GRAVITAS: Low on-clopidogrel platelet reactivity linked to reduced CV event risk
MedWire News: A sub-analysis of the GRAVITAS trial suggests that low on-clopidogrel platelet reactivity after percutaneous coronary intervention (PCI) is linked to a reduced cardiovascular (CV) event risk.
This observation has important implications for the use of platelet function testing and individualized P2Y12 antagonist therapy in PCI patients, say Matthew Price (Scripps Clinic and Scripps Translational Science Institute, La Jolla, California, USA) and team.
As reported previously by MedWire News, the GRAVITAS (Gauging Responsiveness with A VerifyNow P2Y12 assay - Impact on Thrombosis And Safety) study included 2214 patients who demonstrated high on-clopidogrel platelet reactivity, defined as a P2Y12 reactivity unit (PRU) level ≥230 on the VerifyNow P2Y12 assay, 12-24 hours after PCI with a drug-eluting stent.
The patients were randomly assigned to receive treatment with clopidogrel 600 mg loading dose and 150 mg daily maintenance dose (high dose; n=1109) or clopidogrel 75 mg daily maintenance dose and no loading dose (standard dose; n=1105).
After a treatment period of 6 months, Price et al observed no significant intergroup difference in the primary endpoint of the combined risk for death from CV causes, nonfatal myocardial infarction (MI), or stent thrombosis, which occurred at a rate of 2.3% in the high- and standard-dose groups, or in the safety endpoint of moderate or severe bleeding (as defined by Global Use of Strategies to Open Occluded Coronary Arteries criteria).
The aim of the current analysis was to examine the relationship between CV outcomes and on-treatment platelet reactivity (OTR) over the course of the trial.
OTR was measured at 12-24 hours and at 30 days after PCI. The researchers used multivariate analysis with OTR as a time-varying covariate to determine the association between OTR and the primary endpoint.
Of the 2800 enrolled patients, 2796 had evaluable platelet function data.
The findings, reported in the journal Circulation, revealed that in unadjusted analysis an OTR of less than 208 PRU was significantly associated with an 82% lower risk for the primary endpoint at 60 days (p=0.02), and a 57% lower risk at 6 months (p=0.01), than a higher OTR.
After adjusting for potential confounders, an OTR of less than 208 PRU remained associated with a significant reduction in risk for the primary endpoint at 60 days, at a hazard ratio (HR) of 0.23 (p=0.047), while the effect tended towards significance at 6 months, at a HR of 0.54 at 6 months (p=0.065).
"We may not have been able to detect a significant association between on-treatment reactivity of less than 230 PRU and clinical outcomes because of the lower than expected rate of the primary endpoint in the trial," write the authors.
This could be due to the under-representation of patients with lower levels of on-treatment reactivity in the study population, they speculate.
Nonetheless, Price et al conclude: "The efficacy of an individualized strategy to target a level of OTR below this threshold merits investigation."
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By Piriya Mahendra