Reasons for the Failure of Platelet Function Testing to Adjust Antiplatelet Therapy: Pharmacodynamic Insights From the ARCTIC Study.

Abstract

BACKGROUND:

In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment.

METHODS:

We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y12 test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status.

RESULTS:

Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74-1.18]; P=0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22-7.59]; P=0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40-1.58]; P=0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96-8.41]; P=0.06) in HPR versus non-HPR patients.

CONCLUSIONS:

The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov. Unique identifier: NCT00827411.

• Authors: Benoit Lattuca, Johanne Silvain, Yan Yan, Christophe Pouillot, Thomas Cuisset, Guillaume Cayla, Patrick Henry, Abdourahmane Diallo, Simon Elhadad, Grégoire Rangé, Thibault Lhermusier, Ziad Boueri, Pascal Motreff, Didier Carrié, Eric Vicaut, Gilles Montalescot, Jean-Philippe Collet
• Journal: Circulation. Cardiovascular interventions (Circ Cardiovasc Interv) Vol. 12 Issue 11 Pg. e007749 (11 2019) ISSN: 1941-7632 [Electronic] United States
• PMID: 31694410 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• P2RY12 protein, human
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Receptors, Purinergic P2Y12

Topics

• Aged
• Blood Platelets (drug effects, metabolism)
• Clinical Decision-Making
• Coronary Thrombosis (blood, etiology, prevention & control)
• Drug Monitoring (methods)
• Drug-Eluting Stents
• Female
• Hemorrhage (chemically induced)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (blood, etiology, prevention & control)
• Percutaneous Coronary Intervention (adverse effects, instrumentation, mortality)
• Platelet Activation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage, adverse effects)
• Platelet Function Tests
• Predictive Value of Tests
• Purinergic P2Y Receptor Antagonists (administration & dosage, adverse effects)
• Receptors, Purinergic P2Y12 (blood, drug effects)
• Risk Assessment
• Risk Factors
• Stroke (blood, etiology, prevention & control)
• Time Factors
• Treatment Outcome