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Background and Aims: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS., Methods: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year., Results: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome., Conclusions: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT., Study Registration: PROSPERO (ID: CRD42023476470)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although P2Y12 inhibitor monotherapy has emerged as a promising alternative for dual antiplatelet therapy (DAPT), there remains concern regarding the safety of clopidogrel monotherapy., Aims: We sought to investigate clinical outcomes of clopidogrel monotherapy in patients with and without on-treatment high platelet reactivity (HPR)., Methods: In the SMART-CHOICE study, three-month DAPT followed by P2Y12 inhibitor monotherapy was compared with 12-month DAPT in patients undergoing percutaneous coronary intervention. A platelet function test was performed for 833 patients with clopidogrel-based therapy. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE: a composite of all-cause death, myocardial infarction, or stroke) at 12 months., Results: Overall, 108 (13.0%) patients had HPR on clopidogrel. Patients with HPR had a significantly higher rate of MACCE than patients without HPR (8.7% vs 1.5%, adjusted HR 3.036, 95% CI: 1.060-8.693, p=0.038). The treatment effect of clopidogrel monotherapy for the 12-month MACCE was not significantly different compared with DAPT among patients with HPR (8.0% vs 9.4%, adjusted HR 0.718, 95% CI: 0.189-2.737, p=0.628) and without HPR (2.2% vs 0.9%, adjusted HR 2.587, 95% CI: 0.684-9.779, p=0.161; adjusted p for interaction=0.170)., Conclusions: Clopidogrel monotherapy showed treatment effects comparable to DAPT for MACCE in patients with or without HPR. However, HPR was significantly associated with an increased risk of MACCE in clopidogrel-treated patients regardless of maintenance of aspirin., Clinical Trial Registration: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy After DES (SMART-CHOICE) (ClinicalTrials.gov: NCT02079194).

A 65-year-old man developed 3-vessel stent thrombosis after percutaneous coronary intervention with aspirin and clopidogrel. Platelet tests revealed clopidogrel resistance, which resolved after changing clopidogrel to ticagrelor. Although routine platelet tests after stenting are not recommended, these tests may be considered to identify the cause of stent thrombosis and modify antiplatelet therapy., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Importance: Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively evaluated in patients with acute coronary syndromes (ACS)., Objective: To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents., Design, Setting, and Participants: A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019., Interventions: Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529)., Main Outcomes and Measures: The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events., Results: Among 3056 patients who were randomized (mean age, 61 years; 628 women [20%]; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, -1.98% [95% CI, -3.50% to -0.45%]; hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.92]; P = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 [95% CI, 0.34 to 0.91]; P = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 [95% CI, 0.45 to 1.06]; P = .09)., Conclusions and Relevance: Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial., Trial Registration: ClinicalTrials.gov Identifier: NCT02494895.

Importance: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited., Objective: To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI., Design, Setting, and Participants: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018., Interventions: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498)., Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%., Results: Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02)., Conclusions and Relevance: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations., Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.

Objectives: This study evaluated the relationship between platelet reactivity and plaque morphology using grayscale and radiofrequency intravascular ultrasound (IVUS) virtual histology (VH)., Background: Recent studies have reported that high on-treatment platelet reactivity (HPR) is associated with higher plaque volume and the presence of multivessel disease; however, the association between HPR and plaque morphology has not been evaluated., Methods: The ADAPT-DES (Dual AntiPlatelet Therapy With Drug Eluting Stents) intravascular ultrasound substudy was a prospective, multicenter, observational study of 8,582 patients undergoing percutaneous coronary intervention with drug-eluting stents in whom platelet reactivity on clopidogrel was assessed routinely. The current analysis included 909 culprit lesions from 773 patients with pre-intervention grayscale IVUS and IVUS-VH. HPR was defined as platelet reactivity >208 P2Y12 reaction unit in point-of-care P2Y12 testing by the VerifyNow assay, measured during steady-state platelet inhibition in patients receiving an antiplatelet agent., Results: HPR was associated with 3-vessel coronary artery disease (31.0% vs. 24.4%; p = 0.04). The incidence of fibroatheroma was higher in patients with HPR than those without HPR (77.1% vs. 68.9%; p = 0.01). The HPR group had larger percent plaque and media volume (plaque and media/external elastic membrane volume: 58.1% [95% confidence interval (CI): 57.1% to 59.0%] vs. 56.6% [95% CI: 55.8% to 57.5%]; p = 0.03) and plaque burden at the minimum lumen site (76.7% [95% CI: 75.7% to 77.8%] vs. 75.0% [95% CI: 74.0% to 76.0%]; p = 0.02). Despite a similar prevalence of attenuated plaque, patients with HPR had longer culprit lesion attenuated plaque length (8.0 [95% CI: 7.0 to 9.1] mm vs. 6.5 [95% CI: 5.9 to 7.1] mm; p = 0.01). On multivariate analysis, the presence of angiographic calcium (odds ratio [OR]: 1.85: 95% CI: 1.33 to 2.56; p = 0.0002) and HPR (OR: 1.45; 95% CI: 1.05 to 2.01; p = 0.02) were independent predictors for a culprit lesion fibroatheroma., Conclusions: HPR was associated with increased culprit lesion atherosclerotic burden and adverse plaque morphology among patients undergoing percutaneous coronary intervention. Platelet reactivity might be associated with not only blood clot formation, but also severity of atherosclerosis. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Clopidogrel is used with aspirin as a standard combined treatment in patients with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel use alone. Therefore, the aim of the present study was to evaluate the effects of omeprazole, a PPI, on the antiplatelet effect of clopidogrel.We divided 20 healthy volunteers into 2 groups (n = 10 each). Twenty-four hours after a 300 mg loading dose of clopidogrel, one group received a dosage of 75 mg/day of clopidogrel and a placebo for 14 days, followed 3 weeks later by the same protocol but with coadministration of 75 mg/day clopidogrel and 20 mg/day omeprazole instead. The other group received the same treatment but in reverse order. Antiplatelet activity was assessed in terms of the P2Y12 reaction unit (PRU) and percentage inhibition using a VerifyNow P2Y12 assay system.The PRU of the omeprazole-treated subjects was significantly higher than that of the omeprazole-untreated subjects on day 14 (281.3 +/- 54.0 versus 240.0 +/- 72.2, P = 0.048). The percentage inhibition showed a decrease after the 14-day omeprazole treatment (22.7 +/- 29.9% versus 35.1 +/- 18.7%, P = 0.014). Consequently, omeprazole reduces the antiplatelet effect of clopidogrel, suggesting that careful treatment planning is required when administering omeprazole to patients on clopidogrel therapy.

Background: Platelet activation and aggregation with resultant arterial thrombus formation play a pivotal role in the pathophysiology of acute coronary syndrome (ACS). In the present study the efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, combined with heparin or low-molecular-weight heparin (dalteparin), was evaluated for the management of ACS., Methods and Results: One hundred and sixty patients (60.9+/-11.1 years, 104 male) with unstable angina or non-ST elevation myocardial infarction and who had ST-T changes and elevated troponin were randomly assigned to 4 groups: group I (n=40: heparin alone), group II (n=40: dalteparin alone), group III (n=40: tirofiban + heparin) and group IV (n=40: tirofiban + dalteparin). The occurrence of major adverse cardiac events (MACE) was compared prospectively during a 6-month clinical follow-up. Percutaneous coronary intervention or coronary artery bypass graft was performed in 32 cases in group I, 29 in group II, 28 in group III and 31 in group IV (p=0.72). Minor bleeding complication developed in 2 patients (5.0%) in group I, 2 (5.0%) in group II, 4 (10.0%) in group III and 3 (7.5%) in group IV (p=0.78). During the follow-up MACE occurred in 10 patients (31.3%) in group I, 9 (31.0%) in group II, 4 (14.3%) in group III and 4 (12.9%) in group IV (p=0.02: Group I and II vs Group III and IV)., Conclusions: Tirofiban combined with dalteparin was associated with relatively more bleeding complications in the short term, but was effective in reducing the incidence of MACE during long-term clinical follow-up in patients with ACS.