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

SummaryThe prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥50%. A total of 95 patients were available for analysis; 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA >65%). The HPR prevalence varied by each definition and ranged from 19% (PRU >235) to 68% (PRI ≥50%). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p>0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥50% (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.

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Faculty Opinions recommendation of Effects of clopidogrel therapy on whole blood platelet aggregation, the Plateletworks® assay and coagulation parameters in cats with asymptomatic hypertrophic cardiomyopathy: a pilot study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726891446.793524965 ◽

2016 ◽

Author(s):

Davide Cattano

Keyword(s):

Platelet Aggregation ◽

Hypertrophic Cardiomyopathy ◽

Pilot Study ◽

Whole Blood ◽

Blood Platelet ◽

Coagulation Parameters ◽

Clopidogrel Therapy ◽

Blood Platelet Aggregation

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Risk Factors of Recurrent Ischemic Events after Acute Noncardiogenic Ischemic Stroke

Current Pharmaceutical Design ◽

10.2174/1381612825666191029103756 ◽

2020 ◽

Vol 25 (45) ◽

pp. 4827-4834 ◽

Cited By ~ 1

Author(s):

Limin Zhang ◽

Xingang Li ◽

Dongzhi Wang ◽

Hong Lv ◽

Xuezhong Si ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Regression Analysis ◽

Ischemic Stroke ◽

Operating Characteristic ◽

Control Group ◽

Case Group ◽

Stroke Patients ◽

Clopidogrel Therapy ◽

Ischemic Events

Background: A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy. Aim: We aimed to identify risk factors for recurrent ischemic event prediction at an early stage. Methods : 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled. Vascular risk factors, routine laboratory data on admission, thromboelastography test seven days after clopidogrel therapy and any recurrent events within one year were assessed. Patients were divided into case group (patients with clinical adverse events, including ischemic stokes, transient ischemic attack, myocardial infarction and vascular related mortality) and control group (events-free patients). The risk of the recurrent ischemic events was determined by the receiver operating characteristic curve and multivariable logistic regression analysis. Results: Clinical adverse events were observed in 43 patients (case group). The mean levels of Mean Platelet Volume (MPV), Platelet/Lymphocyte Ratio (PLR), Lymphocyte Count (LY) and Fibrinogen (Fib) on admission were significantly higher in the case group as compared to the control group (P<0.001). Seven days after clopidogrel therapy, the ADP-induced platelet inhibition rate (ADP%) level was lower in the case group, while the Maximum Amplitude (MA) level was higher in the case group as compared to the control group (P<0.01). The Area Under the Curve (AUC) of receiver operating characteristic(ROC) curve of LY, PLR, , Fib, MA, ADP% and MPV were 0.602, 0.614, 0.629, 0.770, 0.800 and 0.808, respectively. The logistic regression analysis showed that MPV, ADP% and MA were indeed predictive factors. Conclusion: MPV, ADP% and MA were risk factors of recurrent ischemic events after acute noncardiogenic ischemic stroke. Urgent assessment and individual drug therapy should be offered to these patients as soon as possible.

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CYP2C19 genotype-directed P2Y12 inhibitor antiplatelet therapy normalizes risk for major adverse cardiovascular events after percutaneous coronary intervention

Indian Heart Journal ◽

10.1016/j.ihj.2021.03.004 ◽

2021 ◽

Author(s):

Tomasz P. Stys ◽

Maheedhar Gedela ◽

Smitha N. Gowda ◽

Valerie Bares ◽

Lauren Fanta ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Antiplatelet Therapy ◽

Cardiovascular Events ◽

Coronary Intervention ◽

Major Adverse Cardiovascular Events ◽

Cyp2c19 Genotype ◽

P2y12 Inhibitor ◽

Percutaneous Coronary

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Implementation and clinical outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in real-world clinical practice.

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.067 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

POD O"drisceoil ◽

TK Kiernan ◽

SA Arnous

Keyword(s):

Real World ◽

Point Of Care ◽

Coronary Intervention ◽

Buccal Swab ◽

Loss Of Function ◽

Gain Of Function ◽

Funding Sources ◽

Patients At Risk ◽

Clopidogrel Therapy ◽

Stable Cad

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUNDCYP2C19 loss-of-function (LOF) polymorphisms are associated with adverse ischaemic events after PCI. The use of a point-of-care assay (POC) to routinely genotype patients immediately post PCI could rapidly identify patients at risk of adverse cardiac outcomes. PURPOSE To investigate the incidence of CYP2C19 polymorphisms (*2, *17) and 30-day MACE in patients presenting to catheter laboratory for PCI (See table 1).METHODS We performed a single centre prospective analysis of patients presenting to a cardiac catheterisation laboratory for percutaneous coronary intervention. Participants underwent prospective rapid point-of-care genotyping of CYP2C19 major alleles (2*,17*), using the SpartanRx PCR device via buccal swab sample. All patients provided written consent. RESULTS:A total of 120 tests were performed, 51 patients were normal allele carriers (*1), 31 patients were carriers of LOF alleles (*2) and 38 patients were carriers of gain of function alleles (*17). All tests results returned in one hour. Rate of dyslipidaemia was significantly different between three groups (55% vs. 63% vs. 36%; p = 0.050). A numerically higher proportion of LOF allele carriers received clopidogrel prior to undergoing pharmacogenetic testing but this was not statistically significant (52% vs. 35% vs. 34%; p = 0.09). Two cases of MACE at 30 day follow up occurred in the loss-of-function group. Both cases received clopidogrel.CONCLUSIONSWe have demonstrated that a rapid POC of CYP2C19 testing can take place in a real-world setting. Our incidence rate of LOF carriers is concordant with international published literature. We found 52% of LOF carriers were commenced on clopidogrel therapy prior to genetic analysis. Comparison of CPY2C19 Metabolisers genotype Loss of function normal Gain of function p values baseline characteristics age in years, median (range) 65 (43-82) 64 (43-85) 65 (42-89) 0.717 Male, N (%) 21 (68%) 43 (64%) 27 (71%) 0.198 Hypertensive, N (%) 16 (52%) 29 (57%) 24 (50%) 0.623 Dyslipidaemia. N (%) 17 (55%) 32 (63%) 14 (36%) 0.050 Indication, N (%) St-Elevation MI 12 (39%) 18 (35%) 11 (29%) 0.558 NSTEMI 5 (16%) 15 (29%) 14 (37%) 0.142 Unstable Angina 5 (16%) 7 (14%) 3 (8%) 0.518 Stable CAD 9 (29%) 11 (22%) 10 (26%) 0.731 Antiplatelet, N (%) Ticagrelor 15 (48%) 33 (65%) 25 (66%) 0.09 Clopidogrel 16 (52%) 18 (35%) 13 (34%) Complication, N (%) 30-day MACE 2 (6.5%) 0 0 0.01

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