CardioExchange Archive

CardioExchange, an NEJM practice community for medical professionals dedicated to improving cardiac patient care, was active from 2009 to 2015. CardioExchange fostered discussion between clinicians from across the globe.

November 16th, 2010

GRAVITAS: No Benefit for Clopidogrel Dosing Based on Platelet Function Test

The GRAVITAS (Gauging Responsiveness With A VerifyNow Assay ─ Impact on Thrombosis and Safety) trial enrolled 2214 patients with high residual platelet reactivity, as assessed by the VerifyNow P2Y12 Test measured 12 to 24 hours after the procedure. (The manufacturer of the test, Accumetrics, sponsored the trial.) Patients in the trial were randomized to either high-dose clopidogrel (additional loading dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily thereafter).

The primary endpoint ─ a composite of CV death, MI, or stent thrombosis at 6 months ─ occurred in 2.3% of patients in each group. Bleeding complications also occurred at similar rates in the groups.

“The high dose of clopidogrel doesn’t appear to improve outcomes, so alternative treatment strategies should be tested,” said Matthew Price, the lead investigator, in an AHA press release. “Many physicians have been using a high dose of clopidogrel as a default strategy in patients who are nonresponsive to the drug. We show that this strategy is probably ineffective.”

CardioExchange’s Rick Lange and David Hillis weigh in on the findings:

The GRAVITAS study shows that high-dose clopidogrel doesn’t improve outcomes in patients with high residual platelet activity. An alternative interpretation is that assessment of platelet reactivity doesn’t effectively identify individuals at high risk for a cardiovascular event following PCI.

Of all patients considered for enrollment, more than 40% had high “on-treatment platelet reactivity” (i.e., level of platelet reactivity during clopidogrel therapy), according to the VerifyNow P2Y12 Test ─ yet only 2.3% of them had a cardiovascular event in the 6 months following PCI. In essence, the positive predictive value of the test is low.  Although the investigators call for testing “alternative treatment strategies” in patients with high platelet reactivity, it may be more worthwhile first to develop tests that are better at identifying individuals at high risk of having a cardiovascular event after PCI despite routine therapy. The notion that alteration of therapy based on platelet function measurements improves outcomes is still unproven.

Would you alter antiplatelet therapy based on currently available platelet reactivity studies?  If so, how?

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One Response to “GRAVITAS: No Benefit for Clopidogrel Dosing Based on Platelet Function Test”

  1. Sanjay Kaul, MD says:
    November 16, 2010 at 6:32 pm

    The results of the GRAVITAS trial call for not only a tempering of the unbridled enthusiasm for tailored therapy using platelet function testing, but also a recalibration of our expectations of the predictive accuracies of the contemporary platelet assays. For example, 25 out of 1080 patients (2.3%) with high residual platelet reactivity (HRPR) and 8 of 586 (1.4%) without HRPR experienced adverse cardiac events yielding a sensitivity of 76%, specificity of 35%, PPV of 2%, NPV of 99%, a positive likelihood ratio of 1.17, a negative LR of 0.69, and an AUC of 0.59. These values suggest tiny to no impact of VerifyNow assay on risk prediction. Before we speculate about the role of more potent antiplatelet therapy, the research and the scientific community will be better served by developing a better mouse trap.