On 2016 Dec 02, Pierre Fontana commented:

Tailored antiplatelet therapy in patients at high cardiovascular risk: don’t prematurely throw the baby out with the bathwater

The clinical impact of a strategy based on a platelet function assay to adjust antiplatelet therapy has been intensively investigated. However, large prospective interventional studies failed to demonstrate the benefit of personalizing antiplatelet therapy. One of the concerns was that the interventions were delayed and partially effective, contrary to earlier smaller trials that employed incremental clopidogrel loading doses prior to PCI Tantry US, 2013 Bonello L, 2009.

Cayla and co-workers should be commended for their efforts in the ANTARCTIC trial. Although the trial is pragmatic, important limitations may account for the neutral effect of the intervention, including an antiplatelet adjustment performed between D14 and D28 after randomization. Early personalization is also supported by data from the TRITON-TIMI38 trial where half of the ischemic events (4.7/9.9%) of the prasugrel-treated arm occurred 3 days after randomization. Stratifying the analysis on the timing of events before and after D28 may provide some insight, though underpowered for a definitive conclusion.

The prognostic value of the platelet function assay and cut-off used would also be of great interest in the control group. If, the assay and cut-off values were not prognostic in this elderly population, personalization would be bound to fail.

Finally, the results of ANTARCTIC restricted to the subgroup of patients with hypertension (73% of patients), thus accumulating 3 of the risk factors related to the clinical relevance of high platelet reactivity Reny JL, 2016 would also be very interesting. Further research should not only evaluate other pharmacological approaches but also early personalization and measurement of platelet reactivity in the control group.

J.-L. Reny, MD, PhD and P. Fontana, MD, PhD

On 2016 Dec 02, Pierre Fontana commented:

Tailored antiplatelet therapy in patients at high cardiovascular risk: don’t prematurely throw the baby out with the bathwater

The clinical impact of a strategy based on a platelet function assay to adjust antiplatelet therapy has been intensively investigated. However, large prospective interventional studies failed to demonstrate the benefit of personalizing antiplatelet therapy. One of the concerns was that the interventions were delayed and partially effective, contrary to earlier smaller trials that employed incremental clopidogrel loading doses prior to PCI Tantry US, 2013 Bonello L, 2009.

Cayla and co-workers should be commended for their efforts in the ANTARCTIC trial. Although the trial is pragmatic, important limitations may account for the neutral effect of the intervention, including an antiplatelet adjustment performed between D14 and D28 after randomization. Early personalization is also supported by data from the TRITON-TIMI38 trial where half of the ischemic events (4.7/9.9%) of the prasugrel-treated arm occurred 3 days after randomization. Stratifying the analysis on the timing of events before and after D28 may provide some insight, though underpowered for a definitive conclusion.

The prognostic value of the platelet function assay and cut-off used would also be of great interest in the control group. If, the assay and cut-off values were not prognostic in this elderly population, personalization would be bound to fail.

Finally, the results of ANTARCTIC restricted to the subgroup of patients with hypertension (73% of patients), thus accumulating 3 of the risk factors related to the clinical relevance of high platelet reactivity Reny JL, 2016 would also be very interesting. Further research should not only evaluate other pharmacological approaches but also early personalization and measurement of platelet reactivity in the control group.

J.-L. Reny, MD, PhD and P. Fontana, MD, PhD