinical trials and on advisory boards and/or speaker panels for pharmaceutical companies that produce osteoporosis drugs (clinical trials: Amgen and NPS Pharmaceuticals; advisory boards: Amgen, Merck and Takeda-Nycomed; speakers panels: Amgen, Nycomed, Eli Lilly and Merck). PV has received unrestricted research grants and travel grants from Servier, travel grants from Novartis, Eli Lilly, and Amgen, as well as unrestricted research grants from MSD. ELG has received speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim and Pfizer and serves on advisory boards for AstraZeneca, Bayer and Bristol-Myers Squibb.
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A related article can be found at DOI 10.1007/s00198-013-2582-4; a related editorial at DOI 10.1007/s00198-013-2583-3.
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Abrahamsen, B., Grove, E.L. & Vestergaard, P. Nationwide registry-based analysis of cardiovascular risk factors and adverse outcomes in patients treated with strontium ranelate. Osteoporos Int 25, 757–762 (2014). https://doi.org/10.1007/s00198-013-2469-4
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DOI: https://doi.org/10.1007/s00198-013-2469-4