scholarly journals Impact of Implementing CYP2C19 Genotype-Guided Antiplatelet Therapy on P2Y12 Inhibitor Selection and Clinical Outcomes in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention: A Real-World Study in China

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Zhang ◽  
Xiu-Jin Shi ◽  
Wen-Xing Peng ◽  
Jia-Lun Han ◽  
Bai-Di Lin ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Intervention ◽  
Cyp2c19 Genotype ◽  
Bleeding Events ◽  
P2y12 Inhibitor ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
Significant Difference ◽  
Cyp2c19 Gene ◽  
Clinically Significant

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.

scholarly journals De-escalation of antiplatelets after percutaneous coronary intervention: a Bayesian network meta-analysis of various de-escalation strategies

2020 ◽  
Author(s):  
Safi U Khan ◽  
Muhammad Zia Khan ◽  
Muhammad Shahzeb Khan ◽  
Ahmed Mahmood ◽  
Ankur Kalra ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Bayesian Network ◽  
Cardiovascular Mortality ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Cochrane Library ◽  
Bleeding Events ◽  
P2y12 Inhibitor ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Abstract Aims To compare early de-escalation of dual antiplatelet therapy (DAPT) (1–3 months) to monotherapy with either P2Y12 inhibitor or aspirin vs. 12 months DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods and results Electronic databases of Medline, Embase, and Cochrane library were searched through February 2020 to identify randomized controlled trials. A Bayesian network meta-analysis was conducted with random effects model. The main endpoints of interest were cardiovascular mortality and total bleeding events. Among seven trials (35 821 patients), 52.6% patients were presented with acute coronary syndrome. A total of 3359 patients and 14 530 patients were de-escalated to aspirin and P2Y12 inhibitor monotherapy, respectively. At a median follow-up of 12 months, compared with 12 months of DAPT, there was no significant difference in cardiovascular mortality between 1-month DAPT followed by P2Y12 inhibitor monotherapy [hazard ratio (HR) 0.84 (95% credible interval 0.29–2.43)], 3 months of DAPT followed by P2Y12 inhibitor monotherapy [HR 0.74 (0.39–1.46)], or 3 months of DAPT [HR 1.00 (0.54–1.86)] followed by aspirin monotherapy. Except for de-escalation of DAPT to aspirin monotherapy after 3 months [HR 0.75 (0.43–1.20)], de-escalation to P2Y12 inhibitor monotherapy after 1 month [HR 0.28 (0.10–0.83)], or 3 months [HR 0.57 (0.33–0.98)] were associated with significant decrease in total bleeding events. There were no significant differences in terms of ischaemic endpoints among different DAPT strategies. Conclusion Early de-escalation of DAPT (1–3 months) to monotherapy with a P2Y12 inhibitor instead of aspirin might be a safer and equally effective approach compared with 12 months of DAPT in patients with PCI and DES.

scholarly journals The effect of unguided de-escalation of P2Y12 receptor inhibitor therapy after acute myocardial infarction in patients undergoing percutaneous coronary intervention: a nationwide cohort study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.S Yeh ◽  
C.Y Hsu ◽  
C.Y Huang ◽  
W.T Chen ◽  
Y.C Hsieh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Coronary Intervention ◽  
Bleeding Complications ◽  
Funding Source ◽  
P2y12 Inhibitor ◽  
Risk Of Death ◽  
Percutaneous Coronary ◽  
Significant Difference

Abstract Aims To examine the effect of de-escalation of P2Y12 inhibitor in dual antiplatelet therapy (DAPT) on major adverse cardiovascular events (MACE) and bleeding complications after acute myocardial infarction (AMI) in Taiwanese patients undergoing percutaneous coronary intervention (PCI). Methods and results We retrospectively evaluated patients who had received PCI during AMI hospitalisation and were initially on aspirin and ticagrelor and without adverse events at 3 months between 2013 and 2016. In total, 1,901 and 8,199 patients were identified as switched DAPT (switched to aspirin and clopidogrel) and unswitched DAPT (continued on aspirin and ticagrelor) cohorts, respectively. With a mean follow-up of 8 months, the incidence rates (per 100 person-year) of death, AMI readmission and MACE were 2.89, 3.68 and 4.91 in the switched cohort and 2.42, 3.28 and 4.72 in the unswitched cohort, respectively based on an inverse probability of treatment weighted method. (Table) After adjustment for patients' clinical variables, two groups were no significant difference in death (A), AMI admission (B) and MACE (C). Additionally, there was no difference in the risk of major (D) or non-major clinically relevant bleeding (E) (Figure 1). Conclusions Unguided de-escalation of P2Y12 inhibitor in DAPT was not associated with higher risk of death, MACE, AMI readmission in Taiwanese patients with AMI undergoing PCI. Figure 1 Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Taipei Medical University

scholarly journals Personalized Antiplatelet Therapy Based on CYP2C19 Genotypes in Chinese ACS Patients Undergoing PCI: A Randomized Controlled Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiujin Shi ◽  
Yunnan Zhang ◽  
Yi Zhang ◽  
Ru Zhang ◽  
Baidi Lin ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Confidence Interval ◽  
Antiplatelet Therapy ◽  
Primary Endpoint ◽  
Coronary Intervention ◽  
Chinese Patients ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Background: The clinical benefits of cytochrome P450 (CYP) 2C19 genotype-guided antiplatelet therapy in Asians remain unclear. In this study, we aimed to investigate the clinical outcomes of pharmacogenomic antiplatelet therapy in Chinese patients.Methods: Patients with acute coronary syndrome planning to undergo percutaneous coronary intervention were eligible for this study and were randomly divided into a genotype-guided treatment (GT) group and routine treatment (RT) group, with a ratio of 2:1. Patients in the GT group underwent CYP2C19 genotyping (*2 and *3 alleles), and the results were considered in selecting P2Y12 receptor inhibitors. Patients in the RT group were treated with P2Y12 receptor inhibitors according to their clinical characteristics. The primary endpoint was a composite of major adverse cardiovascular or cerebrovascular events (MACCE). The secondary endpoint was significant bleeding events.Results: Finally, 301 patients were enrolled; 75.1% were men and the mean age was 59.7 ± 9.8 years. In total, 281 patients completed the follow-up procedure. The primary endpoint occurred in 16 patients, 6 patients in the GT group and 10 in the RT group. The GT group showed lower MACCE rates than the RT group (6/189 vs. 10/92, 3.2 vs. 10.9%, hazard ratio: 0.281, 95% confidence interval: 0.102–0.773, P = 0.009). There was no statistically difference in significant bleeding events between the GT and RT groups (4.2 vs. 3.3%, hazard ratio: 1.315, 95% confidence interval: 0.349–4.956, P = 0.685).Conclusion: Personalized antiplatelet therapy that is based on CYP2C19 genotypes could decrease MACCE within a 12-month period in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000034352.

scholarly journals Impact of Thrombocytopenia on In-Hospital Outcome in Patients Undergoing Percutaneous Coronary Intervention

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhongxiu Chen ◽  
Zheng Liu ◽  
Nan Li ◽  
Ran Liu ◽  
Miye Wang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Count ◽  
Major Bleeding ◽  
Primary Outcome ◽  
Coronary Intervention ◽  
Hospital Death ◽  
Hospital Inpatient ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Background. Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI. Methods. Using the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100 × 10 9 / L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group ( ≤ 85 × 10 9 / L ), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion. Results. Of 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p = 0.029 ). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding ( BARC ≥ 2 ) (OR 2.56, 95% CI 1.24 to 5.44, p = 0.011 ). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p = 0.025 ). Conclusions. It seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.

scholarly journals Relationship of PRECISE-DAPT and DAPT scores with mortality in patients admitted with acute coronary syndrome who undergo coronary stent implantation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C Alak ◽  
E Ozpelit ◽  
D Cirgamis ◽  
M Abusharekh ◽  
N Baris
Keyword(s):  
Acute Coronary Syndrome ◽  
Major Bleeding ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
Coronary Stent Implantation ◽  
Number Of Patients ◽  
Percutaneous Coronary ◽  
Significant Difference ◽  
Relationship Of

Abstract Introduction International guidelines recommend using risk score tools that allow us to assess the risk of bleeding and ischemia when deciding on DAPT. In our research, we aimed to examine the mortality relationship of new risk scores, DAPT and PRECISE-DAPT scores. Method Between 2013–2014, 948 patients admitted to our clinic with ACS were included in our study. We excluded 688 patient (no contact number,CABG, medical treatment, use of oral anticoagulation, active malignant cancer). 260 patients admitted with acute coronary syndrome (58%, 8 STEMI, 35%, 4 non-STEMI, 5%, 4 Unstable angina pectoris) who undergo coronary stent implantation were included in the study. We aimed to focus on the patients who undergo percutaneous coronary intervention and their risk of mortality. The patients' records were retrospectively analyzed through the hospital information system and archive records. Laboratory results, echocardiography and CAG reports of the patients, disease histories were obtained from the information recorded through the system. With these data, PRECISE-DAPT and DAPT scores of patients were calculated. Results The number of patients with a PRECISE-DAPT Score ≥25 was 62 (23.8%). The number of patients with DAPT Score ≥2 was 193 (74.2%). Mortality occurred in 49 (18.8%) patients. Patients with PRECISE-DAPT ≥25 and those with PRECISE-DAPT <25 were compared in terms of mortality and mortality was significantly higher in the high-scoring group [P <0.001 OR 6.94 C (3.53–13.62)]. The patients were divided into 4 groups (PRECISE-DAPT 25 and DAPT ≥2, PRECISE-DAPT ≥25 and DAPT ≥2, PRECISE-DAPT 25 and DAPT 2, PRECISE-DAPT ≥25 and DAPT 2) according to PRECISE-DAPT and DAPT score. Mortality was significantly higher regardless of DAPT score in patients with high PRECISE-DAPT scores (p<0.001). We evaluated the relationship between PRECISE-DAPT score and major bleeding and all bleeding. Compared to the group there was no significant difference in all bleeding events (P=0.56) and major bleeding events (P=0.23). The relationship between bleeding events and mortality was evaluated. There was no significant difference in mortality (p=0.689) with all bleeding events; but mortality was significantly increased in patients with major bleeding [P=0.025 OR 6.16 (1,33–28,49)]. Conclusion In our study, we observed that the patient group with a high PRECISE-DAPT score had a high mortality rate regardless of the DAPT score. The PRECISE-DAPT score is a useful tool in determining the group with high long-term mortality in patients who present with acute coronary syndrome and undergo percutaneous coronary intervention. The clinician should use the PRECISE-DAPT score when deciding on the duration of dual antiplatelet therapy in this patient group and these patients with high scores need to be monitored more closely. The data we have obtained from our study is retrospective and these results need to be supported by prospective and large studies. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Early aspirin discontinuation following acute coronary syndrome or percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Guedeney ◽  
J Mesnier ◽  
S Sorrentino ◽  
F Abcha ◽  
M Zeitouni ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Randomized Controlled Trials ◽  
Major Bleeding ◽  
Coronary Intervention ◽  
Controlled Trials ◽  
Coronary Syndrome ◽  
Randomized Controlled ◽  
Percutaneous Coronary ◽  
Significant Difference

Abstract Background The respective ischemic and bleeding risks of early aspirin discontinuation following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains uncertain. Objectives To evaluate the safety and efficacy of early aspirin discontinuation in ACS or PCI patients treated with P2Y12 inhibitors with or without anticoagulants. Methods We performed a review of randomized controlled trials (RCTs) comparing a P2Y12 inhibitor-based single antiplatelet strategy following early aspirin discontinuation to a strategy of sustained dual antiplatelet therapy (DAPT) in ACS or PCI patients requiring or not anticoagulation for another indication. The primary safety endpoint was major bleeding while non-major bleeding and all bleeding were secondary safety endpoints. The primary efficacy endpoint was all-cause mortality while secondary efficacy endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), definite stent thrombosis (ST) or any stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. The study is registered in PROSPERO (CRD42019139576). Results We included 9 RCTs comprising 40,621 patients.Compared to prolonged DAPT, major bleeding (2.2% vs. 2.8%; RR 0.68; 95% CI: 0.54 to 0.87; p=0.002; I2: 63%), non-major bleeding (5.0% vs. 6.1%; RR: 0.66; 95% CI: 0.47 to 0.94; p=0.02; I2:87%) and all bleeding (7.4% vs. 9.9%; RR: 0.65; 95% CI: 0.53 to 0.79; p<0.0001; I2: 88%) were significantly reduced with early aspirin discontinuation (Figure 1), without significant difference for all-cause death (p=0.60), MACCE (p=0.60), MI (p=0.77), definite ST (p=0.63), and any stroke (p=0.59). Results were consistent in patients with or without anticoagulation, without significant interaction for any outcomes but MI (p=0.04). Conclusions In patients on DAPT after an ACS or a PCI, early aspirin discontinuation prevents bleeding events with no effect on the ischemic risk or mortality. Figure 1. Central illustration Funding Acknowledgement Type of funding source: None

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