GRAVITAS in print: high-dose clopidogrel does not reduce mortality risk post-PCI
MedWire News: Using high-dose clopidogrel in patients who have high on-treatment reactivity after percutaneous coronary intervention (PCI) does not reduce their mortality risk after stenting compared with standard-dose clopidogrel, findings from the GRAVITAS study show.
The results, initially presented during the 2010 American Heart Association Scientific Sessions and reported by MedWire News at the time, appear in this week's JAMA.
"The results from GRAVITAS do not support a uniform strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," say Matthew Price (Scripps Translation Science Institute, La Jolla, California, USA) and team.
Instead, they advise that "alternative treatment strategies incorporating platelet function testing merit further investigation."
The GRAVITAS (Gauging Responsiveness with A VerifyNow assay - Impact on Thrombosis And Safety) study involved 2214 patients who demonstrated high on-clopidogrel platelet reactivity, defined as P2Y12 reactivity units ≥230 on VerifyNow P2Y12 assay, 12 to 24 hours after PCI with a drug-eluting stent (DES).
The patients were randomly assigned to receive high-dose clopidogrel (600 mg loading dose, 150 mg daily maintenance dose; n=1109) or standard-dose clopidogrel (no loading dose, 75 mg daily maintenance; n=1105).
After a treatment period of 6 months, Price et al observed no significant inter-group difference in the combined risk for death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis, which occurred at a low rate of 2.3% in both groups.
No significant difference in the safety endpoint of moderate or severe bleeding, as defined by Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria, was noted between the two groups. Such bleeding occurred at a 6-month rate of 1.4% versus 2.3% in the high- and standard-dose groups, respectively.
In an accompanying editorial, Paul Gurbel and Udaya Tantry, from the Sinai Hospital of Baltimore in Maryland, USA, suggested that "because the intervention used in GRAVITAS was unable to alter patient outcomes, more work is needed before personalized antiplatelet therapy can be recommended."
They concluded: "Even though GRAVITAS demonstrated that platelet function testing after DES does not improve outcomes in high-dose clopidogrel is used as the remedy, it is hoped that future studies different evaluating platelet function cutoff points and more potent P2Y12 inhibitors will be effective."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Lauretta Ihonor