Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Objectives: High on-treatment platelet reactivity (HPR) has emerged as a risk factor for stent thrombosis and major adverse cardiovascular events (MACE) in patients who receive Clopidogrel after percutaneous coronary intervention (PCI). In the present study, we sought to investigate the following; 1) the association between platelet reactivity and the SS for the risk of MACE in patients with ACS undergoing PCI treated with Clopidogrel; 2) the association between genetic variants involved in Clopidogrel-mediated platelet effects and the risk of MACE; 3) the incremental prognostic value of the platelet reactivity measured at several time points. Methods: Eighty four (84) consecutive in-patients who were admitted with ACS undergoing PCI at our center were enrolled. Out of 84 patients the data of 72 patients were finally analysed for genetic analysis, 59 patients were on clopidogrel and follow up done for one year. All patients were required to receive aspirin 325 mg/day indefinitely and a 600-mg loading dose of Clopidogrel followed by 75 mg/day for at least 12 months.The determination of platelet aggregation was done by using a platelet aggregometer (chronolog). > 46 and <19 HPR (high platelet reactivity) and LPR in the setting of PCI have been defined by ROC curve analyses was taken, Genomic DNA was isolated by salting out procedure. Specific primers were designed for CYP2C19∗2 SNP by primerblast tool and PCR was carried out. The primary objective of this study was to investigate the risk of MACE (cardiac mortality, MI, and stent thrombosis) with 1-month HPR and the SS in the period between 1 month and 1 year. Secondary endpoints included all-cause death, cardiac death, MI, cardiac death/MI, stent thrombosis, and bleeding determined in the peri-procedural period, between hospital discharge and 1 month, and between 1 month and 1 year. The impact of genetic variants of Clopidogrel metabolism on the risk of MACE was determined as well. Results: Finally 59 patients were included in the study. Follow up was done at 30 days and at regular intervals up to 12 months. Out of 59 cases 23 patients were in the lower SYNTAX score tertiles SS < 15, 36 patients in the upper tertiles (SS >15). In this study, mean survival free days from MACE computed using Kaplan Meier Analysis have shown that the time to MACE was 320 days for patients with HPR<46 and SS<15 and 365 days in patients without HPR >46 and SS<15 while it was 302 days for patients with HPR<46 and SS>15 and 322 days with HPR >46 and SS>15, indicating that patients with SS>15 are more likely to suffer an early event (MACE) though not statistically significant. By cox regression analysis for MACE, it was found that there was 2.66 fold more hazard of developing MACE though statistically not significant with increase in syntax score at 1 month [HR-2.66 (0.14-50.85.), p = 0.57], and HPR 0.25 [HR-0.25 (0.02-3.59.)p = 0.31],Of note no association was apparent between the risk of MACE at any time point and Cyp2c 19∗1/∗2,cyp2c19∗2∗2. Net clinical outcomes (MACE and BARC bleeding) PRU at 30 days <46 arbitrary aggregation units was 8 cases and >46 was 5 cases respectively. Conclusions: HPR is associated with increased rates of ischemic event only in patients with high SS suggesting a possible setting in which platelet function testing could be implemented to optimize antiplatelet theraphy. CYP2C19∗2was the only genetic variant significantly associated HPR but not associated with the risk of MACE.