Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: Impact of high on‐treatment platelet reactivity and diabetes mellitus status

Capranzano, Piera; Ferreiro, José Luis; Ueno, Masashi; Capodanno, Davide; Dharmashankar, Kodlipet; Darlington, Andrew; Desai, Bhaloo; Tello‐Montoliu, Antonio; Rollini, Fabiana; Angiolillo, Dominick J.

doi:10.1002/ccd.24416

Cited by 17 publications

(6 citation statements)

References 77 publications

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“…The OPTIMUS-2 study 96 found that the addition of cilostazol to DAPT improved inhibition of platelet P2Y 12 signalling. Moreover, cilostazol might decrease platelet aggregability in patients with diabetes and HPR when taking clopidogrel 97 . Clinical benefits of cilostazol in addition to DAPT were observed in a nonrandomized study of Asian patients undergoing PCI, mainly in terms of reduced rates of target-lesion revascularization and stent thrombosis 98 ; in randomized studies, this improvement in outcomes was found to be greatest for patients with diabetes [99][100][101] .…”

Section: Acsmentioning

confidence: 99%

Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs

et al. 2018

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Diabetes mellitus is an important risk factor for a first cardiovascular event and for worse outcomes after a cardiovascular event has occurred. Cardiovascular disease in diabetes is a progressive process characterized by early endothelial dysfunction, oxidative stress, and vascular inflammation leading to monocyte recruitment and formation of foam cells and fatty streaks, which cause development of atherosclerotic plaques over years 1. Compared with atherosclerotic plaques from individuals without diabetes, those from patients with diabetes are more vulnerable (rupture-prone), and therefore, these plaques are at increased risk of developing superimposed thrombosis because of increased amounts of soft extracellular lipids, inflammation, and prothrombotic milieu; this situation predisposes patients with diabetes to acute cardiovascular events 1. Consequently, in principle, aggressive antithrombotic therapies might be associated with greater clinical benefit in patients with diabetes than in those without the condition. However, the ischaemic protection provided by antithrombotic drugs must be weighed against the drug-related bleeding risk. This Consensus Statement from the Working Group on Thrombosis of the Italian Society of Cardiology provides up-to-date recommendations on primary and secondary prevention of atherothrombotic events in patients with diabetes. We explore the mechanisms of platelet and coagulation activity and analyse the current data on the risk-benefit balance of antiplatelet therapy

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Section: Acsmentioning

confidence: 99%

Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs

et al. 2018

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“… Lee 2007 [ 34 ] 166 9 MACEs, TVR, TLR, ST, D/MI/TVR, BL and ADR. Yang 2011 [ 35 ] 154 – PRU and PA Yang 2007 [ 36 ] 55 7 PA Capranzano 2012 [ 37 ] 80 1 PRU and PRI Angiolillo 2008 [ 38 ] 40 1 PRI and PA Angiolillo 2011 [ 39 ] 106 1 PRI Ha 2013 [ 40 ] 84 2 PRU and PA Abbreviations : MACEs major adverse cardiac effects, TVR target vessel revascularization, TLR target lesion revascularization, BL bleeding, ST stent thrombosis, ADR adverse drug reactions, D death, MI myocardial infarction, PA platelet aggregation, PRI platelet reactivity index, PRU platelet reactivity unit …”

Section: Resultsmentioning

confidence: 99%

Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials

Bundhun

Qin

Chen

2015

BMC Cardiovasc Disord

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BackgroundSince antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients is very important after intracoronary stenting, and because the most commonly used therapies have been the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel and the triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol, we aim to compare the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in T2DM patients.MethodsSystematic literature search was done from the databases of PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI) and WanFang. Randomized controlled trials (RCTs) comparing the effectiveness and safety between triple therapy and dual therapy in T2DM patients after coronary stents placement were included. Endpoints included major adverse cardiac effects (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), death, stent thrombosis, bleeding and adverse drug reactions during a 9–12 months period, as well as platelet activities.ResultsFour studies including 1005 patients reporting the adverse clinical outcomes and six studies including 519 patients reporting the platelet activities, with a total of 1524 patients have been analyzed in this meta-analysis. The pooling analysis shows that TAPT has significantly decreased the occurrence of MACEs (RR: 0.55; 95 % CI: 0.36–0.86, P = 0.009), TLR (RR 0.41; 95 % CI: 0.21–0.80, P = 0.008), TVR (RR 0.55; 95 % CI: 0.34–0.88, P = 0.01) and the overall incidence of Death/ Myocardial Infarction (MI)/TVR (RR 0.54; 95 % CI: 0.31–0.94, P = 0.03) during this 9 to 12 months follow up period after stents implantation. Stent thrombosis was almost similar in both groups. Bleeding seemed to favor DAPT but the result was not statistically significant. Platelet aggregation, platelet reactivity index (PRI) and platelet reactivity unit (PRU) were also reduced with Weight Mean Difference (WMD) of (−13.80; 95 % CI: −17.03 to −10.56, P < 0.00001), (−22.87; 95 % CI: −23.66 to −22.07, P < 0.00001) and (−44.17; 95 % CI: −58.56 to −29.77, P < 0.00001) respectively.ConclusionSince MACEs have been significantly decreased in the triple group, TAPT appears to be more effective than DAPT in T2DM patients after intracoronary stenting. No significant difference in stent thrombosis and bleeding risks between these 2 groups shows TAPT to be almost as safe as DAPT in these diabetic patients.

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“…An analysis of data on the adjunctive role of cilostazol in 79 patients receiving DAPT with aspirin and clopidogrel, as per the pharmacodynamic effects of cilostazol on high on-clopidogrel platelet reactivity (HPR) levels and as per the T2D status, indicated that cilostazol reduced platelet reactivity both in HPR and non-HPR patients, and these effects were amplified in HPR patients with T2D. 146 Furthermore, cilostazol has been suggested to prevent the progression of coronary atherosclerosis in people with T2D. 147 In summary, in patients with T2D, DAPT with cilostazol and aspirin seems to be equivalent or better than clopidogrel and aspirin with lower rates of MACEs and restenosis, while triple therapy with cilostazol added to DAPT appears to be superior to DAPT with enhanced antiplatelet effect and lower restenosis rates.…”

Section: Percutaneous Coronary Interventionmentioning

confidence: 99%

Section: Coronary Artery Diseasementioning

confidence: 99%

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

Manolis

Manolis²,

Melita

et al. 2021

The Journal of Clinical Pharma

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Cilostazol, a phosphodiesterase III inhibitor, has vasodilating and antiplatelet properties with a low rate of bleeding complications. It has been used over the past 25 years for improving intermittent claudication in patients with peripheral artery disease (PAD). Cilostazol also has demonstrated efficacy in patients undergoing percutaneous revascularization procedures for both PAD and coronary artery disease. In addition to its antithrombotic and vasodilating actions, cilostazol also inhibits vascular smooth muscle cell proliferation via phosphodiesterase III inhibition, thus mitigating restenosis. Accumulated evidence has shown that cilostazol, due to its "pleiotropic" effects, is a useful, albeit underutilized, agent for both coronary artery disease and PAD. It is also potentially useful after ischemic stroke and is an alternative in those who are allergic or intolerant to classical antithrombotic agents (eg, aspirin or clopidogrel). These issues are herein reviewed together with the pharmacology and pharmacodynamics of cilostazol. Large studies and meta-analyses are presented and evaluated. Current guidelines are also discussed, and the spectrum of cilostazol's actions and therapeutic applications are illustrated.

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Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: Impact of high on‐treatment platelet reactivity and diabetes mellitus status

Abstract: Cilostazol reduces platelet reactivity both in HPR and non-HPR patients, although these PD effects are enhanced in HPR patients with DM. Nevertheless, larger studies are needed to better evaluate possible differential effects of cilostazol on platelet reactivity by diabetes status.

Cited by 17 publications

References 77 publications

Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs

Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs

Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

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