Genotype-guided Antiplatelet Therapy Research Articles

Role of Cyp2c19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Identification of a reliable discriminatory test to accurately stratify patient responses to antiplatelet therapy following coronary revascularization has become increasingly desirable to optimize therapeutic efficacy and safety. The expansion of platelet function testing to include genotype assessment has been an evolutionary journey, initially fraught with confounding results. However, more recent and rigorous data analysis suggests that genotype testing- guided, tailored antiplatelet therapy may hold promise in optimizing treatment of patients after coronary intervention. Current evidence increasingly supports the use of genotype guided CYP2C19 testing to better match the post coronary intervention patient with the most efficacious and least risky antiplatelet inhibitor. The risk stratification of poor, intermediate, and good metabolizers of these drugs with such testing promises to yield clinical dividends in terms of morbidity, mortality and cost control, in this growing patient population.

Cost-Effectiveness Analysis of Genotype-Guided Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention in Korea

Cost-Effectiveness Analysis of Genotype-Guided Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention in Korea

Implementation of clopidogrel pharmacogenetic clinical decision support for a preemptive return of results program.

To describe our experiences implementing and iterating CYP2C19 genotype-guided clopidogrel pharmacogenetic clinical decision support (CDS) tools over time in the setting of a large health system-wide, preemptive pharmacogenomics program. Clopidogrel-treated patients who are genetically predicted cytochrome P450 isozyme 2C19 (CYP2C19) intermediate or poor metabolizers have an increased risk of atherothrombotic events, some of which can be life-threatening. The Clinical Pharmacogenetics Implementation Consortium provides guidance for the use of clopidogrel based on CYP2C19 genotype in patients with cardiovascular and cerebrovascular diseases. Our multidisciplinary team implemented an automated, interruptive alert that fires when clopidogrel is ordered or refilled for biobank participants with structured CYP2C19 intermediate or poor metabolizer genomic indicators in the electronic health record. The implementation began with a narrow cardiovascular indication and setting and was then scaled in 4 primary dimensions: (1) clinical indication; (2) availability across health-system locations; (3) care venue (e.g., inpatient vs outpatient); and (4) provider groups (eg, cardiology and neurology). We iterated our approach over time based on evolving clinical evidence and proactive strategies to optimize CDS maintenance and sustainability. A key facilitator of expansion was socialization of the broader pharmacogenomics initiative among our academic medical center community, accompanied by clinician acceptance of pharmacogenetic alerts in practice. A multidisciplinary collaboration is recommended to facilitate the use of CYP2C19 genotype-guided antiplatelet therapy in patients with cardiovascular and cerebrovascular diseases. Evolving clopidogrel pharmacogenetic evidence necessitates thoughtful iteration of implementation efforts and strategies to optimize long-term maintenance and sustainability.

The clinical implementation of a de-escalation strategy using CYP2C19 genotyping in patients with an acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background Current guidelines recommend prasugrel and ticagrelor in patients undergoing percutaneous coronary intervention (PCI), however these potent P2Y12-inhibitors are associated with a higher bleeding risk when compared to clopidogrel. The CYP2C19 gene influences the efficacy of clopidogrel, with carriers of loss-of-function alleles having a higher risk for major adverse cardiovascular events. A genotype-guided strategy whereby noncarriers are treated with clopidogrel has been shown to reduce bleeding without increasing the risk of major adverse cardiovascular events and to be cost-effective. Currently, there are no practical guidelines for implementing a genotype-guided strategy and there are still operational issues regarding the usage of buccal swabs or venous blood samples. Purpose The study aimed to assess the feasibility of a CYP2C19 genotype-guided de-escalation strategy in acute coronary syndrome (ACS) patients treated with dual antiplatelet therapy and to evaluate the de-escalation rate. Methods ACS patients receiving genotype-guided antiplatelet therapy from August 2021 onwards were eligible. Genotyping was done using buccal swabs in a point-of-care (POC) device or by venous blood samples in the lab. Genotyping results were entered into the EHR. Attending physicians received automatic notifications to change antiplatelet therapy based on genotyping results, but subsequent management was at their discretion. The primary endpoint is maintenance therapy with P2Y12 inhibitors, with secondary endpoints being therapy changes, and time until genotype results. Therapy changes based on genotyping method were assessed using the Chi-square and Mann-Witney U test. Results In total, 1,530 patients with suspected ACS were included in the FORCE-ACS registry from June 2021 to January 2023. A CYP2C19 genotype test was performed in 738 ticagrelor treated patients and 260 (35%) patients carried a CYP2C19 LoF-allele. The median time to genetic test result was 6.2 hours, with 84.6% of results known within 24 hours for POCT and 15.4% for blood analysis. Of all 478 CYP2C19 LoF-allele noncarriers eligible for de-escalation, 433 (90.4%) patients were successfully de-escalated from ticagrelor to clopidogrel. De-escalation to clopidogrel occurred within 24 hours in 70.9% of patients and within 48 hours in 93.1%. The time to de-escalation was significantly lower in patients analyzed using POCT (25.4 hours) compared to blood analysis (58.9 hours). Conclusion The implementation of routine genotyping is feasible and de-escalation rates to clopidogrel in non-carriers are acceptable. The quicker time-to-results and de-escalation highlights the potential benefits of using POC testing.Overview of genotype-guided strategy

Genotype-Guided Antiplatelet Therapy After Coronary Intervention in Patients With High Bleeding Risk ― Never Judge a Book by Its Cover ―

Genotype-Guided Antiplatelet Therapy After Coronary Intervention in Patients With High Bleeding Risk ― Never Judge a Book by Its Cover ―

Pharmacogenetics of P2Y12 receptor inhibitors.

Oral P2Y12 inhibitors are commonly prescribed for cardiovascular disease and include clopidogrel, prasugrel, and ticagrelor. Each of these drugs has its strengths and weaknesses. Prasugrel and ticagrelor are more potent inhibitors of platelet aggregation and were shown to be superior to clopidogrel in preventing major adverse cardiovascular events after an acute coronary syndrome and percutaneous coronary intervention (PCI) in the absence of genotyping. However, both are associated with an increased risk for non-coronary artery bypass-related bleeding. Clopidogrel is a prodrug requiring bioactivation, primarily via the CYP2C19 enzyme. Approximately 30% of individuals have a CYP2C19 no function allele and decreased or no CYP2C19 enzyme activity. Clopidogrel-treated carriers of a CYP2C19 no function allele have decreased exposure to the clopidogrel active metabolite and lesser inhibition of platelet aggregation, which likely contributed to reduced clopidogrel efficacy in clinical trials. The pharmacogenetic data for clopidogrel are most robust in the setting of PCI, but evidence is accumulating for other indications. Guidance is available from expert consensus groups and regulatory agencies to assist with integrating genetic information into P2Y12 inhibitor prescribing decisions, and CYP2C19 genotype-guided antiplatelet therapy after PCI is one of the most common examples of clinical pharmacogenetic implementation. Herein, we review the evidence for pharmacogenetic associations with clopidogrel response and outcomes with genotype-guided P2Y12 inhibitor selection and describe guidance to assist with pharmacogenetic implementation. We also describe processes for applying genotype data for P2Y12 inhibitor therapy selection and remaining gaps in the field. Ultimately, consideration of both clinical and genetic factors may guide selection of P2Y12 inhibitor therapy that optimally balances the atherothrombotic and bleeding risks.

The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome: Insights From the FORCE-ACS Registry.

Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking. The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction. Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P < .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P < .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs. CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.

Optimizing endovascular therapy for large vessel occlusion using CYP2C19 genotype-guided antiplatelet therapy: a case report

Optimizing endovascular therapy for large vessel occlusion using CYP2C19 genotype-guided antiplatelet therapy: a case report

Evaluation of race and ethnicity disparities in outcome studies of CYP2C19 genotype-guided antiplatelet therapy.

Dual antiplatelet therapy with a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin remains the standard of care for all patients undergoing percutaneous coronary intervention (PCI). It is well-established that patients carrying CYP2C19 no function alleles have impaired capacity to convert clopidogrel into its active metabolite and thus, are at higher risk of major adverse cardiovascular events (MACE). The metabolism and clinical effectiveness of prasugrel and ticagrelor are not affected by CYP2C19 genotype, and accumulating evidence from multiple randomized and observational studies demonstrates that CYP2C19 genotype-guided antiplatelet therapy following PCI improves clinical outcomes. However, most antiplatelet pharmacogenomic outcome studies to date have lacked racial and ethnic diversity. In this review, we will (1) summarize current guideline recommendations and clinical outcome evidence related to CYP2C19 genotype-guided antiplatelet therapy, (2) evaluate the presence of potential racial and ethnic disparities in the major outcome studies supporting current genotype-guided antiplatelet therapy recommendations, and (3) identify remaining knowledge gaps and future research directions necessary to advance implementation of this precision medicine strategy for dual antiplatelet therapy in diverse, real-world clinical settings.

Increased frequency of CYP2C19 loss-of-function alleles in clopidogrel-treated patients with recurrent cerebral ischemia.

Clopidogrel is used as secondary prevention after cerebral ischaemia. Previous, mainly Asian, studies have shown that genetic variations in CYP2C19 are associated with an increased risk of recurrent stroke in clopidogrel-treated patients. Evidence on the impact of this drug-gene interaction in European neurology patients is currently limited. The aim of this study is to compare the prevalence of CYP2C19 loss-of-function (LoF) alleles in a population with recurrent cerebral ischaemia to two reference groups from the same region. CYP2C19-genotyping (*2 and *3) was performed in clopidogrel-treated patients who presented with a recurrent ischaemic stroke/transient ischaemic attack (TIA). Genotype distributions were compared with two reference groups; a cohort of consecutive patients who underwent elective coronary stent implantation and a cohort of healthy Dutch volunteers. In total, 188 cases with a recurrent ischaemic event were identified, of whom 38 (20.2%) experienced an early recurrent event (24 hours to 90 days after the previous event). Among the total case group, 43.6% of the patients carried at least one CYP2C19 LoF allele, compared with 27.6% and 24.7% in respectively the cardiology and the healthy volunteers reference groups (P < .001 for both comparisons). Among the cases with an early recurrent event, 55.3% of patients were carriers of at least one CYP2C19 LoF allele (P < .0001). In this clopidogrel-treated population with recurrent cerebral ischaemia, the frequency of CYP2C19 LoF alleles was significantly higher than in reference groups, especially in early recurrent events. This study adds to the growing body of evidence that genotype-guided antiplatelet therapy could improve patient outcomes.

CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.

BackgroundStudies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss‐of‐function (LOF) variant carriers versus non‐carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real‐world outcomes with the clinical implementation of CYP2C19‐guided antiplatelet therapy after PCI.Methods and ResultsData from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all‐cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life‐threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39–0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71–1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele.ConclusionsReal‐world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update.

CYP2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 genotype impacts clopidogrel active metabolite formation. CYP2C19 intermediate and poor metabolizers who receive clopidogrel experience reduced platelet inhibition and increased risk for major adverse cardiovascular and cerebrovascular events. This guideline is an update to the 2013 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of clopidogrel based on CYP2C19 genotype and includes expanded indications for CYP2C19 genotype-guided antiplatelet therapy, increased strength of recommendation for CYP2C19 intermediate metabolizers, updated CYP2C19 genotype to phenotype translation, and evidence from an expanded literature review (updates at www.cpicpgx.org).

Genotype-Guided Antiplatelet Therapy Versus Standard Therapy for Patients with Coronary Artery Disease: An Updated Systematic Review and Meta-Analysis.

Previous studies on the efficacy and safety of genotype-guided antiplatelet therapy in patients with coronary artery disease (CAD) or undergoing percutaneous coronary intervention (PCI) have been inconclusive. We conducted a meta-analysis to evaluate if the genotype-guided antiplatelet strategy is superior to the standard therapy in patients with CAD or undergoing PCI. PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to October 1st, 2021. Studies reporting efficacy and safety outcomes in the genotype-guided treatment and standard treatment groups were included. The two groups were statistically compared. Eleven randomized controlled trials (RCTs) involving 11740 patients were included in this meta-analysis. Compared with the standard treatment group, the genotype-guided group had significant lower risks of all efficacy outcomes, including major adverse cardiovascular events (MACEs) (RR 0.60, 95%, CI 0.44-0.82, P=0.001), all-cause death (RR 0.70, 95% CI 0.51-0.95, P=0.02), cardiovascular death (RR 0.71, 95% CI 0.53-0.95, P=0.02), myocardial infarction (RR 0.53, 95% CI 0.42-0.67, P<0.0001), stroke (RR 0.64, 95% CI 0.41-0.98, P=0.04), stent thrombosis (RR 0.63, 95% CI 0.43-0.91, P=0.01) and targeted vessel revascularization (RR 0.79, 95% CI 0.67-0.92, P=0.003). There was no significant difference in any bleeding events between the two groups. As a result of the subgroup analyses, the genotype-guided treatment was more likely to reduce the incidence of MACEs in the subgroup where the proportion of patients with ACS was ≥ 90%, and subgroup of the Chinese population. Genotype-guided antiplatelet treatment could reduce the risk of MACEs without increasing the risk of bleeding events as compared with the standard treatment in patients with CAD or those undergoing PCI. In addition, Genotype-guided antiplatelet treatment might benefit Chinese population or patients with ACS.

Evaluation of race and ethnicity disparities in outcome studies of CYP2C19 genotype-guided antiplatelet therapy

Evaluation of race and ethnicity disparities in outcome studies of CYP2C19 genotype-guided antiplatelet therapy

Genotype-Guided P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention: A Bayesian Analysis.

Among patients receiving percutaneous coronary intervention (PCI), the role of a genotype-guided approach for antiplatelet therapy compared with usual care is unclear. We conducted a Bayesian analysis of the entire TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) randomized clinical trial population to evaluate the effect of the genotype-guided antiplatelet therapy post-PCI compared with the usual care on the risk of major adverse cardiovascular events (MACE). The primary outcome for our study was the composite of MACE (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included cardiovascular death, stroke, myocardial infarction, stent thrombosis, and major/minor bleeding. Bayesian modeling was used to estimate the probability of clinical benefit of genotype-guided therapy using (1) noninformative priors (ie, analyzing the TAILOR-PCI trial) and (2) informative priors derived from the ADAPT, POPular Genetics, IAC-PCI, and PHARMCLO trials (ie, analyzing TAILOR-PCI trial in the context of prior evidence). Risk ratio (RR: ratio of cumulative outcome incidence between genotype-guided and conventional therapy group) and 95% credible interval (CrI) were estimated for the study outcomes, and probability estimates for RR <1 were computed. Using noninformative priors, in TAILOR-PCI the RR for MACE was 0.78 (95% CrI, 0.55-1.07) in genotype-guided therapy after PCI, and the probability of RR <1 was 94%. Using noninformative priors, the probability of RR <1 for cardiovascular death (RR, 0.95 [95% CrI, 0.52-1.74]), stroke (RR, 0.68 [95% CrI, 0.44-1.06]), myocardial infarction (RR, 0.84 [95% CrI, 0.37-1.89]), stent thrombosis (RR, 0.75 [95% CrI, 0.37-1.45]), and major or minor bleeding (RR, 1.22 [95% CrI, 0.84-1.77]) were 57%, 96%, 67%, 81%, and 15%, respectively. Using informative priors, the posterior probability of RR <1 for MACE, from genotype-guided therapy, was 99% (RR, 0.69 [95% CrI, 0.57-0.84]). Using informative priors, the posterior probability of RR <1 for cardiovascular death (RR, 0.86 [95% CrI, 0.61-1.19]), stroke (RR, 0.69 [95% CrI, 0.48-0.99]), myocardial infarction (RR:0.56 [95% CrI, 0.40-0.78]), stent thrombosis (RR, 0.59 [95% CrI, 0.38-0.94]), and major or minor bleeding (RR, 0.84 [95% CrI, 0.70-0.99]) were 81%, 99%, 99%, 99%, and 99%, respectively. Bayesian analysis of the TAILOR-PCI trial provides clinically meaningful data on the posterior probability of reducing MACE using genotype-guided P2Y12 inhibitor therapy after PCI.

Effects of aging on clinical outcomes in patients receiving genotype‐guided P2Y12 inhibitor selection after percutaneous coronary intervention

To compare the clinical effectiveness of genotype-guided P2Y12 inhibitor selection following PCI in older patients (≥70 years) and younger patients (<70 years). Single-center, retrospective, cohort study. Risk of major adverse cardiovascular or cerebrovascular events (MACCE), defined as stent thrombosis, ischemic stroke, transient ischemic attack, non-fatal acute coronary syndrome, or cardiovascular death during 12 months after PCI, was compared across genotype and antiplatelet therapy groups by proportional hazards regression in patients ≥70 years and <70 years. 1,469 patients who underwent PCI and had CYP2C19 genotype testing at a single academic medical center. The study population was comprised of 402 (27.4%) ≥70years (older group) and 1067 (72.6%) <70years (younger group). Alternative P2Y12 inhibitors (prasugrel or ticagrelor) were used less often in the older group than the younger group in patients with a CYP2C19 no function allele (55% vs. 67%; p=0.02) and in patients without a no function allele (10% vs. 35%, p<0.001). For patients treated with clopidogrel, MACCE was significantly higher in no function allele carriers compared to those without a no function allele in the older group (19.2% vs. 12.7%; adjusted HR 2.32; 95% CI 1.07-5.05; p=0.03) and the younger group (17.4% vs. 10.4%; adjusted HR 2.01; 95% CI 1.17-3.46; p=0.01). In patients without a no function allele, MACCE risk was similar with clopidogrel compared to prasugrel or ticagrelor in the older group (adjusted HR 0.99; 95% CI 0.44-2.21; p=0.98) and the younger group (adjusted HR 1.12; 95% CI 0.72-1.74; p=0.61). This study suggests important clinical benefits of CYP2C19 genotype-guided antiplatelet therapy after PCI in both younger and older patients.

Analytical validation of GMEX rapid point-of-care CYP2C19 genotyping system for the CHANCE-2 trial

Background and purposeRapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events (HR-NICE). Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy...

Short- and long-term cost-effectiveness analysis of CYP2C19 genotype-guided therapy, universal clopidogrel, versus universal ticagrelor in post-percutaneous coronary intervention patients in Qatar

BackgroundPatients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is an effective antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI). MethodsA two-part decision-analytic model, including a one-year model and a 20-year follow-up Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/quality-adjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes, including against variations in drug acquisition costs. ResultsAgainst universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6102 /success), and dominant over the long-term. Genotype-guided therapy was dominant against universal ticagrelor over the one-year duration, and cost-effective over the long term (ICUR, USD 1383 /QALY). Universal clopidogrel was dominant over ticagrelor for the short term, and cost-effective over the long-term (ICUR, USD 10,616 /QALY). ConclusionCYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.

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.

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.

Efficacy and safety of genotype-guided antiplatelet therapy versus standard treatment in 4,604 patients with CAD after PCI: a meta-analysis of randomized controlled trials.

Objective: To compare the efficacy and safety of genotype-guided antiplatelet strategy and standard treatment in patient with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Methods: Relevant studies published in Medline, Embase, CoChrane Library were searched for randomized controlled trials (RCTs) until August 2020. Studies were screened by selection criteria, quality assessed using the Cochrane Collaboration's tool. Data were extracted from the included studies and statistically analyzed by RevMan 5.3 software. Results: Four RCTs involving 4,604 patients were included in this meta-analysis. Compared with the standard treatment group, the pooled results showed that genotype-guided group associated with lower risk of major adverse cardiovascular events (MACE, OR=0.52, 95%CI:0.35-0.78, P =0.001), any bleeding (OR=0.77, 95%CI: 0.62-0.95, P =0.02) and myocardial infarction (MI, OR=0.48, 95%CI:0.33-0.68, P <0.0001). There was no significant difference in death of any cause (OR=0.53, 95%CI: 0.18-1.54, P =0.25), cardiovascular death (OR=0.74, 95%CI:0.48-1.14, P =0.17), target vessel revascularization (OR=0.66, 95%CI:0.39-1.12, P =0.12) and major bleeding events (OR=0.86, 95%CI: 0.58-1.28, P =0.47). Conclusion: Genotype guided antiplatelet therapy could reduce the risk of MACE, MI and any bleeding events in patients with CAD undergone PCI, compared with standard treatment. Therefore, the findings support that implementation of genotype testing to tailor antiplatelet therapy after PCI.