Key result
Prasugrel shows no benefit over clopidogrel for major events after elective PCI in stable CAD.
Why the study?
The extent to which prasugrel can correct high on-treatment platelet reactivity and improve clinical outcomes in patients undergoing elective PCI is unknown.
RCT (n=423)
randomly assigned
Absolute Event Rate: 0% vs 0.47%
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“If you have a low event rate and you're using a therapy that only gets about half of patients with high reactivity down below the cutpoint, the chances of seeing a clinical effect are scant. If they had chosen a lower cutpoint and used a more effective drug, they”
“although on-treatment platelet reactivity has now been established as a marker of risk among clopidogrel-treated patients, platelet-function testing is still unlikely to become routine clinical practice until it has been demonstrated that lowering platelet reactivity with medication can improve clinical outcome, and so far this has not been successfully shown”
“Even though GRAVITAS demonstrated that platelet function testing after drug-eluting stent placement does not improve outcomes if high-dose clopidogrel is used as the remedy, it is hoped that future studies evaluating different platelet-function cut points and more potent P2Y12 inhibitors will be effective.”
Randomized trial evaluates ischemic outcomes of prasugrel versus clopidogrel in patients with high platelet reactivity after elective stenting, highlighting very low event rates in stable disease.
OBJECTIVES: This study sought to investigate the efficacy, safety, and antiplatelet effect of prasugrel as compared with clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after elective percutaneous coronary intervention (PCI). BACKGROUND: The extent to which prasugrel can correct HTPR and improve clinical outcomes in patients undergoing elective PCI is unknown. METHODS: Stable coronary artery disease (CAD) patients with HTPR (>208 P2Y(12) reaction units [PRU] by the VerifyNow test) after elective PCI with at least 1 drug-eluting stent (DES) were randomly assigned to either prasugrel 10 mg daily or clopidogrel 75 mg daily. Platelet reactivity of the patients on the study drug was reassessed at 3 and 6 months. The study was stopped prematurely for futility because of a lower than expected incidence of the primary endpoint. RESULTS: In 212 patients assigned to prasugrel, PRU decreased from 245 (225 to 273) (median [interquartile range]) at baseline to 80 (42 to 124) at 3 months, whereas in 211 patients assigned to clopidogrel, PRU decreased from 249 (225 to 277) to 241 (194 to 275) (p < 0.001 vs. prasugrel). The primary efficacy endpoint of cardiac death or myocardial infarction at 6 months occurred in no patient on prasugrel versus 1 on clopidogrel. The primary safety endpoint of non-coronary artery bypass graft Thrombolysis In Myocardial Infarction major bleeding at 6 months occurred in 3 patients (1.4%) on prasugrel versus 1 (0.5%) on clopidogrel. CONCLUSIONS: Switching from clopidogrel to prasugrel in patients with HTPR afforded effective platelet inhibition. However, given the low rate of adverse ischemic events after PCI with contemporary DES in stable CAD, the clinical utility of this strategy could not be demonstrated.
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Trenk et al. (2012) conducted an RCT in Stable coronary artery disease with high on-treatment platelet reactivity (n=423). Prasugrel vs. Clopidogrel 75 mg daily was evaluated on cardiac death or myocardial infarction at 6 months.
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