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Guidance of antiplatelet treatment

  • Genotyping should be performed: Pro, presented by G Montalescot (Paris, FR)
  • Genotyping should be performed: Contra, presented by S Windecker (Bern, CH) - Slides, Rebuttal Slides
  • Functional assessment should be performed: Pro, presented by D J Angiolillo (Jacksonville, US) - Slides, Rebuttal Slides
  • Functional assessment should be performed: Contra, presented by A Kastrati (Munchen, DE) - Slides, Rebuttal Slides
Cardiovascular Pharmacology and Pharmacotherapy

Two very interesting debates occurred in the session on antiplatelet therapy, the first on genotyping and the second on the functional assessment of platelet aggregation.

Prof. G. Montalescot (Paris, FR) defended the "pro" position for genotyping.
It has recently been demonstrated that the single nucleotide polymorphism (SNP) CYP2C19*2 is linked to worse outcome for ACS patients, particularly in relation to a higher 30 days incidence of stent thrombosis and the data were confirmed by recent metanalysis. There are several SNP related to CYP2C19: some con-fer a loss of function (LoF) (as *2) with potential increase in ischaemic events and others a gain of function (GoF) (as *17), with potential increase in bleeding risk. Moreover, there are SNPs that are related to intestinal absorption (ABCB1), esterase (PON-1), and P2Y12 receptor function. Adding genetic information, there is an increase of the AUC of the ROC curve for stent thrombosis, in comparison with clinical information only. While the carriers of CYP2C19 treated with clopidogrel had a worse outcome, those treated with prasugrel or ticagrelor did not show any increase in events in comparison with non-carriers. Randomized clinical trials are lacking to compare an adjusted treatment with genotype available vs. a classic treatment without available genotype.

Prof. S. Windecker (Bern, CH) defended the "contra" position against genotyping.
There is no difference in MACE with the LoS polymorphism and also in stent thrombosis with GoF, as well as no differences in outcome in the PLATO trial, with respect to any LoF polymorphism. In any case, the CYP2C19*2 explains no more that 12% of the variability of the response to clopidogrel and the association of stent thrombosis and LoF was subjected to bias from small studies. Stent thrombosis is anyway multifactorial and genotype is only one of the elements. Moreover, the influence of genotyping is much reduced with the new generation of stents, in comparison with the old one. As therapy is concerned, no differences according to genotyping (CYP2C19 LoF) have been shown in TRITON for prasugrel and in PLATO for ticagrelor. In the current NSTEACS ESC guidelines, genotyping has a IIbB recommendation, suggesting its use in selected cases, while the FDA box warning only alerts the availability of the test.

Prof. D. Angiolillo (Jacksonville, USA) defended the "pro" position for functional assessment.
There are a large number of studies demonstrating a wide variability in the antiplatelet effect of clopidogrel. Prasugrel and ticagrelor demonstrated that a strategy of enhancing antiplatelet effect is useful in patients with high platelet reactivity; other possibilities are to increase the clopidogrel dose or to add a third drug (as a Gp IIb/IIa inhibitor-GPI). Among the methods of assessment of platelet function, VASP and LTA have several limitations, while VerifyNow is much more user-friendly. Used in the GRAVITAS trial, however, functional assessment did not demonstrate any advantage in guiding a therapy of enhanced clopidogrel dose. On the contrary, the RECLOSE 2-ACS trial showed a reduced 3 year survival in patients with high residual platelet reactivity; adding a GPI to clopidogrel-resistant patients reduced the cardiovascular events in the follow-up. The ARCTIC trial is currently investigating the possible advantage of a strategy of monitoring platelet response to ASA and PY212 and to adjust the therapy accordingly vs. usual care without any control.

Dr. A. Kastrati (Munich, DE) defended the "contra" position against functional assessment.
Any screening test should distinguish between high and low risk patients, be accurate in the results, lead to treatment that could improve outcome and be cost-effective. Unfortunately, this is not the case of monitor-ing the antiplatelet effects of clopidogrel. There is a multitude of tests, but poor consistency, and even if it is true that poor responders have more stent thrombosis, the absolute number of events is very small. Doubling the dose of clopidogrel reduced the non-responders, but does not change the clinical outcome (OASIS 7), even when the therapy is guided by platelet functional analysis (GRAVITAS). ACCF/AHA alert states that the evidence base is insufficient to recommend platelet function testing at the present time and anyway it has to be considered that for patients with ACS (55% of all the CAD patients), the use of new PY212 inhibitors overcome the need for platelet functional tests.




Guidance of antiplatelet treatment

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.