Cilostazol-based dual anti-platelet agents for Asian patients: An updated network meta-analysis

Antiplatelet therapy, including aspirin, has been used for the secondary prevention of non-cardioembolic ischemic stroke [ [1] Park H.K. Ko S.B. Jung K.H. et al. Update of the Korean clinical practice guidelines for stroke: antithrombotic therapy for patients with acute ischemic stroke or transient ischemic attack. J. Stroke. 2022; 24: 166-175 Crossref PubMed Scopus (2) Google Scholar ]. Because patients who have a higher risk of recurrent stroke need antiplatelet agents with higher efficacy than aspirin, dual antiplatelet therapy (DAPT) has been used in cases requiring higher efficacy, such as the acute stage of stroke or high-risk patients [ [2] Wong K.S. Wang Y. Leng X. et al. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation. 2013; 128: 1656-1666 Crossref PubMed Scopus (103) Google Scholar ]. However, DAPT is notably associated with an increased risk of bleeding like a two-edged sword [ [3] Lee M. Saver J.L. Hong K.S. et al. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann. Intern. Med. 2013; 159: 463-470 Crossref PubMed Scopus (62) Google Scholar ]. Aspirin plus clopidogrel is recommended for a few weeks after acute ischemic stroke, preventing bleeding risk from not exceeding the power of preventing recurrent stroke [ [1] Park H.K. Ko S.B. Jung K.H. et al. Update of the Korean clinical practice guidelines for stroke: antithrombotic therapy for patients with acute ischemic stroke or transient ischemic attack. J. Stroke. 2022; 24: 166-175 Crossref PubMed Scopus (2) Google Scholar ]. Meanwhile, cilostazol-based DAPT has been studied for its long-term efficacy and safety profile in patients at high risk of recurrent stroke at the chronic stage of stroke because cilostazol has a high efficacy while having a lower bleeding risk than aspirin, especially in Asian patients [ [4] Jung S.J. Shim S.R. Kim B.J. et al. Antiplatelet regimens for Asian patients with ischemic stroke or transient ischemic attack: a systematic review and network meta- analysis. Ann. Transl. Med. 2021; 9: 753 Crossref PubMed Google Scholar ]. Recently, the Cilostazol Stroke Prevention Study (http://CSPS.com) trial and its subgroup analysis demonstrated that in patients at a higher risk of recurrent ischemic stroke, cilostazol-based DAPTs (cilostazol plus clopidogrel and cilostazol plus aspirin) reduced the incidence of recurrent ischemic stroke without increasing bleeding risk compared to aspirin or clopidogrel, even after used for long periods [ [5] Toyoda K. Uchiyama S. Yamaguchi T. et al. Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2019; 18: 539-548 Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar , [6] Hoshino H. Toyoda K. Omae K. et al. Dual antiplatelet therapy using Cilostazol with aspirin or Clopidogrel: subanalysis of the CSPS.com trial. Stroke. 2021; 52: 3430-3439 Crossref PubMed Scopus (4) Google Scholar ]. However, pooled results regarding the efficacy and safety of cilostazol-based DAPTs compared with those of aspirin or other antiplatelet therapies, are limited [ [7] Kim S.M. Jung J.M. Kim B.J. et al. Cilostazol mono and combination treatments in ischemic stroke: an updated systematic review and meta-analysis. Stroke. 2019; 50: 3503-3511 Crossref PubMed Scopus (24) Google Scholar ]. We performed a Bayesian network meta-analysis (NMA) to update the efficacy and safety of cilostazol-based DAPTs, reflecting the recently published studies [ [5] Toyoda K. Uchiyama S. Yamaguchi T. et al. Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2019; 18: 539-548 Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar , [6] Hoshino H. Toyoda K. Omae K. et al. Dual antiplatelet therapy using Cilostazol with aspirin or Clopidogrel: subanalysis of the CSPS.com trial. Stroke. 2021; 52: 3430-3439 Crossref PubMed Scopus (4) Google Scholar ].