Long-term outcomes of high bleeding risk patients undergoing percutaneous coronary intervention: a Korean nationwide registry.

BACKGROUND AND AIMS: Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients. METHODS: This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events. RESULTS: Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P < .001) and ischaemic events (33.8% vs. 14.4%, P < .001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04-3.21, P < .001] and for ischaemic events (HR 2.50, 95% CI 2.45-2.56, P < .001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66-3.79, P < .001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion. CONCLUSIONS: Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients.

Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study.

BACKGROUND: Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial. METHODS: From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group). RESULTS: During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P<0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 [95% CI, 0.55-0.79]; P<0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 [95% CI, 0.57-0.94]; P=0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 [95% CI, 0.82-1.31]; P=0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period. CONCLUSIONS: During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02044250.

Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.

BACKGROUND: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology. METHODS: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding. RESULTS: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P<0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P=0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P=0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event. CONCLUSIONS: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02601157.

Renal Function-Stratified Comparison of Short- and Long-Term Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention With Third-Generation Drug-Eluting Stents　- Post Hoc Analysis From the HOST-IDEA Randomized Clinical Trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with chronic kidney disease undergoing percutaneous coronary intervention (PCI), especially with third-generation drug-eluting stents (DES), remains unknown. METHODS AND RESULTS: We conducted a prespecified post hoc analysis of the HOST-IDEA trial, randomizing patients undergoing PCI with third-generation DES to 3- to 6-month or 12-month DAPT. In all, 1,997 patients were grouped by their estimated glomerular filtration rate (eGFR): high (>90 mL/min/1.73 m2), intermediate (60-90 mL/min/1.73 m2), and low (<60 mL/min/1.73 m2). The primary outcome was net adverse clinical events (NACE), a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding (Bleeding Academic Research Consortium Type 3 or 5) at 12 months. Secondary outcomes were target lesion failure (TLF) and major bleeding. The low eGFR group had the highest rates of NACE, TLF, and major bleeding compared with the other 2 groups (P<0.001). Rates of NACE were similar in the 3- to 6-month and 12-month DAPT in the high (2.9% vs. 3.2%; P=0.84), intermediate (2.1% vs. 2.8%, P=0.51), and low (8.9% vs. 9.1%; hazard ratio 0.99; P=0.97; Pinteraction=0.88) eGFR groups. TLF and major bleeding events showed similar trends. CONCLUSIONS: In patients undergoing PCI with third-generation DES, 3- to 6-month DAPT was comparable to 12-month DAPT for clinical outcomes regardless of renal function.

Smoking and cardiovascular outcomes after percutaneous coronary intervention: a Korean study.

BACKGROUND AND AIMS: The authors investigated the impact of smoking and its cessation after percutaneous coronary intervention (PCI) on cardiovascular outcomes. METHODS: Using a nationwide database from the Korean National Health Insurance System, 74 471 patients undergoing PCI between 2009 and 2016 were classified as non-, ex-, or current smokers, depending on smoking status at the first health check-up within 1 year after PCI. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, coronary revascularization, and stroke. RESULTS: During 4.0 years of follow-up, current smokers had a 19.8% higher rate of MACCE than non-smokers [adjusted hazard ratio (aHR) 1.198; 95% confidence interval (CI) 1.137-1.263], and ex-smokers tended to have a comparable rate with that of non-smokers (aHR 1.036; 95% CI .992-1.081). For 31 887 patients with both pre- and post-PCI health check-up data, the effects of smoking cessation were analysed. Among quitters who stopped smoking after PCI, quitters with cumulative smoking exposure of <20 pack-years (PYs) tended to have a comparable rate of MACCE with that of persistent non-smokers. However, the rate in quitters with cumulative exposure of ≥20 PYs was comparable with that of persistent smokers [aHR (95% CI) for <10 PY, 1.182 (.971-1.438); 10-20 PYs 1.114 (.963-1.290); 20-30 PYs 1.206 (1.054-1.380); ≥ 30 PYs 1.227 (1.113-1.352); persistent smokers 1.223 (1.126-1.328), compared with persistent non-smokers, respectively, P for interaction <.001]. CONCLUSIONS: Smoking is associated with a higher risk of adverse outcomes in patients undergoing PCI. Quitters after PCI with <20 PYs were associated with a risk comparable with that of non-smokers.

Dual antiplatelet therapy de-escalation in acute coronary syndrome: an individual patient meta-analysis.

AIMS: Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS. METHODS AND RESULTS: Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints. CONCLUSION: In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy. STUDY REGISTRATION NUMBER: This study was registered in the PROSPERO (ID: CRD42021245477).

Efficacy and Safety of Triple Therapy of Telmisartan/Amlodipine/Rosuvastatin in Patients with Dyslipidemia and Hypertension: A Multicenter Randomized Clinical Trial.

Background: Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. Objective: This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. Methods: This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Results: Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (P = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were -16.27 (0.93) mm Hg in the TEL/ALD/RSV group, -6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = -9.42 mm Hg; 95% CI, -11.99 to -6.84; P < .001). For LDL-C level changes, a significant difference was noted between the 2 groups: -50.03% (1.18%) in the TEL/ALD/RSV group, -39.60% (1.17%) in the ALD/ATV group (LSM difference = -10.43%; 95% CI, -13.70 to -7.16; P < .001). No severe adverse events were observed. Conclusions: TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX-XXX). ClinicalTrials.gov identifier: NCT03860220.

Impact of diabetes on long-term outcomes of bifurcation percutaneous coronary intervention. An analysis from the BIFURCAT registry.

BACKGROUND: It is still unclear the impact of diabetes mellitus (DM) in complex coronary lesions treated with percutaneous coronary intervention (PCI) which themselves are at increased incidence of adverse events. METHODS: BIFURCAT registry encompassed patients treated with PCI for coronary bifurcation lesion from the COBIS III and the RAIN registry. The primary endpoint was the occurrence of major cardiovascular adverse event (MACE), a composite and mutual exclusive of all-cause death or myocardial infarction (MI) or target-lesion revascularization (TLR). A total of 5537 patients were included in the analysis and 1834 (33%) suffered from DM. RESULTS: After a median follow-up of 21 months, diabetic patients had a higher incidence of MACE (17% vs. 9%, p < 0.001), all-cause mortality (9% vs. 4%, p < 0.001), TLR (5% vs. 3%, p = 0.001), MI (4% vs. 2%, p < 0.001), and stent thrombosis (ST) (2% vs. 1%, p = 0.007). After multivariate analysis, diabetes remained significantly associated with MACE (hazard ratio [HR]: 1.37; confidence interval [CI]: 1.13-1.65; p = 0.001), all-cause death (HR: 1.65; 95% CI: 1.24-2.19, p = 0.001), TLR (HR: 1.45; CI: 1.03-2.04; p = 0.031) and ST (HR: 1.73, CI: 1.04-2.88; p = 0.036), but not with MI (HR: 1.34; CI: 0.93-1.92; p = 0.11). Among diabetics, chronic kidney disease (HR: 2.99; CI: 2.21-4.04), baseline left ventricular ejection fraction (HR: 0.98; CI: 0.97-0.99), femoral access (HR: 1.62; CI: 1.23-2.15), left main coronary artery (HR: 1.44; CI: 1.06-1.94), main branch diameter (HR: 0.79; CI: 0.66-0.94) and final kissing balloon (HR: 0.70; CI: 0.52-0.93) were independent predictors of MACE at follow-up. CONCLUSIONS: Patients with DM treated with PCI for coronary bifurcations have a worse prognosis due to higher incidence of MACE, all-cause mortality, TLR and ST compared to the non-diabetics.

Body Mass Index and Major Adverse Events During Chronic Antiplatelet Monotherapy After Percutaneous Coronary Intervention With Drug-Eluting Stents　- Results From the HOST-EXAM Trial.

BACKGROUND: This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).Methods and Results: Overall, 5,112 patients were stratified (in kg/m2) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2.183 [1.199-3.974]), but lower in the obesity (HR 0.730 [0.558-0.954]) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight (HR 4.140 [1.704-10.059]) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes. CONCLUSIONS: Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.

Real-world evidence of switching P2Y12 receptor-inhibiting therapies to prasugrel after PCI in patients with ACS: results from EFF-K registry.

BACKGROUND: Potent P2Y12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS. METHODS: The EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting). RESULTS: A total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56-2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups. CONCLUSIONS: Dual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI. TRIAL REGISTRATION: KCT0002356, registered June 13, 2017.

Durable Polymer Versus Biodegradable Polymer Drug-Eluting Stents After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome: The HOST-REDUCE-POLYTECH-ACS Trial.

BACKGROUND: Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients. METHODS: The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS. The primary end point was a patient-oriented composite outcome (a composite of all-cause death, nonfatal myocardial infarction, and any repeat revascularization) at 12 months. The key secondary end point was device-oriented composite outcome (a composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) at 12 months. RESULTS: A total of 3413 patients were randomized to receive the DP-DES (1713 patients) and BP-DES (1700 patients). At 12 months, patient-oriented composite outcome occurred in 5.2% in the DP-DES group and 6.4% in the BP-DES group (absolute risk difference, -1.2%; Pnoninferiority<0.001). The key secondary end point, device-oriented composite outcome, occurred less frequently in the DP-DES group (DP-DES vs BP-DES, 2.6% vs 3.9%; hazard ratio, 0.67 [95% CI, 0.46-0.98]; P=0.038), mostly because of a reduction in target lesion revascularization. The rate of spontaneous nonfatal myocardial infarction and stent thrombosis were extremely low, with no significant difference between the 2 groups (0.6% versus 0.8%; P=0.513 and 0.1% versus 0.4%; P=0.174, respectively). CONCLUSIONS: In ACS patients receiving percutaneous coronary intervention, DP-DES was noninferior to BP-DES with regard to patient-oriented composite outcomes at 12 months after index percutaneous coronary intervention. Registration: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT02193971.

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.

BACKGROUND: Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population. METHODS: We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250. FINDINGS: Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035). INTERPRETATION: Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events. FUNDING: ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

Angiographic complete revascularization versus incomplete revascularization in patients with diabetes mellitus.

BACKGROUND: Considering the nature of diabetes mellitus (DM) in coronary artery disease, it is unclear whether complete revascularization is beneficial or not in patients with DM. We investigated the clinical impact of angiographic complete revascularization in patients with DM. METHODS: A total of 5516 consecutive patients (2003 patients with DM) who underwent coronary stenting with 2nd generation drug-eluting stent were analyzed. Angiographic complete revascularization was defined as a residual SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score of 0. The patient-oriented composite outcome (POCO, including all-cause death, any myocardial infarction, and any revascularization) and target lesion failure (TLF) at three years were analyzed. RESULTS: Complete revascularization was associated with a reduced risk of POCO in DM population [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.52-0.93, p = 0.016], but not in non-DM population (adjusted HR 0.90, 95% CI 0.69-1.17, p = 0.423). The risk of TLF was comparable between the complete and incomplete revascularization groups in both DM (adjusted HR 0.75, 95% CI 0.49-1.16, p = 0.195) and non-DM populations (adjusted HR 1.11, 95% CI 0.75-1.63, p = 0.611). The independent predictors of POCO were incomplete revascularization, multivessel disease, left main disease and low ejection fraction in the DM population, and old age, peripheral vessel disease, and low ejection fraction in the non-DM population. CONCLUSIONS: The clinical benefit of angiographic complete revascularization is more prominent in patients with DM than those without DM after three years of follow-up. Relieving residual disease might be more critical in the DM population than the non-DM population. Trial registration The Grand Drug-Eluting Stent registry NCT03507205.

Direct Conversion of Cell Fate and Induced Endothelial Cells.

Advances in nuclear reprogramming technology have enabled the dedifferentiation and transdifferentiation of mammalian cells. Forced induction of the key transcription factors constituting a transcriptional network can convert cells back to their pluripotent status or directly to another cell fate without inducing pluripotency. To date, direct conversion to several cell types, including cardiomyocytes, various types of neurons, and pancreatic ß-cells, has been reported. We previously demonstrated direct lineage reprogramming of adult fibroblasts into induced endothelial cells (iECs) in mice and humans. In contrast to induced pluripotent stem cells, for which there is consensus on the criteria defining pluripotency, such criteria have not yet been established in the field of direct conversion. We thus suggest that careful assessment of the status of converted cells using genetic and epigenetic profiling, various functional assays, and the use of multiple readouts is essential to determine successful conversion. As direct conversion does not go through pluripotent status, this technique can be utilized for therapeutic purposes without the risk of tumorigenesis. Further, direct conversion can be induced in vivo by gene delivery to the target tissue or organ in situ. Thus, direct conversion technology can be developed into cell therapy or gene therapy for regenerative purposes. Here, we review the potential and future directions of direct cell fate conversion and iECs.

Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy. METHODS: HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971. RESULTS: From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference -2·9%, pnon-inferiority<0·0001; hazard ratio 0·70 [95% CI 0·52-0·92], pequivalence=0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40-1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32-0·73]; p=0·0007). INTERPRETATION: In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia. FUNDING: Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio.

The validation of the dual antiplatelet therapy score in East Asians receiving percutaneous coronary intervention with exclusively second generation drug-eluting stents.

OBJECTIVES: We investigated whether the dual antiplatelet therapy (DAPT) score (DS) predicts clinical outcome in an East-Asian population that received exclusively second generation drug-eluting stent (DES). BACKGROUNDS: It is uncertain whether the DS could adequately risk stratify patients exclusively receiving second generation DES. METHODS: From the Grand-DES registry, we evaluated patients who were treated with DAPT for at least 12 months and were event-free at 12 months after DES implantation. Patients were classified into two categories: high DS (≧2) (n = 3,157); and low DS (<2) (n = 5,226). The primary ischemic outcome was a composite of stent thrombosis and all myocardial infarction (MI), and the primary bleeding outcome was TIMI major or minor bleeding. A propensity score (PS)-matched analysis was done to correct for baseline differences between extended DAPT group and the conventional group. RESULTS: Among 8,383 subjects, the primary ischemic outcome occurred in 48 patients (0.6%) and the primary bleeding outcome in 49 patients (0.6%). High DS was associated with a higher incidence of ischemic events (ischemic outcome: 0.8% vs. 0.4%, for high vs. low DS, Log-rank p = .039), but not with any differences in bleeding events (Log-rank p = .734). In the PS-matched analysis, extended group was associated with lower risk of composite endpoint of MI, stent thrombosis, or cardiac death in only the high DS group (1.8% vs. 3.7%, Log-rank p = .004; hazard ratio 0.45, 95% confidence interval 0.27-0.76; p = .003 after adjustment). CONCLUSIONS: The DS was an adequate risk stratifier for future ischemic events in East Asians receiving exclusively second generation DES.

Procedural optimization of drug-coated balloons in the treatment of coronary artery disease.

OBJECTIVES: This study aimed to investigate the effects of procedural optimization on the clinical outcomes of using the drug-coated balloon (DCB) in the treatment of coronary artery disease. BACKGROUNDS: Procedural optimization is considered an essential step in DCB treatment. METHODS: Data of consecutive patients who underwent DCB treatment at the Seoul National University Hospital were collected. The primary outcome was target lesion failure (TLF) at 2 years. RESULTS: Among 259 patients (309 lesions), TLF was observed in 31 (12.0%) patients. The following were modifiable procedural factors: residual percent diameter stenosis (%DS) after lesion preparation; DCB-to-vessel/stent ratio; time-delay to inflation; and total DCB inflation time. The best cutoff values for these parameters were 20%, 0.95, 25, and 60 s, respectively. The patients were classified based on the number of procedural factors that satisfied adequate criteria. TLF was observed in 7.3% in the fully optimized group, 9.1% in the partially optimized group, and 34.1% in the nonoptimized group over 2 years (p < .001). The adequacy of the four factors for DCB optimization was an independent predictor of TLF (adjusted hazards ratio for each unmet criteria for optimization, 2.05, 95% confidence interval 1.74-2.36, p < .001). CONCLUSION: The optimization of the four procedural factors could reduce TLF following DCB treatment.

Comparison of 2-Stenting Strategies Depending on Sequence or Technique for Bifurcation Lesions in the Second-Generation Drug-Eluting Stent Era　- Analysis From the COBIS (Coronary Bifurcation Stenting) III Registry.

BACKGROUND: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis. CONCLUSIONS: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.

Time Course and Risk Factors of New-Onset Complete Atrioventricular Block After Transcatheter Aortic Valve Implantation.

In this study, we aimed to investigate the time course of new-onset complete atrioventricular block (CAVB) and its reversibility after transcatheter aortic valve implantation (TAVI). We analyzed 206 consecutive patients without baseline CAVB who underwent successful TAVI. The incidence of new-onset CAVB was determined to be 12.6% (26/206). Among these patients, 14 recovered from CAVB within 2 weeks (6.8%, 14/206), while the remaining 12 (5.8%, 12/206) underwent permanent pacemaker (PPM) insertion. Among the 12 patients who received the PPM, 4 were able to recover from CAVB within 4 months. Thus, only 8 among 206 patients (3.8%) showed persistent CAVB. Early-onset CAVB on the day of the procedure was the strongest predictor of PPM implantation (OR = 127). The electrocardiographic changes that occurred after TAVI were mostly recovered after 1 month. The most critical procedural factor that predicts CAVB and PPM insertion is the deep implantation (>4 mm) of a big valve (oversizing index >5.9%). In conclusion, the incidence of CAVB after TAVI was estimated to be at 12.6%. Two-thirds of these patients recovered from CAVB within 3 days, resulting in a final rate of persistent CAVB of 4%. To prevent CAVB, we have to implant an appropriate valve type with an optimal size and depth.

Association of Side-Branch Treatment and Patient Factors in Left Anterior Descending Artery True Bifurcation Lesions: Analysis from the GRAND-DES Pooled Registry.

METHODS: Patients undergoing PCI to left anterior descending (LAD) bifurcation lesions with contemporary DES were analyzed from a nationwide registry. Baseline risk was assessed using the Age, Creatinine, and Ejection Fraction (ACEF) score. Target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization, was assessed at 3 years. RESULTS: Among 1,089 patients with LAD bifurcation lesions, 548 (50.3%) patients underwent SB treatment. The SB treatment group showed a nonsignificant, but numerically lower rate of 3-year TLF (6.6% vs. 9.2%, HR 0.75, 95%CI 0.44-1.28, p = 0.29). In patients with low pretreatment risk (ACEF<1.22), SB treatment was associated with a lower rate of 3-year TLF (HR 0.43, 95%CI 0.19-0.96, p = 0.04), while no significant difference was observed in patients with high risk (ACEF≥1.22). The difference in the low risk group was mostly driven by target lesion revascularization (HR 0.24, 95%CI 0.08-0.75, p = 0.01). CONCLUSIONS: SB treatment for LAD bifurcation lesions showed favorable long-term outcomes compared with main-branch-only intervention, especially in patients with low pretreatment risk.