RESUMO
Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.
RESUMO
Objective To investigate the efficacy of different doses of clopidogrel combined with aspirin in the treatment of high-risk non-disabling ischaemic cerebrovascular events(HR-NICE)under the precise guidance of point-of-care testing(POCT)of cy-tochrome P-450 2C19(CYP2C19)genotype.Methods The single-center,randomised,prospective,and blinded endpoint assess-ment was used.HR-NICE patients continuously enrolled in the stroke green channel and neurology ward of Xuzhou Central Hospital from January 2021 to January 2022,and all patients scraping of the buccal mucosa will be screened for CYP2C19 loss-of-function allele car-riers by POCT.According to the random number table method,they were divided into the intensive group(clopidogrel 150mg/d)and the conventional group(clopidogrel 75mg/d)combined with aspirin(100mg/d)dual antiplatelet for 21 days.Baseline information,acute stroke Org 10172 treatment trial(TOAST)staging and 90 days modified Rankin scale(mRS)score and occurrence of adverse events and severe adverse events were collected for the two groups.The primary efficacy outcome was new stroke within 90 days and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 1301 patients were screened,of which 727 patients carried CYP2C19 loss-of-function allele,and 476 patients were included:236 patients in the intensive group and 240 patients in the conven-tional group.The differences between the two groups were not statistically significant at baseline(P>0.05);4 cases(1.7%)inthein-tensive group and 26 cases(10.8%)in the conventional group had a new stroke at 90 days.The differences between the two groups were statistically significant(χ2 = 16.827,P<0.001);0 case(0)in the intensive group and1 case(2.5%)in the conventional group had moderate to severe haemorrhage at 90 days.The differences between the two groups was not statistically significant(P>0.05).Conclu-sion In HR-NICE patients with CYP2C19 loss-of-function allele,the enhanced clopidogrel dose was more effective than the conven-tional dose in the treatment with the antiplatelet drug aspirin combined with clopidogrel,and had a consistent safety profile with no more adverse events such as bleeding.