Use of prasugrel vs clopidogrel and outcomes in patients with and without diabetes mellitus presenting with acute coronary syndrome undergoing percutaneous coronary intervention

Faggioni, Michela; Baber, Usman; Chandrasekhar, Jaya; Sartori, Samantha; Claessen, Bimmer E.; Rao, Sunil V.; Vogel, Birgit; Effron, Mark B.; Poddar, Kanhaiya L.; Farhan, Serdar; Kini, Annapoorna; Weintraub, William S.; Toma, Catalin; Sorrentino, Sabato; Weiss, Sandra; Snyder, Clayton; Muhlestein, Joseph B.; Kapadia, Samir; Keller, Stuart; Strauss, Craig; Aquino, Melissa; Baker, Brian; DeFranco, Anthony; Pocock, Stuart J.; Henry, Timothy D.; Mehran, Roxana

doi:10.1016/j.ijcard.2018.10.071

Cited by 12 publications

(14 citation statements)

References 15 publications

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“…Many extrinsic factors could influence platelet activity after taking clopidogrel, such as comorbidities, drug interactions, and smoking . Among these factors, diabetes mellitus (DM) may be an important clinical factor attributed to platelet dysfunction . The mechanisms involved in hyperreactive platelets in DM patients have been suggested to be insulin deficiency, hyperglycemia, metabolic conditions, and cellular abnormalities …”

Section: Introductionmentioning

confidence: 99%

“…9 Among these factors, diabetes mellitus (DM) may be an important clinical factor attributed to platelet dysfunction. 10 The mechanisms involved in hyperreactive platelets in DM patients have been suggested to be insulin deficiency, hyperglycemia, metabolic conditions, and cellular abnormalities. 11 The glucokinase gene (GCK), sited on 7p15.3-p15.1, codes the glucose enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Association ofGCKgene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients

Zheng

et al. 2019

Clinical Laboratory Analysis

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Backgrounds Clopidogrel resistance (CR), which was manifested as the failure of platelet inhibition in clopidogrel treatment, was likely to lead to cardiovascular events. Our study was aimed to explore the contribution of DNA methylation in glucokinase (GCK) to the CR risk. Methods Among 36 CR and 36 non‐CR acute coronary syndrome (ACS) patients, the platelet functions were evaluated by VerifyNow P2Y12 assay (turbidimetric‐based optical detection) and DNA methylation levels on two fragments of the CGI from the GCK were investigated through bisulfite pyrosequencing methods. In addition, the GCK mRNA expression was analyzed via quantitative real‐time PCR. Lastly, the logistic regression was employed to test the interaction between GCK methylation and nongenetic variables in CR patients. Results Subunit analysis showed that in male patients without DM but suffering from dyslipidemia, the increased methylation of cg18492943 indicated a risk of poor clopidogrel response (male, NCR vs CR(%): 84.86 ± 6.29 vs 88.16 ± 4.32, P = .032; without DM, NCR vs CR (%): 84.66 ± 6.18 vs 88.16 ± 4.17, P = .029; and dyslipidemia, NCR vs CR (%): 83.81 ± 6.96 vs 88.39 ± 4.74, P = .042).In addition, GCK mRNA expression was reduced in CR patients without DM. Moreover, regression analysis indicated that the values of platelet distribution width (PDW), total cholesterol (TC), and uric acid (UA) were correlated with the incidence of CR, and hypertension lowered the CR risk. Conclusions A higher methylation of cg18492943 in GCK gene would lower the expression of GCK mRNA, which might contribute to CR in patients without DM. Meanwhile, PDW and TC might be risk factors in CR.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association ofGCKgene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients

Zheng

et al. 2019

Clinical Laboratory Analysis

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“…For that reason, we performed an individual subanalysis in the diabetic population and observed that patients treated with clopidogrel had higher rate of adverse events compared with patients treated with novel P2Y 12 inhibitors without differences in bleeding events. In the PROMETHEUS multicentre study that involved 19,919 patients, 7580 (38%) of them with diabetes, Faggioni etal observed that the use of prasugrel in diabetic patients after PCI‐treated ACS was lower than in non‐diabetic patients, although there were patients with high cardiovascular risk. These results are in concordance with our results.…”

Section: Discussionmentioning

confidence: 99%

One‐year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry

Ruiz-Nodar

Esteve‐Pastor

Rivera‐Caravaca

et al. 2020

Brit J Clinical Pharma

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Background: Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y 12 inhibitors in current clinical practice patients discharged after ACS. Methods:We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted.Results: Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y 12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y 12 inhibitors group (P < .001). After 1 year of follow-up, 64 (5.0%/year) patients had a new myocardial infarction, 127 (10.0%/year) had a major adverse cardiovascular event (MACE) and 78 (6.1%/year) died. Patients treated with clopidogrel had a The authors confirm that the Principal Investigator for this paper is J.M.R.-N. All patients included in the ACHILLES registry, 1717 patients, provided individual signed informed consent and an external independent audit of the registry data (independent clinical research organization) was performed evaluating the correct inclusion of the patients, data analysed, compliance with the ethical principles and the presence of all signed informed consent of the patients included.

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“…No patient in the group aspirin plus prasugrel had a history of major or minor bleeding. In diabetics, aspirin plus prasugrel was the less prescribed association, according to recent published data [14].…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet treatment in acute coronary syndrome patients: Real-world data from the START-Antiplatelet Italian Registry

et al. 2019

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Background Despite great advances with the introduction of ticagrelor and prasugrel in the treatment of acute coronary syndromes (ACS), the risk of thrombosis and bleeding remains significant and affects the choice of clinicians in the treatment of the single patient. Large registries are effective tools to explore patterns of drug administration and adherence to guideline recommendations in real-world clinical practice. Methods START- antiplatelet is a prospective, observational registry carried out by seven Italian cardiology institutions on patients admitted for ACS aimed to document the real world treatment of ACS patients, adding also data on 12-month follow-up. We present data on the first 1050 patients who have completed 1-year follow-up on a total of 1537 patients. Primary end-points were: 1) MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) including all-cause and cardiovascular mortality, non fatal MI, urgent revascularization, TIA and ischemic stroke; 2) Major and minor bleeding according to TIMI, GUSTO and ISTH classifications Results The dual antiplatelet treatment most prescribed was aspirin plus ticagrelor (47.9%) and aspirin plus clopidogrel (32.1%). At a mean follow-up was 335±131 days, both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality. Both prasugrel and ticagrelor do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel. Patients with monotherapy had significantly higher incidence of both ischemic stroke and major bleedings. Discussion The analysis of the register has documented that both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality but both do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel.

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Use of prasugrel vs clopidogrel and outcomes in patients with and without diabetes mellitus presenting with acute coronary syndrome undergoing percutaneous coronary intervention

Cited by 12 publications

References 15 publications

Association ofGCKgene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients

Association ofGCKgene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients

One‐year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry

Antiplatelet treatment in acute coronary syndrome patients: Real-world data from the START-Antiplatelet Italian Registry

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