RESUMO
Objective: To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with long-term clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). Methods: In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated. Results: CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes (P < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% vs. 11.7% vs. 22.1%, P < 0.05) or poor metabolizer (10.7% vs. 16.4% vs. 22.6%, P = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, P < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs (P > 0.05). Conclusions: Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone.
RESUMO
BACKGROUND: Remote ischemic conditioning (RIC) is used to protect against myocardial injury. However, there is no adequate evidence for comprehensive RIC in elderly patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to test whether comprehensive RIC, started pre-primary percutaneous coronary intervention (PPCI) and repeated daily on 1-30 days post-PPCI, can improve myocardial salvage index (SI), left ventricular ejection fraction (LVEF), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and 6-min walk test distance (6MWD) in elderly patients with acute STEMI during 12 months follow-up. METHODS: 328 consenting elderly patients were randomized to receive standard PPCI plus comprehensive RIC (the treatment group) or standard PPCI (the control group). SI at 5-7 days after PPCI, LVEF, left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), KCCQ-CSS, 6MWD and adverse events rates were measured and assessed. RESULTS: SI was significantly higher in the treatment group [interquartile range (IQR): 0.38-0.66, P = 0.037]. There were no significant differences in major adverse events at 12 months. Although the differences of LVEDVI, LVESVI and LVEF between the treatment group and the control group did not reach statistical significance at 6 months and 12 months, LVEF tended to be higher, LVEDVI tended to be lower in the treatment group. The KCCQ-CSS was significantly higher in the treatment group at 1 month (IQR: 46.5-87, P = 0.001) and 12 months (IQR: 55-93, P = 0.008). There was significant difference in 6MWD between the treatment group and the control group (IQR: 258-360 vs. IQR: 250-345, P = 0.002) at 1 month and (IQR: 360-445 vs. IQR: 345-432, P = 0.035) at 12 months. A modest correlation was found between SI and LVEF (r = 0.452, P < 0.01), KCCQ-CSS ( r = 0.440, P < 0.01) and 6MWD ( r = 0.384, P < 0.01) respectively at 12 months. CONCLUSIONS: The comprehensive RIC can improve SI, KCCQ-CSS and 6MWD. It may be an adjunctive therapy to PPCI in elderly patients with STEMI.