Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. METHODS: PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. FINDINGS: Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). INTERPRETATION: In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. FUNDING: The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Preventive PCI or medical therapy alone for vulnerable atherosclerotic coronary plaque: Rationale and design of the randomized, controlled PREVENT trial.

BACKGROUND: Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. METHODS: The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. RESULTS: Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. CONCLUSIONS: The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02316886. KEY POINTS: The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.

Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.

BACKGROUND: New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. OBJECTIVES: To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. METHODS: In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. RESULTS: Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). CONCLUSION: During 10-year of follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

End-of-Life Discussions and Their Timing for Patients With Cardiovascular Diseases　- From the Perspective of Bereaved Family Members.

BACKGROUND: Enhanced discussions regarding end-of-life (EOL) are crucial to provide appropriate care for seriously ill patients. However, the current status of EOL discussions, especially their timing and influencing factors, among patients with cardiovascular diseases (CVD) remains unknown.Methods and Results: We conducted a cross-sectional questionnaire survey of bereaved family members of CVD patients who died at 10 tertiary care institutes in Japan. In all, 286 bereaved family members (38.2% male; median age 66.0 [interquartile range 58.0-73.0] years) of CVD patients were enrolled; of these, 200 (69.9%) reported that their families had had EOL discussions with physicians. The major topic discussed was resuscitation (79.0%), and 21.5% discussed the place of EOL care. Most discussions were held during hospitalization of the patient (88.2%). More than half (57.1%) the discussions were initiated less than 1 month before the patient died, and 22.6% of family members felt that this timing of EOL discussions was late. Bereaved family members' perception of late EOL discussions was associated with the family members aggressive attitude towards life-prolonging treatment, less preparedness for bereavement, and less satisfaction with EOL care. CONCLUSIONS: Approximately 70% of bereaved family members of CVD patients had EOL discussions, which were often held shortly before the patient died. Further research is required to establish an ideal approach to EOL discussions at an appropriate time, which may improve the quality of EOL care.

Low-Density Lipoprotein Cholesterol Levels on Statins and Cardiovascular Event Risk in Stable Coronary Artery Disease　- An Observation From the REAL-CAD Study.

BACKGROUND: The relationship between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and cardiovascular event risk is still unclear in patients receiving the same doses of statins.Methods and Results: From the REAL-CAD study comparing high-dose (4 mg/day) with low-dose (1 mg/day) pitavastatin therapy in patients with stable coronary artery disease, 11,105 patients with acceptable statin adherence were divided into 3 groups according to the on-treatment LDL-C level at 6 months (<70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL). The primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. The adjusted risks of the LDL-C <70 mg/dL group relative to the LDL-C 70-100 mg/dL group (reference) was not significantly different for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58-1.18, P=0.32, and HR 1.25, 95% CI 0.88-1.79, P=0.22). The adjusted risk of the LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60-1.11, P=0.21), whereas it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08-5.17, P<0.001). CONCLUSIONS: A very low on-treatment LDL-C level (<70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70-100 mg/dL) in patients receiving the same doses of statins.

Sex Differences in Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD).Methods and Results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002). CONCLUSIONS: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Dual Antiplatelet Therapy Duration After Multivessel Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of data evaluating contemporary real-world dual antiplatelet therapy (DAPT) strategies after percutaneous coronary intervention (PCI).Methods and Results: In the OPTIVUS-Complex PCI study multivessel cohort enrolling 982 patients undergoing multivessel PCI, including left anterior descending coronary artery using intravascular ultrasound (IVUS), we conducted 90-day landmark analyses to compare shorter and longer DAPT. DAPT discontinuation was defined as withdrawal of P2Y12inhibitors or aspirin for at least 2 months. The prevalence of acute coronary syndrome and high bleeding risk by the Bleeding Academic Research Consortium were 14.2% and 52.5%, respectively. The cumulative incidence of DAPT discontinuation was 22.6% at 90 days, and 68.8% at 1 year. In the 90-day landmark analyses, there were no differences in the incidences of a composite of death, myocardial infarction, stroke, or any coronary revascularization (5.9% vs. 9.2%, log-rank P=0.12; adjusted hazard ratio, 0.59; 95% confidence interval, 0.32-1.08; P=0.09) and BARC type 3 or 5 bleeding (1.4% vs. 1.9%, log-rank P=0.62) between the off- and on-DAPT groups at 90 days. CONCLUSIONS: The adoption of short DAPT duration was still low in this trial conducted after the release of the STOPDAPT-2 trial results. The 1-year incidence of cardiovascular events was not different between the shorter and longer DAPT groups, suggesting no apparent benefit of prolonged DAPT in reducing cardiovascular events even in patients who undergo multivessel PCI.

Polypharmacy and Bleeding Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1-3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 [≤5 medications] 12.5%, T2 [6-7] 16.5%, and T3 [≥8] 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.08-1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12-1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 [95% CI 0.83-1.09; P=0.47] and HR 1.06 [95% CI 0.91-1.23; P=0.48], respectively). CONCLUSIONS: In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.

Comparison of the OPTIVUS-Complex PCI Multivessel Cohort With the Historical CREDO-Kyoto Registry Cohort-3.

BACKGROUND: There is a paucity of data on the effect of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with standard PCI or coronary artery bypass grafting (CABG) in patients with multivessel disease.Methods and Results: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI including the left anterior descending coronary artery using IVUS aiming to meet the prespecified criteria for optimal stent expansion. We conducted propensity score matching analyses between the OPTIVUS group and historical PCI or CABG control groups from the CREDO-Kyoto registry cohort-3 (1,565 and 899 patients) fulfilling the inclusion criteria for this study. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. In the propensity score-matched cohort (OPTIVUS vs. historical PCI control: 926 patients in each group; OPTIVUS vs. historical CABG control: 436 patients in each group), the cumulative 1-year incidence of the primary endpoint was significantly lower in the OPTIVUS group than in the historical PCI control group (10.4% vs. 23.3%; log-rank P<0.001) or the historical CABG control group (11.8% vs. 16.5%; log-rank P=0.02). CONCLUSIONS: IVUS-guided PCI targeting the OPTIVUS criteria combined with contemporary clinical practice was associated with superior clinical outcomes at 1 year compared with not only the historical PCI control, but also the historical CABG control.

Association between cancer history and second-generation drug-eluting stent thrombosis: insights from the REAL-ST registry.

BACKGROUND: Cancer-associated thrombosis is a frequent complication of cancer; however, little evidence is available regarding the association between cancer history and coronary artery stent thrombosis (ST). We aimed to investigate the relationship between cancer history and second-generation drug-eluting stent thrombosis (G2-ST). METHODS: From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 1265 patients (G2- ST cases, n = 253; controls, n = 1012) with cancer-related information available. RESULTS: The prevalence of patients with cancer history was higher (12.3% vs. 8.5%, p = 0.065), and that of currently diagnosed and currently treated cancer was significantly higher in ST cases than controls (3.6% vs. 1.4%, p = 0.021; 3.2% vs. 1.3%, p = 0.037, respectively). Multivariable logistic regression analysis revealed that cancer history was associated with late ST (odds ratio [OR]: 2.80, 95% confidence intervals [CI]: 0.92-8.55, p = 0.071) and very late ST (OR: 2.40, 95% CI: 1.02-5.65, p = 0.046), but not with early ST (OR: 1.01, 95% CI: 0.51-2.00, p = 0.97). During the median follow-up period of 872 days after the index ST events, patients with cancer history showed a higher mortality than those without, among both ST cases (hazard ratio [HR]: 1.93, 95% CI: 1.06-3.51, p = 0.031) and controls (HR: 1.93, 95% CI: 1.09-3.40, p = 0.023). CONCLUSION: A post hoc analysis of REAL-ST registry revealed that patients with G2-ST had a higher prevalence of currently diagnosed and currently treated cancer. Notably, cancer history was associated with the occurrence of late and very late ST, but not with early ST.

Thrombotic Risk Stratification and Intensive Statin Therapy for Secondary Prevention of Coronary Artery Disease　- Insights From the REAL-CAD Study.

BACKGROUND: It is unknown whether beneficial effects of higher-dose statins on cardiovascular events are different according to the thrombotic risk in patients with chronic coronary syndrome (CCS).Methods and Results: The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study is a randomized trial comparing 4 mg and 1 mg pitavastatin in patients with CCS. This study categorized 12,413 patients into 3 strata according to the CREDO-Kyoto thrombotic risk score: low-risk (N=9,434; 4 mg: N=4,742, and 1 mg: N=4,692), intermediate-risk (N=2,415; 4 mg: N=1,188, and 1 mg: N=1,227); and high-risk (N=564; 4 mg: N=269, and 1 mg: N=295). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina. Cumulative 4-year incidence of the primary endpoint was significantly higher in the high-risk stratum than in the intermediate- and low-risk strata (11.0%, 6.3%, and 4.5%, P<0.0001). In the low-risk stratum, the cumulative 4-year incidence of the primary endpoint was significantly lower in the 4 mg than in the 1 mg group (4.0% and 4.9%, P=0.02), whereas in the intermediate- and high-risk strata, it was numerically lower in the 4 mg than in the 1 mg group. There was no significant treatment-by-subgroup interaction for the primary endpoint (P-interaction=0.77). CONCLUSIONS: High-dose pitavastatin therapy compared with low-dose pitavastatin therapy was associated with a trend toward lowering the risk for cardiovascular events irrespective of the thrombotic risk in patients with CCS.

Rationale, Design, and Baseline Characteristics of the CURRENT AS Registry-2.

BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Bleeding Outcomes After Percutaneous Coronary Intervention in the Past Two Decades in Japan　- From the CREDO-Kyoto Registry Cohort-2 and Cohort-3.

BACKGROUND: Optimal intensity is unclear for P2Y12receptor blocker therapy after percutaneous coronary intervention (PCI) in real-world clinical practice.Methods and Results: From the CREDO-Kyoto Registry, the current study population consisted of 25,419 patients (Cohort-2: n=12,161 and Cohort-3: n=13,258) who underwent their first PCI. P2Y12receptor blocker therapies were reduced dose of ticlopidine (200 mg/day), and global dose of clopidogrel (75 mg/day) in 87.7% and 94.8% of patients in Cohort-2 and Cohort-3, respectively. Cumulative 3-year incidence of GUSTO moderate/severe bleeding was significantly higher in Cohort-3 than in Cohort-2 (12.1% and 9.0%, P<0.0001). After adjusting 17 demographic factors and 9 management factors potentially related to the bleeding events other than the type of P2Y12receptor blocker, the higher bleeding risk in Cohort-3 relative to Cohort-2 remained significant (hazard ratio (HR): 1.52 95% confidence interval (CI) 1.37-1.68, P<0.0001). Cohort-3 compared with Cohort-2 was not associated with lower adjusted risk for myocardial infarction/ischemic stroke (HR: 0.96, 95% CI: 0.87-1.06, P=0.44). CONCLUSIONS: In this historical comparative study, Cohort-3 compared with Cohort-2 was associated with excess bleeding risk, which might be at least partly explained by the difference in P2Y12receptor blockers.

Ischemic and bleeding risk after complex percutaneous coronary intervention in patients with or without high bleeding risk.

OBJECTIVES: To evaluate utility of the complex percutaneous coronary intervention (PCI) criteria in real-world practice. BACKGROUND: Applicability of procedural complexity criteria for risk stratification has not been adequately evaluated in real-world practice. METHODS: Among 13,087 patients undergoing first PCI in the CREDO-Kyoto registry cohort-2, the study population consisted of 7,871 patients after excluding patients with acute myocardial infarction and those without stent implantation. Complex PCI was defined as PCI, which fulfills at least one of the followings: three vessels treated, > = 3 stents implanted, > = 3 lesions treated, bifurcation with two stents, >60 mm total stent lengths, and target of chronic total occlusion. RESULTS: The cumulative incidences of and adjusted risks for the primary ischemic (myocardial infarction/ischemic stroke), and bleeding (GUSTO moderate/severe) endpoints were significantly higher in patients with complex PCI (N = 2,777 [35%]) than in those with noncomplex PCI (N = 5,094 [65%]) (15.4% vs. 10.9%, log-rank p < .001; odds ratio (OR): 1.53, 95% confidence interval (CI): 1.31-1.79, p < .001, and 11.9% vs. 9.9%, log-rank p = .004; OR: 1.24, 95% CI: 1.05-1.46, p = .01). In the 30-day landmark analysis, the higher risks of patients with complex PCI for ischemic and major bleeding events were only seen within 30 days after PCI (ischemic; within 30 days: HR: 2.19, 95% CI: 1.79-2.69, p < .001; beyond 30 days: HR: 1.11, 95% CI: 0.92-1.34, p = .26, and bleeding; within 30 days: HR: 1.56, 95% CI: 1.13-2.16, p = .007; beyond 30 days: HR: 1.11, 95% CI: 0.94-1.31, p = .22). CONCLUSIONS: Patients with complex PCI as compared with patients with noncomplex PCI had a higher risk for both ischemic and bleeding events mainly within 30 days after PCI.

Effects of Acute Coronary Syndrome and Stable Coronary Artery Disease on Bleeding and Ischemic Risk After Percutaneous Coronary Intervention.

BACKGROUND: Data evaluating the effects of acute coronary syndrome (ACS) relative to stable coronary artery disease (CAD) on bleeding risk after percutaneous coronary intervention (PCI) are scarce.Methods and Results:From the CREDO-Kyoto Registry Cohort-3, 13,258 patients undergoing first PCI (5,521 ACS; 7,737 stable CAD) were identified. Patients were further stratified according to ACS presentation and Academic Research Consortium High Bleeding Risk (HBR): ACS/HBR: n=2,502; ACS/no-HBR: n=3,019; stable CAD/HBR: n=3,905; and stable CAD/no-HBR: n=3,832. The primary bleeding endpoint was Bleeding Academic Research Consortium 3/5 bleeding, whereas the primary ischemic endpoint was myocardial infarction (MI)/ischemic stroke. Compared with stable CAD, ACS was associated with a significantly higher adjusted risk for bleeding (hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.68-2.03; P<0.0001), with a markedly higher risk within 30 days (HR 4.24; 95% CI 3.56-5.06; P<0.0001). Compared with the stable CAD/no-HBR group, the ACS/HBR, no-ACS/HBR, and ACS/no-HBR groups were associated with significantly higher adjusted risks for bleeding, with HRs of 3.05 (95% CI 2.64-3.54; P<0.0001), 1.89 (95% CI 1.66-2.15; P<0.0001), and 1.69 (95% CI 1.45-1.98; P<0.0001), respectively. There was no excess adjusted risk of the ACS relative to stable CAD group for MI/ischemic stroke (HR 1.07; 95% CI 0.94-1.22; P=0.33). CONCLUSIONS: Bleeding risk after PCI depended on both ACS presentation and HBR, with a significant effect of ACS within 30 days.

Overview of the 84th Annual Scientific Meeting of the Japanese Circulation Society　- Change Practice!

Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as "The Week for JCS 2020" from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was "Change Practice!" and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.

Application of the Modified High Bleeding Risk Criteria for Japanese Patients in an All-Comers Registry of Percutaneous Coronary Intervention　- From the CREDO-Kyoto Registry Cohort-3.

BACKGROUND: The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P<0.0001). Cumulative 5-year incidence of BARC 3/5 bleeding was 25.1% in patients with ARC-HBR, and 23.1% in patients with J-HBR. Cumulative incidence of myocardial infarction or ischemic stroke was also significantly higher in the J-HBR group than in the no-HBR group (6.9% vs. 3.6% at 1 year; 13.2% vs. 7.1% at 5 years, P<0.0001). CONCLUSIONS: The J-HBR criteria successfully identified those patients with very high bleeding risk after PCI, who represented 64% of patients in this all-comers registry.

Long-Term Impact of Diabetes Mellitus on Initially Conservatively Managed Patients With Severe Aortic Stenosis.

BACKGROUND: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3,815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome. CONCLUSIONS: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes.

Clinical characteristics and outcomes of patients with venous thromboembolism according to diagnosis on weekends versus on weekdays.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P < 0.001), and with more severe hemodynamic condition for PE patients. The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the two groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P = 0.87), as well as among DVT patients (0.0% vs. 1.5%, P = 0.24). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30-day were not significantly different between the 2 groups among PE patients, nor among DVT only patients. In conclusion, the VTE patients diagnosed on weekends presented more often with PE, and with more severe condition for PE patients. Nevertheless, the risk for 30-day mortality was not significantly different between patients diagnosed on weekends and on weekdays.