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A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial.

ABSTRACT: Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM.Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used.In patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel.

SUBMITTER: Angiolillo DJ

PROVIDER: S-EPMC3069388 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial.

Angiolillo Dominick J DJ Badimon Juan Jose JJ Saucedo Jorge F JF Frelinger Andrew L AL Michelson Alan D AD Jakubowski Joseph A JA Zhu Baojin B Ojeh Clement K CK Baker Brian A BA Effron Mark B MB

European heart journal 20110120 7

<h4>Aims</h4>Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM.<h4>Methods and results</h4>Optimizing ...[more]

PMID: 21252171

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Project description:ImportancePrasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear.ObjectiveTo investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI).Design, setting, and participantsThis study used data from the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score-matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019.ExposuresPrescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI.Main outcomes and measuresPrimary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition.ResultsOf 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (≥75 years of age, body weight <60 kg, or history of stroke or transient ischemic attack) (OR, 4.08; 95% CI, 1.86-8.97), being female (OR, 3.84; 95% CI, 1.05-14.0), or the presence of ST-segment elevation myocardial infarction (OR, 2.07; 95% CI, 1.05-4.09) or chronic kidney disease (OR, 4.78; 95% CI, 1.95-11.7).Conclusions and relevanceSince its approval, low-dose prasugrel has been used by nearly 80% of patients who undergo PCI. Despite the modified dose, bleeding events were higher among patients receiving low-dose prasugrel than among patients receiving clopidogrel, with no difference in ischemic events between the 2 groups. These results suggest the importance of a risk assessment of bleeding prior to selecting a P2Y12 inhibitor, even for the use of a lower approved dose, when treating patients of East Asian descent.

Dataset Information

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial.

Publications

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial.

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