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Aims Vicagrel, a novel antiplatelet prodrug to overcome the residual high platelet reactivity of clopidogrel induced by inactive metabolism and cytochrome P450 (CYP) 2C19 polymorphisms, provides favourable antiplatelet inhibition in healthy volunteers. However, its antiplatelet effect and safety in patients with coronary artery disease (CAD) are unclear. Methods and results This was a multicentre, randomized, double-blind, triple-dummy, dose-exploring phase II trial comparing the antiplatelet activity and safety of vicagrel at different doses vs. those of clopidogrel in patients with CAD undergoing percutaneous coronary intervention (PCI). The primary endpoint was inhibition of adenosine diphosphate (ADP)-induced platelet aggregation (%IPA) after loading and maintenance doses (LD/MD) at 28 days. Safety endpoints included adverse events (AEs) and Bleeding Academic Research Consortium-defined any bleeding. Pharmacokinetic (PK) profiles and the influence of CYP2C19 polymorphisms were explored in subgroup analysis. Two hundred and seventy-nine patients diagnosed with stable CAD (51.97%), unstable angina (40.86%), and myocardial infarction (7.17%) were randomized to receive vicagrel 20/5 mg (LD/MD), 24/6 mg, or 30/7.5 mg or clopidogrel 300/75 mg in combination with aspirin. %IPAs on Day 28 were 30.19%, 35.02%, 45.61%, and 32.55% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, respectively, and were comparable across all groups (P = 0.0694). The plasma concentration of the vicagrel active metabolite M15-2 had a similar area under curve and Tmax to those of clopidogrel. There were no significant differences in AEs (4.35%, 0%, 1.45%, and 5.56% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, P = 0.6667) or any bleeding (13.04%, 14.06%, 11.59%, and 11.11% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, respectively, P = 0.95) across four groups. %IPAs and PK profiles of vicagrel did not vary significantly among different CYP2C19 metabolizers. Conclusion Vicagrel had comparable antiplatelet effect and safety to clopidogrel in patients with CAD undergoing PCI.

To assess the effectiveness and safety of bivalirudin compared with heparin monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI).Bivalirudin is recommended for periprocedural use in patients undergoing PCI who are of high bleeding risk. However, its safe and efficacious use in elderly patients, a typical high bleeding risk cohort, in real world practice is yet to be reported.In this single center, real-world observational study, 4736 consecutive elderly patients who underwent PCI were enrolled. Of these, 1240 were treated with bivalirudin and 3496 with heparin according to the periprocedural anticoagulation strategies of PCI. The primary outcome was 12-month net adverse clinical events (NACE) defined as a composite of cardiac death, myocardial infarction, stroke, revascularization, or any bleeding. Propensity score matching (PSM) was used to balance baseline characteristics between groups.After PSM, bivalirudin was found to be associated with lower rates of NACE (19.1% vs. 24.7%, p = 0.002), cardiac death (2.7% vs. 4.3%, p = 0.038), and any bleeding (10.0% vs. 12.9%, p = 0.023) compared to heparin monotherapy. No differences were found in the incidences of myocardial infarction, stroke, revascularization, stent thrombosis (0.1% vs. 0.1%, p = 1.000), and major bleedings (0.5% vs. 0.5%, p = 1.000) between the two patient groups.In this real-world observational study, periprocedural use of bivalirudin in elderly patients who underwent PCI was associated with less cardiac death and any bleeding compared to heparin monotherapy, without increased risk of stent thrombosis.

To investigate the frequency of clonal hematopoiesis of indeterminate potential (CHIP) and evaluate its impacts on outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the absence of traditional cardiovascular risk factors (CVRFs).Whole-exome sequencing was performed to detect the presence of CHIP in 183 patients underwent PCI for the treatment of ACS. The association between CHIP-related mutations and major adverse cardiac or cerebral events (MACCEs, a composite of all-cause mortality, coronary revascularization, myocardial infarction, or stroke) was analyzed in such cohort.Of 179 patients [median age, 65 years; 84 female (46.9%)] included in this analysis, CHIP-related mutations were detected in 36 (20.1%) patients. The somatic mutations most frequently occurred in the genes DNMT3A (17 mutations), TET2 (6 mutations), and ASXL1 (4 mutations). Clinical outcomes at median 635 follow-up days showed that DNMT3A/TET2/ASXL1-CHIP mutations were associated with significantly higher risk of MACCEs, compared with non-CHIP carriers in the CVRFs-absent ACS cohort (26.1% vs. 4.2%, log-rank P = 0.001). Multivariable regression showed that DNMT3A/TET2/ASXL1-CHIP driver mutations (HR 4.015; 95% CI 1.236-13.046; P = 0.021) were independent predictors of adverse clinical outcomes.The most frequent CHIP-related mutations, DNMT3A, TET2, and ASXL1 are significantly associated with increased risk of recurrent cardiovascular events. Our study may be valuable target to reduce residual risk in patients with ACS carrying specific mutations.

This study evaluated clinical outcomes of switching from clopidogrel to ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). The clinical benefit of in-hospital switching from clopidogrel to ticagrelor in these patients remains unclear. Among patients with ACS initially receiving clopidogrel, logistic regression was used to identify independent predictors of switching to ticagrelor. Multivariable Cox regression was used to compare efficacy and safety between switching to ticagrelor and continuing clopidogrel. The primary endpoint was net adverse clinical events (NACEs) at 12 months, a composite of major adverse cardiovascular events (MACE) and Bleeding Academic Research Consortium (BARC) type 2/3/5 bleeding. Among 10,519 patients initially receiving clopidogrel, 1405 (13.4%) were switched to ticagrelor at discharge. Stent number, left main artery lesions, diabetes, male sex, age, estimated glomerular filtration rate of45 ml/min/1.73 m

To evaluate the effectiveness and safety of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) undergoing complex percutaneous coronary intervention (PCI).It remains inconclusive whether ticagrelor is superior to clopidogrel in ACS patients undergoing complex PCI in real-world practice.Based on an all-comers PCI registry, we compared the long-term effectiveness and safety between ticagrelor and clopidogrel in ACS patients undergoing complex PCI, defined as PCI procedures for complex lesions including bifurcation, chronic total occlusion, ostial, tortuous, calcific, diffused, thrombus-containing, and restenotic lesions. The primary ischemic outcome was a composite of cardiac death, myocardial infarction, or stroke. The safety outcome comprised Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding. Propensity score matching (PSM) was performed to reduce bias.Among ACS patients who underwent complex PCI, 4373 (35.2%) and 8065 (64.8%) received dual antiplatelet therapy based on ticagrelor and clopidogrel, respectively. The incidences of composite ischemic events (before PSM: 1.74% vs. 2.84%; after PSM: 1.50% vs. 2.65%; p 0.01 for both) and all-cause death (before PSM: 1.23% vs. 2.12%, p 0.01; after PSM: 1.09% vs. 1.81%, p = 0.02) were significantly lower in the ticagrelor-treated than in the clopidogrel-treated group. There was no significant difference in BARC types 2, 3, and 5 bleeding between groups.Whilst the risk of major bleeding was comparable between the two drugs, ticagrelor was associated with a significantly lower risk of ischemic events than clopidogrel in ACS patients undergoing complex PCI.

OBJECTIVES To evaluate the impact of extended dual antiplatelet therapy (DAPT) beyond 12 months in acute coronary syndrome (ACS) patients with intermediate-risk to high-risk of developing ischemia according to the Global Acute Coronary Event Registration (GRACE) score. BACKGROUND The duration of optimal DAPT remains controversial in patients at higher risk of developing ischemia. METHODS Overall, 9,309 ACS patients in the Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD) study were stratified as low-risk ( n = 5,112) or intermediate-risk to high-risk (n = 4,197) according to the GRACE score on hospital discharge. Clinical outcomes at 12-24 months in patients with intermediate-to-high risk who completed 1-year DAPT without any adverse events were analyzed. The primary endpoint was 24-month net adverse clinical events (NACEs). RESULTS Patients at intermediate-to-high-risk had significantly higher incidence of NACE (10.2 vs. 4.9%, p