Strontium ranelate (Protelos) and cardiovascular safety

Strontium ranelate (Protelos): New restricted indication and monitoring recommendations due to concerns regarding cardiovascular safety

An EU review coordinated by the European Medicines Agency (EMA) on the benefits and risks of strontium ranelate recently concluded recommending further restrictions in its use. The review which was initiated following concerns about cardiovascular safety was highlighted in the 54^th edition of the IMB Drug Safety Newsletter (DSN) published in May 2013 and in the June 2013 edition of MIMS Ireland.

Strontium ranelate remains contraindicated in patients with established, current or past history of ischaemic heart disease, peripheral arterial disease, cerebrovascular disease and uncontrolled hypertension. New monitoring advice has been introduced to advise prescribers to assess a patient’s risk of developing cardiovascular disease before starting treatment, monitor their risks on a regular basis during treatment and to stop treatment in any patient who develops ischaemic heart disease, peripheral arterial disease, cerebrovascular disease or uncontrolled hypertension.

Strontium ranelate is associated with an increased risk of cardiovascular disorders, including myocardial infarction. This conclusion is predominantly based on data from pooled placebo-controlled studies in postmenopausal osteoporotic patients (3,803 patients treated with strontium ranelate, corresponding to 11,270 patient-years of treatment, and 3,769 patients treated with placebo, corresponding to 11,250 patient-years of treatment). In this data set, a significant increased risk of myocardial infarction was observed in strontium ranelate treated patients as compared to placebo (1.7% versus 1.1 %), with a relative risk of 1.6 (95% CI = [1.07 ; 2.38]). There was also an increased risk of venous thrombotic and embolic events compared to placebo (1.9% versus 1.3 %), with a relative risk of 1.5 (95% CI = [1.04; 2.19]).

Regarding the benefits, efficacy data showed an effect in preventing fractures, including in patients at high risk of fracture. Strontium ranelate can be used in patients for whom treatment with other medicinal products approved for the treatment of osteoporosis is not possible due to, for example, contraindications or intolerance.

New Advice for Healthcare Professionals

• Use of strontium ranelate is restricted to treatment of severe osteoporosis in postmenopausal women and adult men at high risk of fracture, for whom treatment with other medicinal products approved for the treatment of osteoporosis is not possible due to, for example, contraindications or intolerance.

•  Strontium ranelate is contraindicated in patients with ischaemic heart disease; peripheral arterial disease and/or cerebrovascular disease; a history of these conditions or in patients with uncontrolled hypertension.

• Prescribers are advised to assess a patient’s risk of developing cardiovascular disease before starting treatment and to re-evaluate the patient’s cardiovascular risk at least every 6-12 months during treatment. Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with strontium ranelate after careful consideration of the benefit-risk balance of such treatment.

• Treatment with strontium ranelate should be discontinued in any patient who develops ischaemic heart disease, peripheral arterial disease or cerebrovascular disease, or if hypertension becomes uncontrolled.

• Healthcare professionals should review patients at a routine appointment and consider whether or not to continue treatment with strontium ranelate.