Patients with acute coronary syndrome (ACS) and left ventricular (LV) dysfunction undergoing percutaneous coronary intervention (PCI) need adequate antithrombotic protection. We aim to compare the clinical outcomes between ticagrelor and clopidogrel in these patients. In total, 336 patients with ACS and LV dysfunction who undergoing PCI were included in this retrospective observational study. Of these, 137 received clopidogrel and 199 received ticagrelor. There was a 6-month follow-up period during which clinical outcomes were monitored. The incidence of the composite endpoint (23.1% vs 13.9%, P = .041) and bleeding events (6.5% vs 1.5%, P = .027) in the ticagrelor group were significantly higher compared to the clopidogrel group. Multivariate logistic regression analysis revealed that age (P = .006), hypertension (P = .007), liver insufficiency (P = .022), previous MI (P = .014) and ticagrelor (P = .044) were independent risk factors that affect the efficacy outcome. Age (P = .027) and ticagrelor (P = .016) were the independent risk factors for the safety outcome. Furthermore, in Cox survival regression analysis model, the survival rate of the efficacy endpoint in the clopidogrel group was seemingly higher than in the ticagrelor group (HR = 1.68, 95% CI: 0.97-2.90, P = .065). The survival rate of the bleeding endpoint in the clopidogrel group was higher than in the ticagrelor group (HR = 2.00, 95% CI: 1.17-3.40, P = .011). Compared to clopidogrel, ticagrelor showed increased risk of efficacy outcome and major bleeding events during 6-month follow-up in patients with ACS and LV dysfunction undergoing PCI.

OBJECTIVE: To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months.
METHODS: An open-label, multicentre, non-randomised clinical trial.
METHODS: Eight secondary and tertiary care hospitals (public and private) in Puerto Rico.
METHODS: 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases.
METHODS: Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3-5 days after PCI. Adherence medication score was also measured.
METHODS: The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models.
RESULTS: The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001).
CONCLUSIONS: The potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups.
BACKGROUND: NCT03419325.

OBJECTIVE: Antiplatelet therapy is used for the primary and secondary prevention of thrombotic diseases such as acute coronary syndrome (ACS). These patients are more vulnerable to infections, as such, strategies are required to mitigate these risks.
METHODS: We conducted a retrospective cohort study using TriNetX, a global federated health research network that includes both inpatient and outpatient electronic medical records from health care organizations worldwide. Patients ≥18 years old, after ACS, who were placed on aspirin and ticagrelor were compared with patients placed on aspirin and clopidogrel or prasugrel. Patients were identified using International Statistical Classification of Diseases and Related Health Problems terminology codes. After propensity score matching (1:1), a total of 239,358 patients were identified in each cohort. The primary outcomes of interest investigated were rates of (1) acute and subacute infective endocarditis, (2) sepsis of unknown origin, (3) staphylococcus arthritis, (4) cellulitis and acute lymphangitis, (5) Staphylococcus aureus bacteremia, and (6) staphylococcal pneumonia after initiation of treatment. Outcomes were analyzed at 1, 3, and 5 years.
RESULTS: At 5 years, a combination of aspirin and ticagrelor, compared with a combination of aspirin and clopidogrel or prasugrel, was associated with significantly reduced rates of (1) acute and subacute endocarditis (hazard ratio [HR] plus 95% CI) (HR = 0.85; 0.77-0.945; P = 0.030), (2) sepsis of unknown origin (HR = 0.89; 95% CI, 0.86-0.91; P < 0.0001), (3) cellulitis and acute lymphangitis (HR = 0.89; 95% CI, 0.87-0.92; P < 0.0001, and (4) Staphylococcus aureus bacteremia (HR = 0.72; 95% CI, 0.61-0.85; P = 0.0007). However, a combination of aspirin and clopidogrel was associated with a marinally lower risk of staphylococcal pneumonia (HR = 1.04; 95% CI, 1.01-1.062; P < 0.0001).
CONCLUSIONS: A combination of aspirin and ticagrelor is associated with a lower rate of a variety of bacterial infections. This combination warrants further investigation in in-vitro studies to tease out mechanisms and through clinical randomized trials in groups who have ACS and are at high infection risk.

BACKGROUND: This study aimed to explore the effect of a P2Y12 inhibitor regimen on the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft surgery in carriers with the cytochrome P450 family 2 subfamily C member19 loss-of-function allele.
RESULTS: From May 2019 to November 2023, patients containing the cytochrome P450 family 2 subfamily C member19*2 or *3 allele undergoing elective first-time off-pump coronary artery bypass graft surgery including aspirin 100 mg/d and ticagrelor 180 mg/d (AT group; n=95) versus clopidogrel 75 mg/d (aspirin and clopidogrel group; n=95) were prospectively followed. The primary end point was the cumulative incidence of POAF in a week. The secondary end points were POAF burden, platelet aggregability, systemic immune-inflammation index and heart rate variability. The incidence of POAF was 21.1% in the AT group versus 41.1% in the aspirin and clopidogrel group (hazard ratio, 0.46 [95% CI, 0.27-0.76]; P=0.003). POAF burden, ADP-induced platelet aggregation and systemic immune-inflammation index was notably lower in the AT group than the aspirin and clopidogrel group. Heart rate variability data showed an increase in both high-frequency and SD of normal-to-normal RR intervals in the AT group with a decreased low-frequency/high-frequency ratio, suggesting that the sympathetic/parasympathetic activation was balanced.
CONCLUSIONS: In patients carrying the cytochrome P450 family 2 subfamily C member19 loss-of-function allele, an AT regimen after off-pump coronary artery bypass grafting was associated with a lower incidence of POAF, paralleled by lower atrial fibrillation burden, ADP-induced platelet aggregation, lower systemic immune-inflammation index reaction, and a balanced automatic nerve system compared with an aspirin and clopidogrel regimen. Inhibiting the systemic immune-inflammation response and sustaining automatic nerve balance may underlie the therapeutic effect of POAF by a potent antiplatelet combination.

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UNASSIGNED: The PLATO trial data set reported to the FDA (DRFDA) revealed that some primary deaths causes (PDC) were inaccurately reported favoring ticagrelor. Trial Investigators (DRTI) received different data set with more ticagrelor mortality advantage. We compared these two death lists for the match in PDC.
UNASSIGNED: The DRFDA contains 938 deaths, while the DRTI contains 905. We matched \"vascular\", \"non-vascular\", \"unknown\", \"missed\", and \"other\" causes of death between DRFDA and DRTI. The DRFDA used 14 vascular, 9 non-vascular, 1 unknown and 1 other PDC codes, while the DRTI used 14 but different vascular, 14 non-vascular but no unknown or other PDC codes. We observed a significant mismatch for the PDC codes between the DRFDA and DRTI data sets. Most DRFDA deaths were vascular (n = 677), fewer non-vascular (n = 159) and unexpectedly many unknown (n = 95) or other (n = 7) PDC. Surprisingly, the shorter DRTI contains more vascular (n = 795), fewer non-vascular (n = 110), but no unknown, other, or missed causes. There were more sudden deaths in DRTI than in DRFDA (161 vs. 138; p < 0.03), twice as many post-myocardial infarction deaths (373 vs. 178; p < 0.001) but fewer heart failure deaths (73 vs. 109; p = 0.02). The reported non-vascular PDC match better except for 2 extra suicides in the clopidogrel arm of the DRTI.
UNASSIGNED: Over 100 \"unknown\", \"missed\", or \"other\" PDC events reported by the trial sponsor to the FDA were omitted from the investigator data set contributing to the inflated differences in vascular mortality benefit of ticagrelor reported in numerous PLATO publications. Synchronization of PDC reporting between regulatory agencies and investigators was lacking in PLATO but remains mandatory to ensure quality for future indication-seeking trials.

OBJECTIVE: This study aimed to understand the pharmacokinetics of ticagrelor in Chinese patients with acute coronary syndrome (ACS), identify influencing factors, and inform ticagrelor treatment optimization.
METHODS: Data from 195 ACS patients, including 491 plasma ticagrelor concentration timepoints and clinical information, were analyzed using NONMEN for pharmacokinetic (PK) parameter factors. The model underwent internal validation with bootstrap methodology.
RESULTS: The PK curve of ticagrelor was well delineated using a one disposition compartment model with first-order absorption rate constant, 0.67/h. When the direct bilirubin levels and white plasma cell counts increased, female patients showed decreased glomerular filtration rate, decreased ticagrelor clearance rate, and increased exposure. When the direct bilirubin levels increased and body weight and hemoglobin decreased, rs6787801 was GG compared with AA and GA, the ticagrelor metabolite clearance rate decreased and exposure increased.
CONCLUSIONS: The study offers key insights into ticagrelor\'s dose-exposure relationship post-percutaneous coronary intervention in ACS patients, highlighting factors critical for personalized treatment strategies.

OBJECTIVE: Although dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remain challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI).
RESULTS: PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6±4.0 years, females 44%) was included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4±32.1 vs. 30.4±39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; p for non-inferiority=0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29±312.36 ng/mL vs. 579.57±351.73 ng/mL, p=0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg.
CONCLUSIONS: Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI. Clinical Trial registration: EudraCT 2019-002391-13. Clinicaltrials.gov NCT04739384.

OBJECTIVE: Remote ischemic preconditioning (RIPC) reduces periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) through various pathways, including an adenosine-triggered pathway. Ticagrelor inhibits adenosine uptake, thus may potentiate the effects of RIPC. This randomized trial tested the hypothesis that ticagrelor potentiates the effect of RIPC and reduces PMI, assessed by post-procedural troponin release.
METHODS: Patients undergoing PCI for non-ST elevation acute coronary syndromes were 1:1 randomized to ticagrelor (TG-Group) or clopidogrel (CL-Group). Within each treatment, patients were 1:1 randomized to a RIPC (RIPC-Group) or a control group (CTRL-Group). The primary endpoint was the difference between post- and pre-procedural troponin at 24 h following PCI, termed deltaTnI.
RESULTS: During a 12-month period, 138 patients were included in the study (34 in the CL-CTRL group, 34 in the TG-CTRL group, 35 in the CL-RIPC group, and 35 in the TG-CTRL group). There was a significant difference in deltaTnI between the study groups [ TG-RIPC:0.04 (0-0.16), CL-CTRL:0.10 (0.03-0.43), CLRIPC:0.11 (0.03-0.89), and TG-CTRL:0.24 (0.06-0.47); p = 0.007]. Eight patients (22.9%) in the TG-RIPC group developed type 4a myocardial infarction (MI), compared to 14 (40%) in the CL-RIPC group, 13 (38.2%) in the CL-CTRL group, and 19 (55.9%) in the TG-CTRL group (p = 0.048). A significant interaction between antiplatelet group allocation and RIPC on deltaTnI was observed [F (1,134) = 7.509; p = 0.007]. In multivariate analysis, the interaction between RIPC and ticagrelor treatment was independently associated with a lower incidence of Type 4a MI.
CONCLUSIONS: Our results demonstrate an interaction between ticagrelor and RIPC, which may potentiate the cardioprotective effects of RIPC during PCI by reducing PMI.

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