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.

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.

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.

Outcomes of paclitaxel-coated balloon angioplasty for in-stent calcified nodule: An optical coherence tomography study.

BACKGROUND: Paclitaxel-coated balloon (PCB) angioplasty emerges as an effective therapeutic option for in-stent restenosis (ISR). However, whether PCB angioplasty would be effective for in-stent calcified nodule (ISCN) lesions remain fully understood. This study aimed to evaluate the frequency and outcomes of ISCN in patients undergoing PCB angioplasty for ISR after second-generation drug-eluting stents (G2-DES) implantation. METHODS: This study enrolled 179 lesions (160 patients) undergoing PCB angioplasty for G2-DES restenosis with optical coherence tomography guidance. According to the presence of ISCN at the minimum lumen area, the lesions were divided into two groups: the ISCN (n = 16) and the non-ISCN groups (n = 163). The primary study endpoint was the cumulative 3-year incidence of target lesion failure (TLF; a composite of cardiac death, clinically driven target vessel revascularization, and definite stent thrombosis) on a lesion basis. RESULTS: ISCN was observed in 16 of 179 lesions (8.9%). Cumulative 3-year incidence of TLF was significantly higher in the ISCN group than in the non-CN group (85.3% vs. 16.9%, inverse probability weighted hazard ratio [HR] 4.46, 95% confidence intervals [CIs]: 2.42-8.22, p < 0.001). Risk factors associated with TLF were ISCN (HR 4.55, 95% CI: 1.56-13.3, p = 0.005), recurrent ISR (HR 2.82, 95% CI: 1.50-3.30, p = 0.001), and early ISR (HR 2.18, 95% CI: 1.21-3.92, p = 0.009). CONCLUSION: ISCN was observed in 8.3% of G2-DES restenosis. PCB angioplasty had little effect on ISCN lesions compared with non-ISCN lesions, suggesting the need for careful clinical follow-up of patients with ISCN lesions after PCB angioplasty.

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.

Clinical impact of calcified nodule in patients with heavily calcified lesions requiring rotational atherectomy.

OBJECTIVES: We sought to evaluate the incidence and clinical impact of calcified nodule (CN) in patients with heavily calcified lesions requiring rotational atherectomy (RA). BACKGROUND: It remains unclear whether CN impacts adversely on clinical outcomes in patients with heavily calcified lesions. METHODS: Between January 2011 and February 2014, 264 patients after second-generation drug-eluting stent (DES) implantation following RA were retrospectively enrolled. CN was defined as a convex shape of the luminal side of calcium as assessed by intravascular ultrasound. The primary endpoint was the cumulative 5-year incidence of major adverse cardiac events (MACE), defined as a composite of cardiac death, clinically driven target lesion revascularization (CDTLR), and definite stent thrombosis (ST). RESULTS: CN was observed in 128 patients (48.5%) with heavily calcified lesions. Cumulative 5-year incidence of MACE was significantly higher in the CN group than in the non-CN group, mainly driven by a higher rate of CDTLR and ST (35.4% vs. 18.8%, p < .001; 23.2% vs. 7.9%, p < .001; 7.0% vs. 0.93%, p = .009, respectively). Independent risk factors of 5-year MACE included hemodialysis (hazard ratio [HR] = 3.39, 95% confidence intervals [CI]: 2.00-5.73, p < .001), CN (HR = 2.53, 95% CI: 1.49-4.27, p < .001), ostial lesion (HR = 3.02, 95% CI: 1.58-5.78, p = .001), left ventricular ejection fraction ≤40% (HR = 2.17, 95% CI: 1.27-3.70, p = .005), and right coronary artery lesion (HR = 1.82, 95% CI: 1.07-3.11, p = .03). CONCLUSIONS: CN was observed in 48.5% of heavily calcified lesions, resulting in unfavorable long-term clinical outcomes after second-generation DES implantation following RA.

Clinical Outcomes After Percutaneous Coronary Intervention in Patients With Cancer.

BACKGROUND: The aim of this study is to evaluate clinical outcomes after percutaneous coronary intervention (PCI) in patients with cancer.Methods and Results:Cancer screening was recommended before PCI in consecutive 1,303 patients who underwent their first PCI. By using cancer screening, cancer was diagnosed in 29 patients (2.2%). In total, 185 patients had present or a history of cancer. Patients with cancer more often suffered from non-cardiac death than those without (4.4% vs. 1.5%, P=0.006), and patients with cancer requiring ongoing therapy (n=18) more often suffered from major bleeding compared with those with recently (≤12 months) diagnosed cancer who do not have ongoing therapy (n=59) (16.7% vs. 3.4%, P=0.049). During the 1-year follow up, 25 patients (2.0%) were diagnosed as having cancer, in which 48.0% of bleeding events led to a cancer diagnosis. Patients with high bleeding risk according to the Academic Research Consortium for high bleeding risk (ARC-HBR) were associated with a greater 1-year major bleeding risk than those without high bleeding risk in patients with (7.9% vs. 0.0%, P=0.02) and without cancer (7.1% vs. 2.5%, P<0.001), respectively. CONCLUSIONS: Cancer was diagnosed in 2.2% of 1,303 unselected patients before PCI by cancer screening and in 2.0% within 1-year after PCI. Cancer was associated with a greater risk of non-cardiac death, whereas ongoing active cancer was associated with greater risk of major bleeding. ARC-HBR criteria successfully identified high-bleeding risk patients, irrespective of the presence or absence of cancer.

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.

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial.

Importance: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. Objective: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. Interventions: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. Results: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, -1.34% [95% CI, -2.57% to -0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, -0.55% [95% CI, -1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, -1.13% [95% CI, -1.84% to -0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). Conclusions and Relevance: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02619760.

Five-Year Clinical Outcomes After Drug-Eluting Stent Implantation Following Rotational Atherectomy for Heavily Calcified Lesions.

BACKGROUND: Percutaneous coronary intervention for heavily calcified lesions requires rotational atherectomy (RA). Long-term clinical outcomes after drug-eluting stent (DES) implantation following (RA) for heavily calcified lesions remain unclear. We assessed 5-year clinical outcomes after DES implantation following RA.Methods and Results:Between March 2006 and September 2011, 219 consecutive patients with 219 lesions treated with DES following RA, were retrospectively enrolled. The cumulative 5-year incidence of target-lesion revascularization (TLR) and definite stent thrombosis (ST) were assessed. The cumulative incidence of TLR within (≤) the first year was 18.6%. Late TLR beyond (>) 1 year continued to occur at 1.9% per year without a decrease in the rate (5-year incidence, 26.0%). The cumulative incidence of definite ST at 30 days, 1 and 5 years was 0.9%, 2.3% and 2.9%, respectively. The annual rate of definite ST beyond 1 year was 0.15%. On multivariate analysis, the significant predictor of TLR within 1 year was use of first-generation DES (hazard ratio [HR], 2.09; 95% CI: 1.10-4.03, P=0.02) and that of TLR beyond 1 year was hemodialysis (HR, 3.29; 95% CI: 1.06-10.55, P=0.04). CONCLUSIONS: Late TLR beyond 1 year continued to occur up to 5 years at a constant annual incidence, whereas very late ST was rare. Careful long-term clinical follow-up is continually needed in patients who have already received DES following RA for heavily calcified lesions.

Impact of lesion complexity on long-term vascular response to cobalt-chromium everolimus-eluting stent: five-year follow-up optical coherence tomography study.

The impact of lesion complexity on long-term vascular response to cobalt-chromium everolimus-eluting stent (CoCrEES) remains unclear. We sought to evaluate them using optical coherence tomography (OCT). A total of 47 patients with 58 lesions treated only with CoCrEES and no target-vessel events within 5 years after implantation were prospectively enrolled and underwent 5-year follow-up OCT. Quantitative parameters and qualitative characteristics of the neointima were evaluated using multilevel logistic or linear regression models with random effects at three levels: lesion, cross-section (CS), and strut. According to the lesion complexity, the lesions were classified into the two groups: the complex lesion (CL) and non-CL group. The CL was defined as having at least 1 high-risk feature such as acute coronary syndrome lesion, lesion length > 20 mm, severe calcification requiring rotational atherectomy, and chronic total occlusion at the index procedure. A total of 11,034 struts (CL, n = 6240; non-CL, n = 4794) and 1202 (CL, n = 683; non-CL, n = 519) CSs were analyzed. The percentage of uncovered and malapposed struts did not differ significantly between the CL and non-CL groups (0.90 vs. 0.54%, P = 0.78; 0.56 vs. 0.10%, P = 0.16, respectively). The incidence of neoatherosclerosis was comparable between both groups in the CS- and lesion-level analysis (3.5 vs. 4.6%, P = 0.91; 32.0 vs. 24.2%, P = 0.52, respectively). At 5 years, CoCrEES shows an excellent vascular healing and similar frequency of neoatheroslerosis in patients without target-vessel events, regardless of the lesion complexity.

Impact of total stent length after cobalt chromium everolimus-eluting stent implantation on 3-year clinical outcomes.

OBJECTIVES: The objective was to assess whether total stent length (TSL) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation was associated with long-term clinical outcomes. BACKGROUND: The impact of TSL after CoCr-EES implantation on long-term clinical outcomes remained unclear. METHODS: A total of 1,007 consecutive patients with 1,382 lesions treated only with CoCr-EES were analyzed. Patients and lesions were divided into tertile group: TSL per patient (TSL-P) (PA [8-23 mm], n = 382; PB [23-46 mm], n = 312; and PC [46-204 mm], n = 313), and TSL per lesion (TSL-L) (LA [8-18 mm], n = 486; LB [18-28 mm], n = 475; and LC [28-140 mm], n = 421). The cumulative 3-year incidence of clinically driven target-lesion revascularization (CD-TLR) and definite stent thrombosis (ST) based on TSL-P and TSL-L groupings were accessed. RESULTS: After inverse probability of weighted adjustment, the cumulative 3-year incidence of CD-TLR for the TSL-P and TSL-L were higher in the PC and LC groups than in the other groups (hazard ratio [HR] 2.92, 95% confidence intervals [CI] 1.66-5.15, P < 0.001 vs. PA; HR 2.49, 95% CI 1.47-4.20, P < 0.001 vs. PB; HR 1.94, 95% CI 1.15-3.28, P = 0.01 vs. LA; HR 2.80, 95% CI 1.73-4.54, P < 0.001 vs. LB, respectively). No significant differences in the cumulative 3-year incidence of definite ST were observed in both TSL-P and TSL-L groups. CONCLUSIONS: TSL after CoCr-EES implantation has significantly impact on CD-TLR rate through 3 years, but it is not associated with an increased incidence of definite ST. © 2016 Wiley Periodicals, Inc.

Difference of Tissue Characteristics Between Early and Late Restenosis After Second-Generation Drug-Eluting Stents Implantation　- An Optical Coherence Tomography Study.

BACKGROUND: The mechanism and time course of in-stent restenosis (ISR) after implantation of second-generation DES have not yet been fully elucidated. We sought to evaluate the differences in tissue characteristics between the different phases of ISR after second-generation DES implantation using optical coherence tomography (OCT).Methods and Results:From June 2010 to December 2015, 324 consecutive patients with 337 ISR lesions underwent OCT. Of these, we analyzed 53 lesions in 53 patients who had their first ISR after second-generation DES implantation and underwent OCT before any procedures. According to the timing of ISR, the patients were divided into the early group (within 1 year: E-ISR, n=30) and late group (beyond 1 year: L-ISR, n=23). Quantitative parameters and qualitative characteristics of the neointima were evaluated. In the minimum lumen area site analysis, the E-ISR group had more frequently homogeneous intima than the L-ISR group (26.7% vs. 4.4%, P=0.02). The frequencies of neointima with lipid-laden, thin-cap fibroatheroma, neovascularization and macrophage infiltration were significantly higher in the L-ISR group than in the E-ISR group (30.0% vs. 69.6%, P<0.01; 0.0% vs. 26.1%, p <0.01; 6.7% vs. 26.1%, P=0.049; 3.3% vs. 26.1%, P=0.01, respectively). CONCLUSIONS: Neointimal tissue characteristics differed between E-ISR and L-ISR after second-generation DES implantation. E-ISR was mainly caused by neointimal hyperplasia, whereas neoatherosclerosis was the main mechanism of L-ISR.

Post-PCI Anticoagulation with Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial.

The current guidelines for acute coronary syndrome (ACS) have discouraged the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation was not well supported by evidences. As a post-hoc analysis of the STOPDAPT-3 trial, the 30-day outcomes were compared between the two groups with and without post-PCI heparin administration among ACS patients without the use of mechanical support devices. The co-primary endpoints were the bleeding endpoint defined as the Bleeding Academic Research Consortium type 3 or 5 and the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4088 ACS patients, 2339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher in ST-elevation myocardial infarction than in the others (72.3% and 38.8%, P<0.001), and in patients with intraprocedural adverse angiographic findings than in those without (67.6% and 47.5%, P<0.001). Post-PCI heparin compared to no post-PCI heparin was associated with a significantly increased risk of bleeding endpoint (4.75% and 2.52%; adjusted HR 1.69 [95%CI 1.15-2.46], P=0.007) and a numerically increased risk of cardiovascular endpoint (3.16% and 1.72%; adjusted HR 1.56 [95%CI 0.98-2.46], P=0.06). Higher hourly dose or total doses of heparin were also associated with the higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in ACS patients. Post-PCI heparin use was associated with harm in terms of bleeding without a benefit in reducing cardiovascular events.

Prognostic significance of baseline low-density lipoprotein cholesterol in patients undergoing coronary revascularization; a report from the CREDO-Kyoto registry.

BACKGROUND: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear. METHOD: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels. RESULTS: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke. CONCLUSIONS: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization.

Impact of post-challenge hyperglycemia on clinical outcomes in Japanese patients with stable angina undergoing percutaneous coronary intervention.

BACKGROUND: Post-challenge hyperglycemia (PH) is well-established as one of risk factors for coronary artery disease. However, it remains unclear whether PH affects clinical outcomes in patients with stable angina undergoing percutaneous coronary intervention (PCI). METHODS: A total of 828 patients with stable angina undergoing PCI were retrospectively analyzed. Of these, 452 patients with previously diagnosed diabetes mellitus (DM) or fasting plasma glucose (PG) ≥126 mg/dl and HbA1c ≥6.5% were defined as known DM. The remaining 376 patients were divided into the two groups according to 2-h PG: PH (2-h PG ≥140 mg/dl, n=236) and normal glucose tolerance (NGT, 2-h PG <140 mg/dl, n=140). We assessed the rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, and clinically-driven revascularization. RESULTS: During the median follow-up of 4.3 years, the MACE rate was significantly higher in the DM and PH groups than the NGT group (39.3% vs. 20.7%, P <0.001; 31.4% vs. 20.7%, P=0.044, respectively). Compared with the NGT group, the cumulative incidence of revascularization was significantly higher in the DM group (35.1% vs. 18.5%, P <0.001) and tended to be higher in the PH group (27.1% vs. 18.5%, P=0.067). In the multivariate analysis, known DM (Hazard ratio [HR]: 2.16, 95% confidence interval (CI): 1.49-3.27, P < 0.001), PH (HR: 1.62, 95% CI: 1.07-2.53, P = 0.023), LDL-C >100 mg/dl (HR: 1.62, 95% CI: 1.26 to 2.10, P < 0.001), and previous stroke (HR: 1.47, 95% CI: 1.03-2.04, P = 0.034) were predictors of MACE. CONCLUSION: PH is associated with future cardiovascular events in patients with stable angina undergoing PCI.

Post-contrast Acute Kidney Injury After Emergent and Elective Percutaneous Coronary Intervention (from the CREDO-Kyoto PCI/CABG Registry Cohort 3).

Post-contrast acute kidney injury (PC-AKI) is a common complication after percutaneous coronary intervention (PCI). However, it is unclear whether or not the effects of PC-AKI on long-term clinical outcomes were different between emergent and elective procedures. Among patients enrolled in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort 3, we identified 10,822 patients treated using PCI (emergent PCI stratum: n = 5,022 [46%] and elective PCI stratum: n = 5,860 [54%]). PC-AKI was defined as ≥0.3 mg/100 ml absolute or 1.5-fold relative increase of serum creatinine within 72 hours after PCI. The incidence of PC-AKI was significantly higher after emergent PCI than after elective PCI (10.5% vs 3.7%, p <0.001). In the multivariable logistic regression model, emergent PCI was the strongest independent risk factor for PC-AKI in the entire study population. The excess adjusted risk of patients with PC-AKI relative to those without remained significant for all-cause death in both the emergent and elective PCI strata (hazard ratio 1.87, 95% confidence interval 1.59 to 2.21, p <0.001 and hazard ratio 1.31, 95% confidence interval 1.03 to 1.68, p = 0.03, respectively). There was a significant interaction between the PCI setting (emergent and elective) and the effect of PC-AKI on all-cause death, with a greater magnitude of effect in the emergent PCI stratum than in the elective PCI stratum (p for interaction = 0.01). In conclusion, the incidence of PC-AKI was 2.8 times higher after emergent PCI than after elective PCI. The excess mortality risk of PC-AKI relative to no PC-AKI was greater after emergent PCI than after elective PCI.