Pharmacodynamic efficacy and safety of adjunctive cilostazol loading to clopidogrel and aspirin loading: The results of the ACCEL-LOADING (Accelerated Platelet Inhibition by Cilostazol Loading) study

Koh, Jin Sin; Kim, In Sook; Tantry, Udaya S.; Yoon, Seong Eun; Park, Yongwhi; Cho, Sang Yeong; Lee, Eun Ju; Park, Jeong Rang; Hwang, Seok Jae; Kwak, Choong Hwan; Hwang, Jin Yong; Gurbel, Paul A.; Jeong, Young Hoon

doi:10.1016/j.ijcard.2014.03.081

Cited by 5 publications

(4 citation statements)

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“…Cilostazol, a selective phosphodiesterase 3 inhibitor, is well known for its positive antiplatelet, anti-inflammatory, anti-oxidant and ischemia-reperfusion injury protective effects [11, 12]. When added to standard DAPT, cilostazol inhibits the adenosine diphosphate (ADP)-induced platelet aggregation, leading to enhanced antiplatelet effects and reduced platelet reactivity on clopidogrel [13].…”

Section: Introductionmentioning

confidence: 99%

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Hernández-Suárez

Nuñez-Medina

Scott

et al. 2018

Drug Metabolism and Personalized Therapy

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Background Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel. Methods We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n = 24) or clopidogrel alone (n = 22). Platelet function was measured ex vivo using the VerifyNow P2Y12 assay. Genomic DNA was extracted from peripheral blood samples using the QIAamp DNA Blood Midi Kit, which was subjected to candidate variant genotyping (CYP2C19, ABCB1, PON1 and P2RY12) using TaqMan quantitative polymerase chain reaction assays. All analyses were performed using SAS version 9.4 (SAS Institute). Results Among all enrolled patients, 18 (39%) had high on-treatment platelet reactivity (HTPR). The mean platelet reactivity was 207 ± 53 (range, 78–325) with higher P2Y12 reaction units in the non-cilostazol group, 224 ± 45 vs. 191 ± 55 on the cilostazol group (p = 0.03). No significant differences were observed in the clinical or genetic variables between the two groups. A multiple regression analysis determined that history of diabetes mellitus (p= 0.03), use of cilostazol (p = 0.03) and hematocrit (p = 0.02) were independent predictors of platelet reactivity. Conclusions In Puerto Rican PAD patients on clopidogrel therapy, history of diabetes mellitus, use of cilostazol and hematocrit are independent predictors of platelet reactivity. Adjunctive cilostazol therapy may enhance clopidogrel efficacy among PAD patients with HTPR.

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Section: Introductionmentioning

confidence: 99%

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Hernández-Suárez

Nuñez-Medina

Scott

et al. 2018

Drug Metabolism and Personalized Therapy

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“…В случае невозможности ее выполнения по тем или иным причинам необходимо проводить современную патогенетическую консервативную терапию, нацеленную на улучшение локального кровотока, тканевого метаболизма и реологии крови [21]. Двойная антиагрегантная терапия уже стала золотым стандартом в лечении атеросклероза и его осложнений [22].…”

Section: Discussionunclassified

The use of cilostazol in the treatment of patients with obliterating atherosclerosis on the background of diabetes mellitus

et al. 2022

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Introduction. Symptomatic peripheral arterial disease (intermittent claudication) is the main cause of disability and loss of mobility in patients and thus has a significant negative impact on their quality of life. Conservative treatment of these patients should be aimed at improving local blood flow, tissue metabolism and blood rheology. Cilostazol is the only drug with a Class I (Evidence A) recommendation for the treatment of intermittent claudication.Objective. Тo evaluate the clinical efficacy and safety of the use of cilostazol in patients with a combination of obliterating atherosclerosis of the arteries of the lower extremities and diabetes mellitus.Materials and methods. In 2021–2022, 102 patients were treated. Men – 78, women – 24, the average age was 62 ± 2.8 years. All patients were prescribed basic treatment of atherosclerosis of the arteries against the background of diabetes mellitus. In the first group (n = 52), cilostazol was additionally prescribed 100 mg 2 times a day. In the second group (n = 50), pentoxifylline was additionally prescribed 600 mg 2 times a day. The severity of the pain syndrome, the pain-free walking distance, the maximum walkable distance, the change in the ankle-shoulder index and partial oxygen pressure in the capillary blood of the foot tissues, the presence of negative outcomes were assessed after 1, 3, 6 months of treatment.Results and discussions. In group 1 patients, a more pronounced decrease in pain syndrome was noted compared to group 2, both in patients with IIA degree and in patients with IIB degree of lower limb ischemia according to Fontaine. The increase in pain-free walking distance and the maximum walking distance in group 1 were more significant than in group 2, starting from the 3rd month of treatment. The ankle-brachial index practically did not change, both in group 1 and in group 2. Negative outcomes of treatment after 6 months in the 1st group – 1.9%, and in the 2nd group – 8%.Conclusions. If it is impossible to revascularize the limb in patients with obliterating atherosclerosis of the arteries on the background of diabetes mellitus, the inclusion of cilostazol in the treatment regimen shows better final results than the appointment of pentoxifylline. The use of cilostazol significantly improved the quality of life and functional ability of the lower extremities in patients with intermittent claudication.

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“…The doses that are used include a loading dose of 200 mg and maintenance doses of 50 to 100 mg twice daily. 115…”

Section: Coronary Artery Diseasementioning

confidence: 99%

“…Cilostazol has been used in patients with CAD undergoing PCI with balloon angioplasty, and/or bare metal or drug‐eluting stent implantation, either as part of DAPT or triple therapy, in prospective and/or comparative studies (Figure 2). The doses that are used include a loading dose of 200 mg and maintenance doses of 50 to 100 mg twice daily 115 …”

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 efficacy and safety of adjunctive cilostazol loading to clopidogrel and aspirin loading: The results of the ACCEL-LOADING (Accelerated Platelet Inhibition by Cilostazol Loading) study

Cited by 5 publications

References 9 publications

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

The use of cilostazol in the treatment of patients with obliterating atherosclerosis on the background of diabetes mellitus

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

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