Determining Effectiveness of Risk-Minimization Measures

Impact of Risk Minimization Measures on the Use of Cilostazol in Europe

J Castellsague, B Calingaert, B Poblador-Plou, M Giner-Soriano, M Linder, O Scholle, A Arana Navarro, C Bui, C Laguna, A Prados-Torres, A Roso-Llorach, S Perez-Gutthann


Cilostazol is indicated in Europe to improve walking distances in patients with intermittent claudication. It has been associated with spontaneous reports of serious bleeding and cardiovascular effects, including heart attacks, anginas, and arrhythmias.

In 2013, the European Medicines Agency evaluated the benefits and risks of cilostazol and recommended risk-minimization measures, including labeling changes and communication to healthcare professionals.

Cilostazol's use was restricted to second-line therapy in case lifestyle modifications, including smoking cessation and exercise programs, failed to improve symptoms. It was contraindicated in patients with unstable angina pectoris myocardial infarction or coronary intervention within the last 6 months, or in patients with concomitant treatment with two or more additional antiplatelet agents such as aspirin or clopidogrel.

In this observational study, RTI Health Solutions collaborated with research institutions to evaluate the effectiveness of such measures on new users of cilostazol in Europe. The study was conducted in 5 European populations - Aragon and Catalonia in Spain, Sweden, Germany, and the United Kingdom.

The frequency of patients with conditions mentioned in labeling changes were compared for the period before and after the implementation of the risk-minimization measures in 2013. After labeling changes, the annual prevalence of cilostazol decreased in all the study populations. The highest reduction was 57% in Catalonia.

Prevalence of smoking before initiation decreased only in Spain. Cardiovascular contraindications decreased in all study populations, and use of 2 or more antiplatelet drugs decreased in the United Kingdom, Spain, and Sweden. Overall, this study indicates that the risk-minimization measures implemented for the use of cilostazol in 2013 were effective in all the study populations. Smoking cessation before initiating cilostazol remains an area of improvement.