BLOGS Voices Follow

27 Feb 2011

Examining an Ad for a Platelet-Inhibition Test

I’ve recently seen in medical journals an advertisement that features an image of a clot within a stent and this headline in all capital letters: “Low Levels of Platelet Inhibition May Have Significant Consequences.” The final two words, “Significant Consequences,” are in a very large font, and the entire ad has an ominous black background.

Below the image is a bulleted list of “factors that may impact platelet inhibition”: genetic variation, concomitant medications, pre-existing conditions, and patient noncompliance. Each bullet point ends with numbered footnotes, with references appearing at the bottom of the ad.

The ad then asserts, “A simple test is available to measure platelet inhibition for patients on antiplatelet therapy.” In a larger font is the exhortation “TAKE CONTROL. TEST TODAY.”

The ad is jointly copyrighted by Daiichi Sankyo, Inc.; Lily USA; and Accumetrics. Accumetrics makes the test, and the two other companies co-developed and sell prasugrel, which inhibits platelet aggregation.

This ad clearly implies that testing for platelet inhibition is a strategy that reduces the risk for stent thrombosis. But is that really true?

What We Know

Studies have shown that thienopyridines (including clopidogrel and prasugrel) are antagonists to the P2Y12 adenosine diphosphate receptor, which is involved in platelet aggregation. As described in a 2010 ACCF/AHA clinical alert, clopidogrel is an inactive prodrug that must go through several steps to be transformed into an active metabolite. This change is mediated by the hepatic cytochrome P450 system. The relationship between clopidogrel and platelet aggregation varies among individuals, related to genes that regulate the cytochrome P450 system. In contrast, prasugrel is oxidized to its active form in a single CYP-dependent step, and its ability to inhibit platelets seems unrelated to genetic profiles associated with reduced function of the cytochrome P450 system.

What We Do Not Know

No study has shown that a strategy guided by platelet aggregation testing produces better outcomes for patients. We know that a head-to-head comparison of clopidogrel with prasugrel in the TRITON-TIMI 38 study showed that prasugrel recipients had a slightly lower risk for cardiovascular events and a slightly higher risk for major bleeding, but the participants were not selected based on platelet-inhibition response to the drugs. The investigators have not published a study showing the results stratified by genetic profile or response to the drugs. Although platelet aggregation can predict outcomes, it is not known whether using a drug that is more consistent in its platelet inhibition will be better to reduce risk for adverse events. We know that some drugs seem to be superior because of their mechanism of action but fail to actually improve patient outcomes. So although it appears logical to use a test to select a drug that is successfully inhibiting platelet aggregation, the evidence to close that loop does not exist.

The aforementioned 2010 ACCF/AHA clinical alert states clearly: “The evidence base is insufficient to recommend either routine genetic or platelet function testing at the present time.”

I wish that information were also in large capital letters in the ad.