Impact of GEne Polymorphisms, Platelet REactivity and the SYNTAX Score on 1-Year Clinical Outcomes in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: The GEPRESS Study

Study Questions:

Does the SYNTAX score help predict which patients with high platelet reactivity (HPR) will develop a major adverse cardiac event (MACE)?

Methods:

A total of 1,053 patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI) and treated with clopidogrel were studied prospectively. Platelet reactivity index (PRI) was measured before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertile ≥15). MACE in the period between 1 month and 1 year was the primary endpoint.

Results:

One-month HPR was an independent predictor of MACE in patients with an SS ≥15, but not in those with an SS <15, displaying a fivefold increase in event rates (10.4% vs. 2.5%; p < 0.0001). CYP2C19*2 was the only single nucleotide polymorphism associated with HPR, but it was not associated with MACE. Predischarge HPR and SS effectively stratified the risk of subsequent MACE up to 1-year follow-up.

Conclusions:

In clopidogrel-treated patients with NSTEACS undergoing PCI, HPR was independently associated with an increased risk of MACE only in the presence of a high SS.

Perspective:

The SYNTAX score is an angiographic grading tool to stratify the complexity of coronary disease. The utility of HPR in patients undergoing PCI is controversial. This study suggests that adding a measure of coronary disease complexity to platelet studies improves MACE prediction. More potent antiplatelet strategies may improve outcomes in this high-risk group, although this will need to be proven in future studies.

Keywords: Acute Coronary Syndrome, Follow-Up Studies, Polymorphism, Single Nucleotide, Ticlopidine, Blood Platelets, Percutaneous Coronary Intervention


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