November 4th, 2012

Platelet-Function Testing in Coronary Stenting: Frozen in Its Tracks

CardioExchange editors Richard Lange and David Hillis ask an ARCTIC trial investigator to discuss possible reasons why antiplatelet-drug and dosing adjustments, guided by platelet-function testing, did not improve clinical outcomes for stented patients.


In an open-label trial from France, 2440 patients about to undergo coronary stenting were randomized to one of two strategies:

(A) a monitoring-guided approach of platelet-function testing in the catheterization lab with the VerifyNow assay (Accumetrics), followed by antiplatelet-drug (aspirin, clopidogrel, or prasugrel) and dosage adjustment for patients with inadequate inhibition. Platelet-function testing was repeated 14 to 30 days later in the outpatient clinic.

(B) a conventional approach of no platelet-function testing or corresponding drug adjustment

The monitoring-guided group had no significant improvements in clinical outcomes, relative to the conventional group.



1. Do you think the results can be explained by any of the following?

a. The test (or variables) used to define high platelet reactivity during treatment doesn’t accurately reflect platelet function or predict clinical outcome.

Montalescot: No, I think the test detects the right patients — those with high platelet reactivity, who are known to have a worse prognosis. But we may be looking at a marker of risk and not a risk factor. Or the interventions were not the right ones to alter the prognosis.

b. The additional antiplatelet treatment didn’t adequately correct the high platelet reactivity noted in some subjects.

Montalescot: We used the most potent agents available to correct the anomaly of high platelet reactivity: glycoprotein IIb/IIIa inhibitors and high doses of clopidogrel, aspirin, and (when it became available) prasugrel. We cannot exclude the possibility that some of these interventions might be deleterious — e.g., GPIIb/IIIa inhibitors have been shown to have agonistic effects in certain situations.

c. We’re chasing the wrong car (i.e., treating platelet reactivity doesn’t really matter).

Montalescot: Again, we may be looking at a marker of risk and not a risk factor that, when modified, is associated with better outcomes. Platelet reactivity has been used as a surrogate endpoint in many intervention studies with antiplatelet agents, and we know the limits of surrogate endpoints. We will need more data to unravel all the hypotheses.


2.  In the trial, only 27% of patients (those at highest risk) had an ACS. Was bedside monitoring of platelet reactivity helpful in this group?

Montalescot: ACS patients were a prespecified subgroup, and the results were the same in this subgroup as in the rest of the cohort.


3. About 90% of the thienopyridine-treated patients received clopidogrel. Do you think the results (i.e., no significant improvement in clinical outcomes with platelet-function monitoring and treatment adjustment) would be similar for the newer antiplatelet agents?

Montalescot: That is a possibility, but it needs to be tested in a new study. Prasugrel was not available when we started to enroll patients, nor ticagrelor. When prasugrel became available, we had an amendment to use it in the study, but keep in mind that we are talking about off-label use for these drugs anyway.


Share your thoughts and questions about the findings from the ARCTIC trial.

For perspective on the ARCTIC trial from Journal Watch Cardiology‘s Dr. Howard C. Herrmann, click here.

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