An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

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.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Prevalence and Effects of High-Intensity Statins for Japanese Patients Presenting With Acute Coronary Syndrome　- A Post Hoc Secondary Analysis of STOPDAPT-2 ACS.

BACKGROUND: The REAL-CAD trial, reported in 2017, demonstrated a significant reduction in cardiovascular events with high-intensity statins in patients with chronic coronary syndrome. However, data are scarce on the use of high-intensity statins in Japanese patients with acute coronary syndrome (ACS).Methods and Results: In STOPDAPT-2 ACS, which exclusively enrolled ACS patients between March 2018 and June 2020, 1,321 (44.2%) patients received high-intensity statins at discharge, whereas of the remaining 1,667 patients, 96.0% were treated with low-dose statins. High-intensity statins were defined as the maximum approved doses of strong statins in Japan. The incidence of the cardiovascular composite endpoint (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke) was significantly lower in patients with than without high-intensity statins (1.44% vs. 2.69% [log-rank P=0.025]; adjusted hazard ratio [aHR] 0.48, 95% confidence interval [CI] 0.24-0.94, P=0.03) and the effect was evident beyond 60 days after the index percutaneous coronary intervention (log-rank P=0.01; aHR 0.38, 95% CI 0.17-0.86, P=0.02). As for the bleeding endpoint, there was no significant difference between the 2 groups (0.99% vs. 0.73% [log-rank P=0.43]; aHR 0.96, 95% CI 0.35-2.60, P=0.93). CONCLUSIONS: The prevalence of high-intensity statins has increased substantially in Japan. The use of the higher doses of statins in ACS patients recommended in the guidelines was associated with a significantly lower risk of the primary cardiovascular composite endpoint compared with lower-dose statins.

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.

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.

Dexmedetomidine versus haloperidol for sedation of non-intubated patients with hyperactive delirium during the night in a high dependency unit: study protocol for an open-label, parallel-group, randomized controlled trial (DEX-HD trial).

BACKGROUND: Delirium is common in critically ill patients. Haloperidol has long been used for the treatment of delirium. Dexmedetomidine has recently been used to treat delirium among intubated critically ill patients. However, the efficacy of dexmedetomidine for delirium in non-intubated critically ill patients remains unknown. We hypothesize that dexmedetomidine is superior to haloperidol for sedation of patients with hyperactive delirium, and would reduce the prevalence of delirium among non-intubated patients after administration. We will conduct a randomized controlled trial to compare dexmedetomidine and haloperidol for the treatment of nocturnal hyperactive delirium in non-intubated patients in high dependency units (HDUs). METHODS: This is an open-label, parallel-group, randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for nocturnal hyperactive delirium in non-intubated patients at two HDUs of a tertiary hospital. We will recruit consecutive non-intubated patients who are admitted to the HDU from the emergency room, and allocate them in a 1:1 ratio to the dexmedetomidine or haloperidol group in advance. The allocated investigational drug will be administered only when participants develop hyperactive delirium (Richmond Agitation-Sedation Scale [RASS] score ≥1 and a positive score on the Confusion Assessment Method for the ICU between 19:00 and 6:00 the next day) during the night at an HDU. Dexmedetomidine is administered continuously, while haloperidol is administered intermittently. The primary outcome is the proportion of participants who achieve the targeted sedation level (RASS score of between -3 and 0) 2h after the administration of the investigational drug. Secondary outcomes include the sedation level and prevalence of delirium on the day following the administration of the investigational drugs, and safety. We plan to enroll 100 participants who develop nocturnal hyperactive delirium and receive one of the two investigational drugs. DISCUSSION: This is the first randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for sedation of non-intubated critically ill patients with hyperactive delirium in HDUs. The results of this study may confirm whether dexmedetomidine could be another option to sedate patients with hyperactive delirium. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT1051220015, registered on 21 April 2022.

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.

Percutaneous coronary intervention versus coronary arterial bypass grafting in patients with multi-vessel coronary revascularization (from the CREDO-Kyoto PCI/CABG registry/cohort-2).

OBJECTIVE: To assess long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent only compared with coronary artery bypass grafting (CABG) in patients with triple-vessel disease. BACKGROUND: Selection between PCI and CABG is still a clinically relevant issue in the management of patients with multi-vessel coronary artery disease. METHODS: Among 15,939 patients enrolled in the CREDO-Kyoto PCI/CABG registry/cohort-2, the current study population consisted of 2,193 patients who underwent elective multi-vessel coronary revascularization including left anterior descending coronary artery (LAD) either by PCI with sirolimus-eluting stent (SES) only (N = 945) or CABG (N = 1,248). RESULTS: The cumulative 5-year incidence of and the adjusted risk for the primary outcome measure (a composite of all-cause death, myocardial infarction [MI], or stroke) were not significantly different between PCI and CABG groups (22.6% vs. 23.0%, p = .40, and HR: 1.13, 95%CI: 0.91-1.40, p = .26). The risk of PCI relative to CABG for all-cause death and stroke was also insignificant (HR: 1.19, 95%CI: 0.92-1.53, p = .19; HR: 0.89, 95%CI: 0.62-1.27, p = .51). The adjusted 5-year risk for MI, hospitalization for heart failure (HF), any coronary revascularization and major bleeding was significantly different between the groups (HR: 1.59, 95%CI: 1.10-2.30, p = .01; HR: 1.49, 95%CI: 1.05-2.11, p = .02; HR: 3.70, 95%CI: 2.91-4.70, p < .0001; HR: 0.18, 95%CI: 0.14-0.22, p < .0001). CONCLUSIONS: In patients who underwent coronary revascularization for multiple vessels including LAD, PCI using SES as compared with CABG was associated with a comparable 5-year risk for death/MI/stroke as well as for mortality, but with a markedly higher risk for any coronary revascularization.

Transradial vs. Transfemoral Percutaneous Coronary Intervention in Patients With or Without High Bleeding Risk Criteria.

BACKGROUND: The transradial approach is reportedly associated with reduced bleeding complications and mortality after percutaneous coronary intervention (PCI). It is unknown whether the clinical benefits of transradial vs. transfemoral PCI differ between high bleeding risk (HBR) and non-HBR patients.Methods and Results:After excluding patients with acute myocardial infarction, dialysis, and a transbrachial approach from the 13,087 patients undergoing first PCI in the CREDO-Kyoto Registry Cohort-2, 6,828 patients were eligible for this study. Patients were divided into 2 groups according to bleeding risk based on Academic Research Consortium HBR criteria, and then divided into a further 2 groups according to access site, radial or femoral: HBR-radial, n=1,054 (38.3%); HBR-femoral, n=1,699 (61.7%); non-HBR-radial, n=1,682 (41.3%); and non-HBR-femoral, n=2,393 (58.7%). In the HBR group, the 30-day incidence and adjusted risk for major bleeding (1.9% vs. 4.7% [P<0.001]; adjusted hazard ratio [aHR] 0.44, 95% confidence interval [CI] 0.26-0.71 [P<0.001]) and all-cause death (0.3% vs. 0.9% [P=0.04]; aHR 0.30, 95% CI 0.07-0.93 [P=0.04]) were significantly lower in the radial than femoral group. There were no significant differences in the 30-day incidence and adjusted risk for major bleeding (0.5% vs. 1.0% [P=0.09]; aHR 0.68, 95% CI 0.30-1.45 [P=0.33]) or all-cause death (0.1% vs. 0.1% [P=0.96]; aHR 1.51, 95% CI 0.19-9.54 [P=0.67]) between the radial and femoral approaches in the non-HBR group. CONCLUSIONS: Compared with transfemoral PCI, transradial PCI was associated with lower risk for 30-day major bleeding and mortality in HBR but not non-HBR patients.

Clopidogrel Monotherapy vs. Aspirin Monotherapy Following Short-Term Dual Antiplatelet Therapy in Patients Receiving Everolimus-Eluting Coronary Stent Implantation.

BACKGROUND: There is a scarcity of data on short-duration dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy as compared with aspirin monotherapy after percutaneous coronary intervention (PCI).Methods and Results:STOPDAPT-1 is a prospective trial enrolling patients who agreed to 3-month DAPT followed by aspirin monotherapy after everolimus-eluting stent (EES) implantation. STOPDAPT-2 is a randomized trial comparing 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT after EES implantation. We compared the clinical outcomes of patients assigned to the 1-month DAPT group in STOPDAPT-2 and the 3-month DAPT group enrolled in STOPDAPT-1. The current study population consisted of 1,480 patients in STOPDAPT-2 and 1,339 patients in STOPDAPT-1. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis and TIMI major/minor bleeding. Cumulative 1-year incidence of the primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (2.3% vs. 2.3%, P=0.98). After adjusting for confounders, there was no excess risk of STOPDAPT-2 relative to STOPDAPT-1 for the primary endpoint. Between 3 and 12 months, the cumulative incidence of primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (1.7% vs. 1.6%, P=0.77). CONCLUSIONS: The effect of 1-month DAPT followed by clopidogrel monotherapy on clinical outcomes was similar to that of 3-month DAPT followed by aspirin monotherapy in patients receiving PCI.

Effects of Body Weight on Bleeding and Ischemic Events in Patients Undergoing Percutaneous Coronary Intervention　- From the CREDO-Kyoto Registry Cohort-2.

BACKGROUND: The effect of body weight (BW) on bleeding and ischemic events has not been adequately evaluated in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:12,690 consecutive patients undergoing first PCI in the CREDO-Kyoto registry cohort-2 were divided into 3 groups according to tertiles of BW stratified by sex (male; Tertile 1 [<60.0 kg], 2 [60.0-68.0 kg], and 3 [>68.0 kg], and female; Tertile 1 [<47.9 kg], 2 [47.9-55.8 kg], and 3 [>55.8 kg]). Cumulative 5-year incidences of the primary bleeding (GUSTO moderate/severe) and ischemic (myocardial infarction/ischemic stroke) endpoints increased incrementally with decrease in BW in both strata (male Tertiles 1, 2, and 3: 13.7%, 10.3%, and 8.0%, P<0.001, and 13.9%, 11.3%, and 10.2%, P<0.001; female Tertiles 1, 2, and 3: 17.9%, 12.9%, and 10.1%, P<0.001, and 17.9%, 12.9%, and 10.1%, P<0.001). Compared with Tertile 3, the adjusted risks of Tertile 1 for the primary bleeding and ischemic endpoints remained significant in the female stratum (hazard ratio (HR): 1.45, 95% confidence interval (CI): 1.14-1.87, P=0.003, and HR:1.49, 95% CI:1.13-1.95, P=0.004), but not in the male stratum (HR:1.10, 95% CI:0.92-1.32, P=0.31, and HR:1.06, 95% CI:0.90-1.27, P=0.47). CONCLUSIONS: Cumulative incidences of bleeding and ischemic events increased incrementally as BW decreased in both men and women. The adjusted risks of underweight relative to overweight for bleeding and ischemic events were significant only in women.

Transcatheter Aortic Valve Implantation vs. Surgical Aortic Valve Replacement for Severe Aortic Stenosis in Real-World Clinical Practice.

BACKGROUND: There are no data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) outcomes in real clinical practice in Japan. METHODS AND RESULTS: We combined 2 independent registries, the K-TAVI Registry (a 6-center prospective registry of consecutive patients who underwent TAVI) and the CURRENT AS Registry (a large, 27-center registry of 3,815 consecutive patients with severe aortic stenosis [AS]). In the K-TAVI Registry, 338 patients underwent TAVI with SAPIEN XT balloon-expandable valves from October 2013 to January 2016, whereas in the CURRENT AS Registry 237 patients with severe AS underwent SAVR from January 2003 to December 2011. Propensity score matching was conducted, with final cohort comprising 306 patients. The cumulative 2-year incidence of all-cause death and heart failure (HF) hospitalization did not differ significantly between the TAVI and SAVR groups (13.7% vs. 12.4% [P=0.81] and 7.9% vs 3.9% [P=0.13], respectively). After adjusting for residual confounders, there were no significant differences between the TAVI and SAVR groups in the risk for all-cause death (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.35-1.58; P=0.43) or HF hospitalization (HR 1.27; 95% CI 0.40-4.59; P=0.69). CONCLUSIONS: These findings from 2 independent Japanese registries suggest that the 2-year risk of all-cause mortality and HF does not differ significantly between TAVI and SAVR groups in real-world practice in Japan.