ABSTRACT
Background: CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel in patients undergoing percutaneous coronary intervention for acute coronary syndrome. However, the clinical impact of implementing CYP2C19 gene-guided pharmacotherapy is unclear, especially among the Chinese population. The purpose of this study was to evaluate P2Y12 receptor inhibitor selection and clinical outcomes upon implementation of CYP2C19 genotype-guided pharmacotherapy in current clinical practice. Methods: This was a single-center observational cohort study. Adult percutaneous coronary intervention patients who received CYP2C19 genetic testing (*2, *3, *17 alleles) were included. Ticagrelor was recommended for patients with a LOF allele. Factors related to P2Y12 inhibitor selection were determined by logistic regression. The primary endpoint was major cardiac or cerebrovascular adverse events (MACCE) within 12 months. MACCE and clinically significant bleeding events (BARC ≥2) in the LOF-clopidogrel group, non-LOF-clopidogrel group, and non-LOF-ticagrelor group were compared with those in the LOF-ticagrelor group. The inverse probability of treatment weighting (IPTW) was adjusted in a Cox regression analysis to eliminate confounding factors. Results: Among 1,361 patients, 826 (60.7%) had a LOF allele. Patients with a LOF allele were more likely to be prescribed ticagrelor (multivariate-adjusted OR 1.349; 95% CI 1.040 to 1.751; p = 0.024). The MACCE rate was higher in the LOF-clopidogrel group than in the LOF-ticagrelor group (7.8 vs. 4.0%; log-rank p = 0.029; IPTW-adjusted HR 2.138; 95% CI 1.300-3.515). Compared with the LOF-ticagrelor group, the non-LOF-clopidogrel group showed no significant difference in MACCE rate (5.8 vs. 4.0%; log-rank p = 0.272; IPTW-adjusted HR 1.531; 95% CI 0.864-2.714). Among the patients treated with ticagrelor, there was no significant difference in the MACCE rate between the LOF group and non-LOF group (4.3 vs. 4.0%; log-rank p = 0.846; IPTW-adjusted HR 1.184; 95% CI 0.582-2.410). There was no significant difference in the incidence of clinically significant bleeding events among the four groups. Conclusion: This study confirms that efficiently returned CYP2C19 genotype results did partially guide cardiologists to prescribe ticagrelor for patients with a LOF allele, and that clopidogrel had a higher risk of MACCE than ticagrelor in these patients, which provides support for the implementation of CYP2C19 gene-guided antiplatelet therapy in clinical practice.
ABSTRACT
In this study, the effects of iso-osmotic solution of Mg (NO3) 2 and NaCl on seedling growth, leaf lipid peroxidation, antioxidant enzyme activities, and osmotic adjustment substance accumulation were investigated using three cucumber cultivars with different ecotypes. Then salt tolerance was evaluated by membership function method. The results revealed that under the stress of 60 and 80 mmol x L(-1) Mg(NO3) 2 solution and its isotonic 90 and 120 mmol x L(-1) NaCl solution, the seedling traits such as height, stem diameter, leaf area, fresh and dry mass of aerial part and underground parts, and antioxidant enzymes activity were obviously decreased with the increasing concentration of Mg( NO3)2 and its isotonic NaCl in the three cucumber cultivars. Moreover, the inhibitory effects became more obvious with the increasing concentration of either Mg(NO3)2 or NaCl solution. MDA content and membrane lipid peroxidation were enhanced in cucumber seedlings. Among the three cultivars, SJ31-1 changed less than the other two cultivars regarding the reduced amplitudes of biomass, and activity of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the increased amplitude of MDA. In addition, Mg (NO3)2 solution inhibited seedling growth more strongly than isotonic NaCl solution did, such difference was relatively significant with increasing the concentration of solution. The contents of proline, soluble amino acids, and soluble sugars varied depending on the cucumber genotype and salt type. The increased amplitude of proline content was the largest in SJ31-1, and that of soluble sugars was the largest in Lubai 19 when growing under salt treatment. The change of these parameters in Xintaimici was in between. Soluble sugars and soluble proteins were predominant osmolytes unde NaCl stress, whereas proline and soluble proteins were main osmolytes under Mg (NO3) 2 stress. Comprehensive evaluation showed that salt tolerance of the three cucumber cultivars was in order of SJ31-1 > Xintaimici > Lubai 19.
