Cilostazol: Same Evidence, Different Conclusions

Abstract

The risk-benefit ratio of cilostazol in claudication was recently reevaluated by the European Medicines Agency (EMA).1Cilostazol-containing medicines. European Medicines Agency websitehttp://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/03/news_detail_001746.jsp&mid=WC0b01ac058004d5c1Google Scholar Around the same time, the topic was discussed during the development of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9).2Alonso-Coello P Bellmunt S McGorrian C et al.Antithrombotic therapy in peripheral artery disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141 (American College of Chest Physicians): e669S-e690SAbstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar The differences between the two entities in interpreting the evidence are of concern. Having participated in both processes, we highlight here the most important discrepancies. The EMA stated that the modest benefits of cilostazol are only greater than its risks in a limited subgroup of patients. It has restricted its use in patients with claudicant disease who have had recent coronary events or undergone coronary stent treatments and also stated cilostazol should not be given to patients also receiving two or more additional antiplatelet or anticoagulant medicines. In contrast, the AT9 panel concluded cilostazol is more likely to confer benefits than harm in patients with claudication and that the rate of adverse effects is similar to that of placebo. Confidence in the evidence, however, is low. The safety of cilostazol can be further evaluated by taking indirect evidence in coronary patients into account. In studies comparing patients receiving aspirin and thienopyridine to other patients receiving aspirin, thienopyridine, and cilostazol, the addition of cilostazol showed a protective effect in major adverse cardiovascular events (myocardial infarction, stroke, and death) and no differences in major bleeding (OR, 0.72; 95% CI, 0.60-0.86; 547 events; and OR, 1.07; 95% CI, 0.66-1.73; 68 events, respectively).3Tamhane U Meier P Chetcuti S et al.Efficacy of cilostazol in reducing restenosis in patients undergoing contemporary stent based PCI: a meta-analysis of randomised controlled trials.EuroIntervention. 2009; 5: 384-393Crossref PubMed Scopus (72) Google Scholar, 4Jang JS Jin HY Seo JS et al.A meta-analysis of randomized controlled trials appraising the efficacy and safety of cilostazol after coronary artery stent implantation.Cardiology. 2012; 122: 133-143Crossref PubMed Scopus (45) Google Scholar On what basis did the EMA restrict the drug? The EMA reevaluation was initially triggered by a safety report on cilostazol. No one disputes that drug safety reports are crucial to monitor and evaluate adverse events, but these data were not considered during the evaluation process. In our opinion, however, such action in this case was appropriate because it was unclear whether the adverse events detected in the safety report were due to the drug, to the patients' cardiovascular condition, or to other concomitant drugs. Reading the EMA recommendations, it seems that the EMA values an unlikely potential increase in the risk of adverse events—not observed to date in large randomized controlled trials—more highly than a likely improvement in the quality of life for these patients. Although we do not share the EMA's restrictions, these are not incompatible with the AT9 guidelines. We can affirm that our recommendations are still totally valid worldwide. Error in Text in: Physiologic Evaluation of the Patient With Lung Cancer Being Considered for Resectional Surgery: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice GuidelinesCHESTVol. 145Issue 2PreviewAn error appears in: “Physiologic Evaluation of the Patient With Lung Cancer Being Considered for Resectional Surgery: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines” (May 2013; 143(5_suppl): e166S-190S) The error appears in the last line of the last paragraph in the right-hand column on page e178S. The line should read low risk rather than moderate. Full-Text PDF