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Background: There is a scarcity of data evaluating the effect of peripheral artery disease (PAD) on long-term mortality after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in patients with severe coronary artery disease in real-world practice., Methods: Among 14,867 consecutive patients who underwent their first coronary revascularization with PCI or isolated CABG between 2011 and 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, the current study population consisted of 3380 patients with three-vessel coronary artery disease or left main coronary artery disease. Long-term clinical outcomes were compared between PCI and CABG stratified by the presence or absence of PAD. Median clinical follow-up was 5.9 (IQR: 5.1-6.8) years., Results: There were 461 patients with PAD (PCI: N = 307, CABG: N = 154), and 2919 patients without PAD (PCI: N = 1823, CABG: N = 1096). The cumulative 5-year mortality after coronary revascularization was 31.2 % in patients with PAD and 16.2 % in those without PAD (p < 0.0001). There was a higher risk of PCI relative to CABG for all-cause death in patients with and without PAD (adjusted HR, 1.59; 95%CI, 0.99-2.53; p = 0.054, and HR, 1.25; 95%CI, 1.01-1.56; p = 0.04) without interaction (p interaction p = 0.48); Nevertheless, there was no excess risk of PCI relative to CABG for cardiovascular death regardless of PAD., Conclusions: The long-term mortality after coronary revascularization was significantly higher in severe CAD patients with PAD than those without PAD. There was a higher mortality risk of PCI relative to CABG in patients with and without PAD without interaction, which was mainly driven by excess non-cardiovascular deaths., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is a scarcity of data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and diabetes. The Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention study multivessel cohort was a prospective, multicenter, single-arm trial enrolling 1,021 patients who underwent multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared the clinical outcomes between those patients with and without diabetes. The primary end point was a composite of death, myocardial infarction, stroke, or any coronary revascularization. There were 560 patients (54.8%) with diabetes and 461 patients (45.2%) without diabetes. The mean age was not different between the 2 groups (70.9 ± 9.7 vs 71.7 ± 10.4 years, p = 0.17). Patients with diabetes more often had chronic kidney disease and complex coronary artery disease, as indicated by the greater total number of stents and longer total stent length. The rate of meeting the OPTIVUS criteria was not different between the 2 groups (61.2% vs 60.7%, p = 0.83). The cumulative 1-year incidence of the primary end point was not different between the 2 groups (10.8% vs 9.8%, log-rank p = 0.65). After adjusting for confounders, the risk of diabetes relative to nondiabetes remained insignificant for the primary end point (hazard ratio 0.97, 95% confidence interval 0.65 to 1.44, p = 0.88). In conclusion, in patients who underwent multivessel IVUS-guided PCI and were managed with contemporary clinical practice, patients with diabetes had similar 1-year outcomes to patients without diabetes., Competing Interests: Declaration of competing interest Dr. Morimoto receives lecturer fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer (New York, New York), and Tsumura; receives manuscript fees from Bristol-Myers Squibb and Pfizer; is part of the advisory board for Novartis and Teijin. Dr. Matsuo receives lecturer fees from Abbott Medical, Boston Scientific, Philips, Zeon Medical, Kaneka, and Amgen. Dr. Kimura receives research grant from Abbott Medical, and Boston Scientific; receives honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; is on the advisory board of Abbott Medical, Boston Scientific, and Sanofi. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI)., Objectives: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI., Methods: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month., Results: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions., Conclusions: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111)., Competing Interests: Funding Support and Author Disclosures This study was funded by Abbott Medical Japan. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Watanabe has received personal fees from Abbott Medical Japan during the conduct of the study as well as personal fees from Daiichi-Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol Myers Squibb, and Otsuka outside the submitted work. Dr Morimoto has received lecturer fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Boards for Novartis and Teijin. Dr Suwa has received personal fees from Abbott Medical Japan and Daiichi-Sankyo outside the submitted work. Dr Kimura has received grants from Abbott Medical Japan and Boston Scientific; and has served on the Advisory Boards of Abbott Medical Japan and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Background: Recent clinical trials have shown that percutaneous coronary intervention (PCI) for non-culprit lesions (NCLs) reduces the risk of adverse events in patients with ST-segment elevation myocardial infarction (STEMI), but the effect on long-term outcomes remains unclear in acute coronary syndrome (ACS) patients and a real-world clinical setting., Methods: A retrospective observational cohort study of ACS patients who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital, Japan, was performed. The primary endpoint was the composite of cardiovascular disease death (CVD death) and non-fatal myocardial infarction (MI) during the mean follow-up period of 2.7 years, and a landmark analysis for the incidence of the primary endpoint from 31 days to 5 years between the multivessel PCI group and the culprit only PCI group was performed. Multivessel PCI was defined as PCI including non-infarct-related coronary arteries within 30 days after the onset of ACS., Results: Of the 1109 ACS patients with multivessel coronary artery disease of the current cohort, multivessel PCI was performed in 364 (33.2 %) patients. The incidence of the primary endpoint from 31 days to 5 years was significantly lower in the multivessel PCI group (4.0 % vs. 9.6 %, log-rank p = 0.0008). Multivariate Cox regression analysis showed that multivessel PCI was significantly associated with fewer cardiovascular events (HR 0.37, 95 % CI 0.19-0.67, p = 0.0008)., Conclusion: In ACS patients with multivessel coronary artery disease, multivessel PCI may reduce the risk of CVD death and non-fatal MI compared to culprit-lesion-only PCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several stent expansion criteria derived from the intravascular ultrasound (IVUS) evaluation have been proposed to predict future clinical outcomes, but optimal stent expansion criteria as a guide during percutaneous coronary intervention (PCI) are still controversial. There are no studies evaluating the utility of stent expansion criteria along with the clinical and procedural factors in predicting target lesion revascularization (TLR) after contemporary IVUS-guided PCI., Methods: OPTIVUS-Complex PCI study (Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention) multivessel cohort was a prospective multicenter study enrolling 961 patients undergoing multivessel PCI including left anterior descending coronary artery using IVUS with an intention to meet the prespecified criteria for optimal stent expansion. We compared several stent expansion criteria (minimum stent area [MSA], MSA/distal or average reference lumen area, MSA/distal or average reference vessel area, OPTIVUS criteria, IVUS-XPL [Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions] criteria, ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions] criteria, and modified MUSIC [Multicenter Ultrasound Stenting in Coronaries Study] criteria) as well as clinical, angiographic, and procedural characteristics between lesions with and without TLR., Results: Among 1957 lesions, the cumulative 1-year incidence of lesion-based TLR was 1.6% (30 lesions). Hemodialysis, treatment of proximal left anterior descending coronary artery lesions, calcified lesions, small proximal reference lumen area, and small MSA had univariate associations with TLR, while all of the stent expansion criteria except for MSA were not associated with TLR. The independent risk factors of TLR were calcified lesions (hazard ratio, 2.34 [95% CI, 1.03-5.32]; P =0.04) and small proximal reference lumen area (Tertile 1: hazard ratio, 7.01 [95% CI, 1.45-33.93]; P =0.02; and Tertile 2: hazard ratio, 5.40 [95% CI, 1.17-24.90]; P =0.03)., Conclusions: In contemporary IVUS-guided PCI practice, the 1-year incidence of TLR was very low. MSA, but not other stent expansion criteria, had univariate association with TLR. Independent risk factors of TLR were calcified lesions and small proximal reference lumen area, although the findings should be interpreted with caution due to small number of TLR events, limited lesion complexity, and short duration of follow-up., Competing Interests: Disclosures Dr Morimoto reports lecturer’s fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, and Tsumura; article fees from Bristol-Myers Squibb and Kowa; advisory board for Novartis and Teijin. Dr Tanabe reports honoraria from Abbott Medical, Boston Scientific, Japan Lifeline, Medtronic, Orbusneich, and Terumo. Dr Kimura reports research grant from Abbott Medical and Boston Scientific; honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; participation on advisory board from Abbott Medical, Boston Scientific, and Sanofi. The other authors report no conflicts.

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.

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.

Background: Aggressive lipid lowering by high-dose statin treatment has been established for the secondary prevention of coronary artery disease (CAD). Regarding the low-density lipoprotein cholesterol (LDL-C) level, however, the "The lower is the better" concept has been controversial to date. We hypothesized that there is an optimal LDL-C level, i.e., a "threshold" value, below which the incidence of cardiovascular events is no longer reduced. We undertook a subanalysis of the REAL-CAD study to explore whether such an optimal target LDL-C level exists by a novel analysis procedure to verify the existence of a monotonic relationship., Methods: For a total of 11,105 patients with CAD enrolled in the REAL-CAD study, the LDL-C level at 6 months after randomization and 5-year cardiovascular outcomes were assessed. We set the "threshold" value of the LDL-C level under which the hazards were assumed to be constant, by including an artificial covariate max (0, LDL-C - threshold) in the Cox model. The analysis was repeated with different LDL-C thresholds (every 10 mg/dl from 40 to 100 mg/dl) and the model fit was assessed by log-likelihood., Results: For primary outcomes such as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization, the model fit assessed by log-likelihood was best when a threshold LDL-C value of 70 mg/dl was assumed. And in the model with a threshold LDL-C ≥ 70 mg/dl, the hazard ratio was 1.07 (95% confidence interval 1.01-1.13) as the LDL-C increased by 10 mg/dl. Therefore, the risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dl, but when the level was further reduced, the risk was independent of LDL-C., Conclusions: Our analysis model suggests that a "threshold" value of LDL-C might exist for the secondary prevention of cardiovascular events in Japanese patients with CAD, and this threshold might be 70 mg/dl for primary composite outcomes., Trial Registration: http://www., Clinicaltrials: gov . Unique identifier: NCT01042730., (© 2022. The Author(s).)

The clinical significance of the CHADS 2 score remains unclear in patients with coronary artery disease (CAD) without atrial fibrillation (AF). Therefore, the purpose of this study was to evaluate the association between the CHADS 2 score and the long-term risk of ischemic stroke and its severity in patients with CAD with and without AF. Using the CREDO (Coronary Revascularization Demonstrating Outcome study)-Kyoto Registry Cohort-3, the present study population consisted of 11,516 patients with CAD who underwent percutaneous coronary intervention without oral anticoagulants at discharge. We divided the patients into 2 groups according to the presence (n = 721) or absence (n = 10,795) of AF. As the CHADS 2 score increased from 0 or 1 to 6, the cumulative 5-year incidence of ischemic stroke incrementally increased from 2.1% to 17.1% in patients without AF and from 4.2% to 40.7% in patients with AF. The cumulative 5-year incidence of ischemic stroke in patients without AF and a CHADS 2 score of 2 were numerically comparable to that in patients with AF and a CHADS 2 score of 1 (3.4% and 3.7%). In the 423 patients who developed ischemic stroke, the modified Rankin Scale score was not significantly different between patients with and without AF (p for trend = 0.12). In patients with and without AF, the increase in the CHADS 2 score was significantly associated with the greater prevalence of higher modified Rankin Scale scores (p for trend = 0.03 and <0.001, respectively). An increasing CHADS 2 score was associated with an incrementally increased risk for ischemic stroke and greater severity of ischemic stroke in patients with and without AF., Competing Interests: Disclosures Dr. Shiomi reports personal fees from Boston Scientific, Abbot Vascular, and Daiichi Sankyo. Dr. Morimoto reports modest honoraria from Bayer and Kowa and modest expert witness from Boston Scientific and Sanofi. Dr. Tamura reports personal fees from Daiichi Sankyo and Bayer. Dr. Furukawa reports personal fees from Daiichi Sankyo, Bayer, Bristol Myers Squibb, Pfizer, and Boehringer Ingelheim. Dr. Nakagawa reports a modest research grant from Abbott Vascular and Boston Scientific and modest honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr. Kimura reports significant honoraria from Abbott Vascular and modest honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease., Methods and Results: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001)., Conclusions: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD., Competing Interests: The authors have declared that no competing interests exist.

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.

Background: Optimal intensity is unclear for P2Y 12 receptor 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. P2Y 12 receptor 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 P2Y 12 receptor 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 P2Y 12 receptor blockers.

Recently, one observational study showed that patients with ST-segment elevation myocardial infarction (STEMI) without standard cardiovascular risk factors were associated with increased mortality compared with patients with risk factors. This unexpected result should be evaluated in other populations including those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and chronic coronary syndrome (CCS). Among 30,098 consecutive patients undergoing first coronary revascularization in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort-2 and 3, we compared clinical characteristics and outcomes between patients with and without risk factors stratified by their presentation (STEMI n = 8,312, NSTE-ACS n = 3,386, and CCS n = 18,400). Patients with risk factors were defined as having at least one of the following risk factors: hypertension, dyslipidemia, diabetes, and current smoking. The proportion of patients without risk factors was low (STEMI: 369 patients [4.4%], NSTE-ACS: 110 patients [3.2%], and CCS: 462 patients [2.5%]). Patients without risk factors compared with those with risk factors more often had advanced age, low body weight, and malignancy and less often had history of atherosclerotic disease and prescription of optimal medical therapy. In patients with STEMI, patients without risk factors compared with those with risk factors were more often women and more often had atrial fibrillation, long door-to-balloon time, and severe hemodynamic compromise. During a median of 5.6 years follow-up, patients without risk factors compared with those with risk factors had higher crude incidence of all-cause death. After adjusting confounders, the mortality risk was significant in patients with CCS (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01 to 1.49, p = 0.04) but not in patients with STEMI (HR 1.06, 95% CI 0.89 to 1.27, p = 0.52) and NSTE-ACS (HR 1.07, 95% CI, 0.74 to 1.54, p = 0.73). In conclusion, among patients undergoing coronary revascularization, patients without standard cardiovascular risk factors had higher crude incidence of all-cause death compared with those with at least one risk factor. After adjusting confounders, the mortality risk was significant in patients with CCS but not in patients with STEMI and NSTE-ACS., Competing Interests: Disclosures Dr. Morimoto receives lecturer's fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis, and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; and served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb, and Sanofi. Dr. Shiomi receives personal fees from Abbott Vascular, Boston Scientific, and Daiichi Sankyo. Dr. Kato receives honoraria from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Bristol-Meyers Squibb, Daiichi Sankyo, Merck Sharp & Dohme KK, Ono Pharmaceutical, Pfizer, Takeda, Tanabe-Mitsubishi; and research fund from Abbott Vascular, and Ono Pharmaceutical. Dr. Furukawa receives honoraria from Ono Pharmaceutical, Novartis, Daiichi Sankyo, Bayer, Otsuka Pharmaceutical, Kowa, Takeda, Sumitomo Dainippon Pharma, Pfizer, Bristol-Myers Squibb, and Sanofi. Dr. Nakagawa receives grant from Abbott Vascular and Boston Scientific, and personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, and Daiichi Sankyo. Dr. Kimura receives personal fees from Abbott Vascular, Abiomed, Astellas, Astellas Amgen BioPharma, AstraZeneca, Bayer, Boston Scientific, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Edwards Lifescience, Eisai, Daiichi Sankyo, Interscience, Japan Society for the Promotion of Science, Kowa, Kowa Pharmaceutical, Lifescience, Medical Review, Merck Sharp & Dohme, MSD Life Science Foundation, Mitsubishi Tanabe Pharma, Novartis Pharma, Ono Pharmaceutical, OrbusNeich, Otsuka Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Philips, Public Health Research Foundation, Sanofi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Terumo, Toray, and Tsumura. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) is a standard treatment in patients with stable coronary artery disease (CAD); however, periprocedural myocardial infarction (PMI) remains a common complication of PCI. Aggressive lipid-lowering therapy with statin has shown to reduce the incidence of PMI by preventing coronary microvascular dysfunction. It is unclear whether evolocumab, a potent lipid-lowering agent, could diminish microvascular damage after PCI. The EVOCATION trial (jRCTs051180022) is a multicenter, randomized, open-label, active-controlled, parallel-group, exploratory, investigator-initiated clinical study to evaluate whether pretreatment with evolocumab could decrease the index of microvascular resistance (IMR) after PCI in patients with stable CAD. This study population consists of 100 patients with stable CAD who will undergo PCI and have high low-density lipoprotein cholesterol levels despite administration of maximum tolerated dose of statins for at least 2 weeks. Eligible patients are randomized in a 1:1 ratio to receive either evolocumab 140 mg every 2 weeks in addition to standard of care treatment or standard of care treatment only for 2-6 weeks before PCI. The primary endpoint is IMR after PCI. The EVOCATION trial will evaluate whether pretreatment with evolocumab reduces periprocedural microvascular damage in patients with stable CAD undergoing PCI., (Copyright © 2021. Published by Elsevier Ltd.)

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.

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, p trend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, p trend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long-term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, we identified the current study population of 3380 patients with three-vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow-up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P =0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28-2.42; P <0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80-1.34; P =0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) might be an important determinant in choosing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). However, there is a scarcity of studies evaluating the effect of CKD on long-term outcomes after PCI relative to CABG in the population including severe CKD. Among 30257 consecutive patients patients who underwent first coronary revascularization with PCI or isolated CABG in the CREDO-Kyoto PCI/CABG registry Cohort-2 (n = 15330) and Cohort-3 (n = 14,927), we identified the current study population of 12,878 patients with multivessel or left main disease, and compared long-term clinical outcomes between PCI and CABG stratified by the subgroups based on the stages of CKD (no CKD: eGFR >=60 ml/min/1.73m 2 , moderate CKD: 60> eGFR >=30 ml/min/1.73m 2 , and severe CKD: eGFR <30 ml/min/1.73m 2 or dialysis). There were 6,999 patients without CKD (PCI: n = 5,268, and CABG: n = 1,731), 4,427 patients with moderate CKD (PCI: n = 3,226, and CABG: n = 1,201), and 1,452 patients with severe CKD (PCI: n = 989, and CABG: n = 463). During median 5.6 years of follow-up, the excess mortality risk of PCI relative to CABG was significant regardless of the stages of CKD without interaction (no CKD: HR, 1.36; 95%CI, 1.12 to 1.65; p = 0.002, moderate CKD: HR, 1.40; 95%CI, 1.17 to 1.67; p <0.001, and severe CKD: HR, 1.33; 95%CI, 1.09 to 1.62; p = 0.004, Interaction p = 0.83). There were no significant interactions between CKD and the effect of PCI relative to CABG for all the outcome measures evaluated. In conclusion, PCI compared with CABG was associated with significantly higher risk for all-cause death regardless of the stages of CKD without any significant interaction., Competing Interests: Disclosures Dr. Morimoto reports honoraria from Bayer and Kowa, and expert witness from Boston Scientific and Sanofi. Dr. Shiomi reports honoraria from Abbott Vascular, and Boston Scientific. Dr. Furukawa reports honoraria from Bayer, Kowa, and Sanofi. Dr. Nakagawa reports research grant from Abbott Vascular and Boston Scientific, and honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr. Kimura reports honoraria from Abbott Vascular, Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Long-term safety of percutaneous coronary intervention (PCI) as compared with coronary artery bypass grafting (CABG) is still controversial in patients with unprotected left main coronary artery disease (ULMCAD), and there is a scarcity of real-world data on the comparative long-term clinical outcomes between PCI and CABG for ULMCAD in new-generation drug-eluting stents era. The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013, and we identified 855 patients with ULMCAD (PCI: N = 383 [45%], and CABG: N = 472 [55%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.5 (interquartile range: 3.9 to 6.6) years. The cumulative 5-year incidence of all-cause death was not significantly different between the PCI and CABG groups (21.9% vs 17.6%, Log-rank p = 0.13). After adjusting confounders, the excess risk of PCI relative to CABG remained insignificant for all-cause death (HR, 1.00; 95% CI, 0.68 to 1.47; p = 0.99). There were significant excess risks of PCI relative to CABG for myocardial infarction and any coronary revascularization (HR, 2.07; 95% CI, 1.30 to 3.37; p = 0.002, and HR, 2.96; 95% CI, 1.96 to 4.46; p < 0.001), whereas there was no significant excess risk of PCI relative to CABG for stroke (HR, 0.85; 95% CI, 0.50 to 1.41; p = 0.52). In conclusion, there was no excess long-term mortality risk of PCI relative to CABG, while the excess risks of PCI relative to CABG were significant for myocardial infarction and any coronary revascularization in the present study population reflecting real-world clinical practice in Japan., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To evaluate patient characteristics and long-term outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) in the past two decades., Design: Multicenter retrospective study., Setting: The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) Registry Cohort-2 (2005-2007) and Cohort-3 (2011-2013)., Participants: 3254 patients with NSTEACS who underwent first coronary revascularisation., Primary and Secondary Outcome Measures: The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, any coronary revascularisation and target vessel revascularisation., Results: Patients in Cohort-3 were older and more often had heart failure at admission than those in Cohort-2. The prevalence of PCI, emergency procedure and guideline-directed medical therapy was higher in Cohort-3 than in Cohort-2. In patients who received PCI, the prevalence of transradial approach, drug-eluting stent use and intravascular ultrasound use was higher in Cohort-3 than in Cohort-2. There was no change in 3-year adjusted mortality risk from Cohort-2 to Cohort-3 (HR 1.00, 95% CI 0.83 to 1.22, p=0.97). Patients in Cohort-3 compared with those in Cohort-2 were associated with lower adjusted risks for stroke (HR 0.65, 95% CI 0.46 to 0.92, p=0.02) and any coronary revascularisation (HR 0.76, 95%CI 0.66 to 0.87, p<0.001), but with higher risk for major bleeding (HR 1.25, 95% CI 1.06 to 1.47, p=0.008). The unadjusted risk for definite stent thrombosis was lower in Cohort-3 than in Cohort 2 (HR 0.29, 95% CI 0.11 to 0.67, p=0.003)., Conclusions: In the past two decades, we did not find improvement for mortality in patients with NSTEACS. We observed a reduction in the risks for definite stent thrombosis, stroke and any coronary revascularisation, but an increase in the risk for major bleeding., Competing Interests: Competing interests: HS reports personal fees from Abbott Vascular, Boston Scientific and Daiichi Sankyo. TM reports lecturer’s fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb and Sanofi. NE reports personal fees from Abbott Vascular, Medtronic, Terumo, Bayer, Boston Scientific, Daiichi-Sankyo, Edwards Lifescience, Pfizer, Bristol Myers Squibb, Takeda and Boehringer Ingelheim. YF reports personal fees from Daiichi Sankyo, Bayer, Sanofi, Kowa, Pfizer, Bristol-Myers Squibb, Otsuka Parmaceutical, Sumitomo Dainippon Pharma, Takeda and Ono Pharmaceutical. YN reports grant from Abbott Vascular and Boston Scientific, and reports personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo. TK reports personal fees from Abbott Vascular, MSD, Eisai, Edwards Lifescience, Ono Pharmaceutical, Tsumura, Medical Review, Kowa, Sanofi, Daiichi Sankyo, Takeda Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Abiomed, Bayer, Bristol-Myers Squibb, Boston Scientific, Lifescience, Toray, Astellas Amgen Biopharma, Astellas, AstraZeneca, Otsuka Parmaceutical, OrbusNeich, MSD Life Science Foundation, Public Health Research Foundation, Chugai Pharmaceutical, Boehringer Ingelheim, Japan Society for the Promotion of Science, Interscience, Philips, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Terumo, Novartis Pharma and Sumitomo Dainippon Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32-1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42-1.45; P for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40-1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43-1.84; P for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14-1.58; P for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent-2 [STOPDAPT-2]; NCT02619760.

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.

Although an elevated neutrophil to lymphocyte ratio (NLR) has been associated with the adverse outcomes of coronary artery disease (CAD), less is known about its prognostic value among patients with low high-sensitivity C-reactive protein (hs-CRP) levels. We enrolled 2,591 consecutive patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) and had available data on preprocedural hs-CRP and NLR between 2000 and 2016. Of these patients, 1,951 with low-grade hs-CRP levels (< 2.0 mg/L) were divided into quartiles based on the NLR values. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke after the index PCI. Clinical follow-up data were obtained up to 5 years. The median NLR was 1.9 (interquartile range: 1.5-2.5). During the follow-up, 102 events occurred (5.2%), with a cumulative incidence that was significantly higher in the highest NLR group than in the other groups (log-rank, P = 0.02). After adjusting for the other cardiovascular risk factors, the risk for the primary endpoint was significantly higher for the highest than in the lowest NLR group (HR 1.97, 95% CI 1.09-3.54, P = 0.02). Increasing NLR as a continuous variable was associated with the incidence of adverse cardiovascular events (HR 1.85 per log 1 NLR increase, 95% CI 1.19-2.88, P = 0.007). In conclusion, the adverse long-term clinical outcomes of CAD patients with low-grade hs-CRP levels has been independently predicted by increased NLR level. NLR could be useful for risk stratification of CAD patients with increased inflammatory marker levels.

Cardiovascular events still occur despite statin-based lipid-lowering therapy in patients with coronary artery disease (CAD). LR11, a member of the low-density lipoprotein receptor family, is a novel marker for the proliferation of intimal smooth muscle cells, which are critical to atherosclerotic plaque formation. We evaluated the impact of LR11 on long-term clinical outcomes in CAD patients treated with statins after percutaneous coronary intervention (PCI).This study included 223 consecutive CAD patients (age, 64.5 ± 9.6 years; male, 81.2%) treated with statin after first PCI between March 2003 and December 2004 at our institution. Patients were stratified to two groups according to LR11 levels (median). Composite cardiovascular disease (CVD) endpoints that included cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke were compared between groups.The rate of CVD endpoints was significantly higher in the high LR11 group (log-rank, P = 0.0029) during the median follow-up period of 2844 days. Multivariate Cox regression analysis showed that a higher LR11 level was significantly associated with adverse clinical outcomes (adjusted hazard ratio for composite CVD endpoints, 2.47; 95% confidence interval, 1.29-4.92; P = 0.006).Elevated levels of LR11 were significantly associated with long-term clinical outcomes among CAD patients treated with statins after first PCI.

Although high-sensitivity C-reactive protein (hs-CRP) has been used to predict the risk of adverse cardiac events in patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs), little is known about the association between hs-CRP and long-term outcomes in patients with preserved renal function.Here, we studied 1,153 patients with stable CAD and preserved renal function (estimated glomerular filtration rate: > 60 mL/minute/1.73 m 2 ) who underwent their first PCI between 2000 and 2011. Those with available data on preprocedural hs-CRP were included. Patients were assigned to tertiles according to preprocedural hs-CRP levels. The incidence of major adverse cardiac events (MACE), including all-cause death and nonfatal myocardial infarction, was evaluated. During a median follow-up period of 7.5 years, Kaplan-Meier curves showed ongoing divergence in the rates of MACE among the hs-CRP tertiles (hs-CRP < 0.05 mg/L, 12.1%; 0.05-0.17 mg/L, 12.1%; > 0.17 mg/L, 21.6%; log-rank P = 0.003). After adjusting for the established cardiovascular risk factors, hs-CRP levels were found to be associated with a higher incidence of MACE (hazard ratio [HR]: 3.65, 95% confidence interval [CI]: 1.77-7.07; P = 0.0008) and a higher rate of all-cause mortality (HR: 5.14, 95% CI: 2.38-10.30; P < 0.0001).In conclusion, this long-term registry showed that preprocedural hs-CRP measurement is clinically useful for long-term risk assessments in patients with stable CAD and preserved renal function.

Background: The use of serial intravascular ultrasound (IVUS) for coronary atherosclerosis has offered valuable insight into plaque regression (PR) or progression. However, the beneficial effects of PR on the long-term clinical outcomes in patients with acute coronary syndrome (ACS) remain unclear. We aimed to evaluate the impact of coronary plaque change in patients following primary percutaneous coronary intervention., Methods: We retrospectively analyzed data from 4 prospective clinical trials involving 173 patients with ACS who underwent serial IVUS of non-culprit lesions on statin treatment at baseline and at 6 or 8 months of follow-up. The relationship of the IVUS findings with the change in percent atheroma volume (PAV), on-treatment low-density lipoprotein cholesterol (LDL-C), and major adverse cardiac and cerebrovascular events (MACCE) were investigated., Results: In our serial IVUS analysis, baseline plaque volume and PAV were 79.6mm 3 and 46.0%, respectively. The overall change in PAV was -1.5% [interquartile range (IQR): -4.1% to 1.0%], and PR (i.e. PAV change from baseline <0) was observed in 67.1% of patients. They were followed up observationally for a mean of 3.5 years and a total of 37 MACCE occurred. The rate of MACCE tended to be lower in patients with PR than in those without PR (18.1% vs. 28.7%, p=0.14). A multivariate Cox hazard model analysis demonstrated that achievement of both PR and on-treatment low LDL-C levels (<70mg/dL) was the only significant independent predictor of MACCE (hazard ratio: 0.42, 95% confidence interval: 0.19-0.88; p=0.02)., Conclusions: Achievement of both PR and sufficient lowering of the LDL-C was clinically important in post-ACS management., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: A low 1,5-anhydro-D-glucitol (AG) blood level is considered a clinical marker of postprandial hyperglycemia. Previous studies reported that 1,5-AG levels were associated with vascular endothelial dysfunction and coronary artery disease (CAD). However, the association between 1,5-AG levels and coronary artery plaque in patients with CAD is unclear., Methods: This study included 161 patients who underwent percutaneous coronary intervention for CAD. The culprit plaque characteristics and the extent of coronary calcification, which was measured by the angle of its arc, were assessed by preintervention intravascular ultrasound (IVUS). Patients with chronic kidney disease or glycosylated hemoglobin ≥ 7.0 were excluded. Patients were divided into 2 groups according to serum 1,5-AG levels (< 14.0 μg/mL vs. ≥ 14 μg/mL)., Results: The total atheroma volume and the presence of IVUS-attenuated plaque in the culprit lesions were similar between groups. Calcified plaques were frequently observed in the low 1,5-AG group (p = 0.06). Compared with the high 1,5-AG group, the low 1,5-AG group had significantly higher median maximum calcification (144° vs. 107°, p = 0.03) and more frequent calcified plaques with a maximum calcification angle of ≥ 180° (34.0% vs. 13.2%, p = 0.003). Multivariate logistic regression analysis showed that a low 1,5-AG level was a significant predictor of a greater calcification angle (> 180°) (OR 2.64, 95% CI 1.10-6.29, p = 0.03)., Conclusions: Low 1,5-AG level, which indicated postprandial hyperglycemia, was associated with the severity of coronary artery calcification. Further studies are needed to clarify the effects of postprandial hyperglycemia on coronary artery calcification.

Objectives: The aim of this study was to compare 7-year outcomes between the first-generation sirolimus-eluting stent (SES) and the new-generation everolimus-eluting stent (EES) in a randomized clinical trial., Background: There is a scarcity of very long-term (beyond 5 years) data from clinical trials investigating whether new-generation drug-eluting stents have clear clinical advantages over first-generation drug-eluting stents., Methods: RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) is the largest randomized trial comparing EES with SES (NCT01035450). Among a total of 3,197 patients in the original RESET population from 100 centers, the present extended 7-year follow-up study was conducted in 2,667 patients from 75 centers after excluding those patients enrolled from centers that denied participation. Complete 7-year follow-up was achieved in 91.5% of patients., Results: The cumulative 7-year incidence of the primary efficacy endpoint of target lesion revascularization was not significantly different between EES and SES (10.2% vs. 11.7%; hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.10; p = 0.24). The risk for the primary safety endpoint of death or myocardial infarction trended lower with EES than with SES (20.6% vs. 23.6%; hazard ratio: 0.85; 95% confidence interval: 0.72 to 1.005; p = 0.06). The cumulative 7-year incidence of definite stent thrombosis was very low and similar between EES and SES (0.9% vs. 1.0%; p = 0.82). The lower risk of EES relative to SES was significant for the composite secondary endpoint of target lesion failure (13.3% vs. 18.1%; hazard ratio: 0.72; 95% confidence interval: 0.59 to 0.88; p = 0.001)., Conclusions: During 7 years of follow-up, the risk for target lesion revascularization was not significantly different between the new-generation EES and the first-generation SES., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting., Methods: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months., Results: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS 2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively., Conclusions: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.

Introduction: C-reactive protein (CRP) is an established marker for vascular inflammation and predictor of adverse cardiovascular events, but the prognostic value of preprocedural CRP in coronary artery disease (CAD) patients who have undergone percutaneous coronary intervention (PCI) remains controversial. Furthermore, the impact of CRP levels during follow-up in CAD patients after PCI on long-term adverse clinical outcomes is uncertain. We evaluated the association between high-sensitivity (hs)-CRP values at follow-up angiography and long-term clinical outcomes in CAD patients after coronary intervention., Methods: We prospectively enrolled 3507 consecutive CAD patients who underwent first PCI between 1997 and 2011 at our institution. We identified 2509 patients (71.5%) who underwent follow-up angiography (6-8 months after PCI). Of those, 1605 patients (45.8%) who had data available for hs-CRP at follow-up angiography were stratified into three groups according to tertiles of hs-CRP level at the time of follow-up angiography. The primary endpoint was composite of all-cause death and non-fatal acute coronary syndrome (ACS)., Results: Median follow-up was 1716 days. The cumulative incidence of all-cause death and ACS differed significantly among groups (log-rank, p=0.0002). Multivariate Cox regression analysis showed that a higher hs-CRP level at follow-up angiography was associated with a greater risk of all-cause death and ACS [adjusted hazard ratio (HR) for all-cause death and ACS 2.14, 95% confidence interval (CI) 1.43-3.27, p=0.0002., Conclusion: Elevated hs-CRP levels during follow-up were significantly associated with higher frequencies of adverse long-term clinical outcomes in patients with CAD after PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Previous studies have reported the prognostic value of objective nutritional indices such as the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI). However, the effects of these indices in patients with coronary artery disease (CAD) who have undergone percutaneous coronary intervention (PCI) remain unclear. Furthermore, there are insufficient data to combine these indices. A total of 1984 patients who underwent elective PCI were enrolled. The Combined Objective Nutritional Score was determined by assigning 1 point each for high CONUT score (3-12), low GNRI (< 98) or low PNI (< 45). Patients were grouped into normal nutritional status (0 points), mild-to-moderate malnutrition (1-2 points) and severe malnutrition (3 points). Incidences of all-cause death and cardiac death were evaluated. Among the 1984 patients, 514 (25.9%) and 244 (12.3%) had mild-to-moderate and severe malnutrition, respectively. During follow-up (median 7.4 years), 293 all-cause deaths were identified, including 92 cardiac deaths. Kaplan-Meier curves showed ongoing divergence in rates of death among nutritional statuses determined by the novel score (log rank test, p < 0.0001). Multivariate Cox hazard analysis showed that patients with a Combined Objective Nutritional Score of 3 showed 2.91-fold (95% confidence interval (CI) 2.10-4.00; p < 0.0001) and 2.16-fold (95% CI 1.15-3.92; p = 0.02) increases in risk of mortality and cardiac mortality compared with patients with a Combined Objective Nutritional Score of 0. In conclusion, malnutrition as evaluated by the Combined Objective Nutritional Score was significantly associated with worse long-term cardiovascular outcomes among CAD patients who underwent PCI.

Background and Aims: Although an elevated mean platelet volume (MPV) has been associated with poor clinical outcomes after acute coronary syndrome (ACS), the association between MPV and long-term outcomes in patients with stable coronary artery disease (CAD) remains uncertain. We aimed to investigate the impact of pre-procedural MPV levels in patients following elective percutaneous coronary intervention (PCI)., Methods: We studied 2872 stable CAD patients who underwent their first PCI and who had available data on pre-procedural MPV between 2002 and 2016. Patients were divided into quartiles based on their MPV. The incidences of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, were evaluated., Results: The median MPV was 10.4 fL (interquartile range: 9.8-11.0). During a median follow-up of 5.6 years, 498 (17.3%) MACE were identified, with a cumulative incidence significantly higher in the lowest MPV group than in other groups (p < 0.01). After adjustment for platelet count and the other cardiovascular risk factors, the lowest MPV group had a significantly higher risk of MACE compared with the highest MPV groups (hazard ratio: 1.43, 95% confidence interval 1.10-1.86, p = 0.009). Decreasing MPV as a continuous variable was associated with the incidence of MACE (hazard ratio: 1.16 per 1 fL decrease, 95% confidence interval 1.04-1.30, p = 0.007)., Conclusions: Contrary to previous studies on ACS patients, this study showed that a low MPV was associated with worse clinical outcomes among stable CAD patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Malnutrition has recently been reported to correlate with prognosis in patients with heart failure. However, the prognostic significance of nutritional status in patients with stable coronary artery disease (CAD) is unknown. The present study sought to examine the association between nutritional status assessed by the prognostic nutritional index (PNI) and cardiovascular outcomes in patients with stable CAD., Methods: A total of 1988 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011 were examined. The PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm 3 ). Patients were assigned to tertiles based on their PNI. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated., Results: The median PNI was 48.9 (interquartile range: 45.5-52.1). During the median follow-up of 7.5 years, Kaplan-Meier analysis showed that patients with lower PNI tertiles had higher rates of MACE (PNI <46.7: 35.5%; 46.7-50.8: 22.3%; >50.8: 16.0%; log-rank p<0.0001). After adjusting for other risk factors, the PNI was independently associated with MACE (hazard ratio 2.05 per 10 PNI decrease, 95% confidence interval: 1.66-2.54, p<0.0001). Adding the PNI to a baseline model with established risk factors improved the C-index (p=0.03), net reclassification improvement (p=0.03), and integrated discrimination improvement (p=0.0001)., Conclusions: The PNI was significantly associated with long-term cardiovascular outcomes in patients with stable CAD. Assessing PNI may be useful for risk stratification of CAD patients undergoing elective PCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Previous intravascular ultrasound studies suggested the association of stent underexpansion with increased risk of stent thrombosis and restenosis. However, no previous study has addressed the association of the suboptimal angiographic result with target-lesion revascularization (TLR) in patients receiving new-generation drug-eluting stents (DES)., Methods and Results: RESET (Randomized evaluation of sirolimus-eluting versus everolimus-eluting stent trial) and NEXT (NOBORI biolimus-eluting versus XIENCE/PROMUS everolimus-eluting stent trial) are prospective, multicenter, randomized "DES versus DES" trials; 3196 patients and 3235 patients were enrolled in the RESET and NEXT, respectively. Using the pooled individual patient-level data, the current study population consisted of 3679 patients who received single-lesion treatment using new-generation DES such as everolimus-eluting stent and biolimus-eluting stent. The study population was divided into 3 groups according to the residual in-stent % diameter stenosis (%DS) after stent implantation by offline quantitative coronary angiography assessed in a core angiographic laboratory (optimal group: %DS <10%, intermediate group: %DS=10% to 20%, suboptimal group: %DS ≧20%). The cumulative 3-year incidence of TLR was significantly higher in the suboptimal group than in the intermediate and optimal groups (9.8% versus 5.8% versus 5.7%, log-rank P =0.004). Even after adjusting for the clinical, angiographic, and procedural characteristics, the excess TLR risk of the suboptimal group relative to the optimal group remained significant (hazard ratio: 1.65, 95% confidence interval, 1.14-2.41, P =0.009). The excess TLR risk of the suboptimal group relative to the optimal group was consistently seen across all the subgroups including heavy calcification., Conclusions: The residual angiographic in-stent %DS ≥20% was associated with increased risk for TLR in patients treated with the new-generation DES., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The comparative efficacy of second-generation (G2) vs. first-generation (G1) drug-eluting stents (DES) for calcified coronary lesions is unknown.Methods and Results:We compared the 3-year clinical outcomes of patients with G1- or G2-DES according to the presence or absence of calcified coronary lesions as assessed in an angiographic core laboratory using data from 2 large-scale prospective multicenter randomized trials, RESET and NEXT. G1-DES and G2-DES were implanted in 299 and 1,033 patients, respectively, in the Calc stratum (≥1 lesion with moderate/severe calcification), and 1,208 and 3,550 patients, respectively, in the Non-calc stratum (no/mild calcification). The patients in the Calc stratum had a significantly higher adjusted risk for the primary outcome measure (any target-lesion revascularization (TLR)) than those in the Non-calc stratum (HR: 1.38, 95% CI: 1.11-1.71, P=0.004). The cumulative 3-year incidence of any TLR was not significantly different between the G1-DES and G2-DES groups in both the Calc and Non-calc strata (12.1% vs. 9.7%, P=0.22, and 6.8% vs. 6.1%, P=0.44, respectively). After adjusting for confounders, the effect of G2DES relative to G1-DES for any TLR remained insignificant in both the Calc and Non-calc strata (HR: 0.78, 95% CI: 0.48-1.25, P=0.3, and HR: 0.84, 95% CI: 0.61-1.17, P=0.31, respectively, P interaction=0.55)., Conclusions: The effect of G2-DES relative to G1-DES for TLR was not significantly different regardless of the presence or absence of lesion calcification.

Background: Recently, malnutrition has been shown to be related to worse clinical outcomes in patients with heart failure. However, the association between nutritional status and clinical outcomes in patients with coronary artery disease (CAD) remains unclear. We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT; range 0-12, higher = worse, consisting of serum albumin, cholesterol and lymphocytes) score in patients with CAD., Methods: The CONUT score was measured on admission in a total of 1987 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011. Patients were divided into two groups according to their CONUT score (0-1 vs. ≥2). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated., Results: The median CONUT score was 1 (interquartile range 0-2). During the median follow-up of 7.4 years, 342 MACE occurred (17.2%). Kaplan-Meier curves revealed that patients with high CONUT scores had higher rates of MACE (log-rank p < 0.0001). High CONUT scores showed a significant increase in the incidence of MACE compared with low CONUT scores, even after adjusting for confounding factors (hazard ratio: 1.64, 95% confidence interval 1.30-2.07, p < 0.0001). Adding CONUT scores to a baseline model with established risk factors improved the C-index (p = 0.02), net reclassification improvement (p = 0.004) and integrated discrimination improvement (p = 0.0003)., Conclusions: Nutritional status assessed by the CONUT score was significantly associated with long-term clinical outcomes in patients with CAD. Pre-PCI assessment of the CONUT score may provide useful prognostic information.

Aims: Cardiovascular risk persists despite intensive lipid lowering therapy using statins. Serum levels of lipoprotein (a) [Lp(a)] can be a residual cardiovascular risk for adverse events. Aim of the present study was to evaluate the impact of Lp(a) on long-term clinical outcomes in patients treated with statin after percutaneous coronary intervention., Methods: We prospectively enrolled 3507 consecutive CAD patients who underwent a first percutaneous coronary intervention (PCI) between 1997 and 2011 at our institution. We identified 1768 patients (50.4%) who had treated with statin during PCI. Eligible 1336 patients were stratified to two groups according to Lp(a) levels (median Lp (a) 21.5 mg/dL). The primary outcome was major adverse cardiac events (MACE) including cardiac death and non-fatal acute coronary syndrome., Results: MACE occurred 144 (10.8%) including 34 (2.5%) cardiac death and 110 (8.7%) non-fatal ACS during median follow-up period of 1920 days. The cumulative rate of MACE was significantly higher in group with high Lp(a) group (log-rank p=0.0460). Multivariate Cox regression analysis showed a significant correlation between Lp (a) levels treated as a natural logarithm-transformed continuous variable and increased MACE (adjusted HR for MACE 1.28, 95%CI 1.04-1.58, p=0.0184)Conclusion: Elevated levels of Lp(a) is significantly associated with long-term adverse clinical outcomes among CAD patients who received statin therapy after PCI.

Background and Aims: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse clinical outcomes in patients with acute coronary syndrome. However, the long-term prognostic value of NLR in stable coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not been fully investigated. The aim of this study was to determine whether NLR is an independent predictor of long-term cardiac outcomes after PCI., Methods: A total of 2070 patients with CAD who underwent elective PCI were enrolled in the study. Patients were divided into three groups by NLR tertile (<1.7, 1.7-2.5, and 2.5<). Incidences of all-cause death and cardiac death were evaluated., Results: During follow-up (median, 7.4 years), 300 patients (14.5%) died. Kaplan-Meier curves revealed ongoing divergence in rates of all-cause death and cardiac death among tertiles (both log-rank p < 0.01). In multivariate analysis, using the lowest tertile as reference, the highest tertile remained significantly associated with greater incidences of all-cause death (hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.29-2.34; p = 0.0002). Continuous NLR values were also an independent predictor of all-cause death (HR, 1.87 per log NLR 1 increase; 95% CI, 1.50-2.32; p < 0.0001) and cardiac death (HR, 2.11; 95% CI, 1.46-3.05; p < 0.0001). Adding NLR values to a baseline model with established risk factors improved the C-index (p = 0.002), net reclassification improvement (p = 0.008) and integrated discrimination improvement (p = 0.0001) for all-cause death., Conclusions: Elevated NLR was an independent predictor of long-term cardiovascular outcomes after elective PCI. Assessing pre-PCI NLR may be useful for risk stratification of stable CAD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Epidemiological studies have demonstrated an association between low serum albumin levels and both coronary artery disease (CAD) and mortality. However, the long-term clinical impact of low serum albumin level in patients with CAD undergoing percutaneous coronary intervention (PCI) has not yet been fully investigated. We studied 2860 all-comer patients with CAD who underwent their first PCI and had data available for pre-procedural serum albumin between 2000 and 2011. Patients were assigned to tertiles based on pre-procedural albumin levels. We evaluated the incidence of major adverse cardiac events (MACE), including all-cause death and nonfatal myocardial infarction. Mean albumin level was 4.0 ± 0.5 g/dL. Lower albumin levels were associated with older age, lower body mass index (BMI), and higher prevalences of female sex, ACS and chronic kidney disease (CKD). During the median follow-up period of 7.4 years, Kaplan-Meier curves showed ongoing divergence in rates of MACE among albumin tertiles (albumin <3.8 g/dl: 44.3% vs. 3.8-4.1 g/dl: 38.0% vs. >4.1 g/dl: 22.9%; log-rank p < 0.0001). After adjusting for established cardiovascular risk factors including age, acute coronary syndrome, BMI and CKD, serum albumin levels were significantly associated with incidence of MACE (HR 1.74 per 1-g/dl decrease, 95% CI 1.34-2.26, p < 0.0001) and all-cause mortality (HR 1.74, 95% CI 1.30-2.33, p = 0.0002). Pre-PCI low serum albumin level was associated with worse long-term outcomes, independent of traditional risk factors. Assessing albumin levels may allow risk stratification in patients with CAD undergoing PCI.

Background: Both inflammation and malnutrition have been reported to be closely linked to atherosclerosis, especially in patients with chronic kidney disease (CKD). The combined effects of serum albumin and C-reactive protein (CRP) on clinical outcomes after percutaneous coronary intervention (PCI) were investigated.Methods and Results:A total of 2,164 all-comer patients with coronary artery disease who underwent their first PCI and had data available for preprocedural serum albumin and hs-CRP levels between 2000 and 2011 were studied. Patients were assigned to 4 groups according to their median serum albumin and CRP levels (4.1 g/dL and 0.10 mg/dL, respectively). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction (MI), was evaluated. During a median follow-up period of 7.5 years, 331 cases of MACE (15.3%), including 270 deaths and 61 non-fatal MIs, occurred. Kaplan-Meier curves showed that the rates of MACE differed significantly among the groups (log-rank P<0.0001), even stratified by with or without CKD (both log-rank P<0.0001). After adjustment for established cardiovascular risk factors, low serum albumin with high CRP levels was associated with adverse cardiac events (hazard ratio 2.55, 95% confidence interval 1.72-3,88, P<0.0001, high albumin/low CRP group as reference)., Conclusions: The presence of both low serum albumin and high CRP levels conferred a synergistic adverse effect on the risk for long-term MACE in patients undergoing PCI.

Malnutrition has been identified as an important predictor of poor clinical outcomes in patients with heart failure. The aim of this study is to examine the prognostic impact of nutritional status in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). The impact of nutrition, assessed using the geriatric nutritional risk index (GNRI) calculated by serum albumin and body mass index, was evaluated in 2,853 patients with CAD who underwent their first PCI between 2000 and 2011. Patients were assigned to tertiles based on their GNRI levels. The incidences of all-cause death and cardiac death were assessed. The median GNRI values were 101 (interquartile range 95 to 106). Lower GNRI levels were associated with older age and higher prevalence of acute coronary syndrome and chronic kidney disease. During the median follow-up period of 7.4 years, Kaplan-Meier curves showed ongoing divergence in rates of mortality among tertiles (GNRI <98: 35.1%; 98 to 104: 20.6%; ≥104: 12.1%; log-rank p <0.0001). Stratification analysis by age also showed that the lowest GNRI tertile was associated with mortality in both patients <65 years and those ≥65 years. After adjusting for established cardiovascular risk factors, lower GNRI was an independent predictor of all-cause death (hazard ratio 1.55 per 10 decrease, 95% confidence interval 1.30 to 1.84, p <0.0001) and cardiac death (hazard ratio 1.44, 95% confidence interval 1.08 to 1.90, p = 0.01). In conclusion, nutritional status was associated with long-term clinical outcomes in CAD patients after PCI. Evaluation of GNRI carries important prognostic information and may guide the therapeutic approach to such patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The incidence of adverse outcomes after percutaneous coronary intervention (PCI) is higher in women than in men. Statins reduce the likelihood of cardiovascular events arising in patients with coronary artery disease (CAD), but the impact of gender difference on long-term outcomes of PCI for CAD under statin treatment has not been established. We prospectively enrolled 3,580 consecutive patients with CAD who were treated by PCI at our institution between 2000 and 2011. Among these, 2,009 (43.9 %; male, n = 1619; female, n = 390) were under statin therapy at the time of PCI. We evaluated the incidence of major adverse cardiac events (MACE) including all-cause death and acute coronary syndrome (ACS). Age was significantly more advanced and the prevalences of hypertension and chronic kidney disease were higher among the female, than the male patients. Low-density lipoprotein cholesterol levels were significantly higher in women than in men (111.5 ± 38.9 vs. 107.5 ± 3 3.9 mg/dL, p = 0.04). During a median follow-up period of 6.3 years, MACE that occurred in 336 (16.7 %) patients included 206 (10.2 %) with all-cause death and 154 (7.7 %) with ACS. The cumulative rate of MACE tended to be higher in women than in men but the difference did not reach significance (19.7 vs. 16.0 %; p = 0.08, log-rank test). Multivariable Cox regression analysis showed that being female was not associated with MACE after adjusting for age (HR 1.22; 95 % CI 0.94-1.57; p = 0.13) and other variables (HR 1.14; 95 % CI 0.86-1.49; p = 0.35). Long-term clinical outcomes were comparable between male and female patients with coronary artery disease who were administered with statins and underwent PCI even though the baseline characteristics were worse among the females.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherosclerotic and cardioprotective effects in vitro. However, the impact of DPP-4 inhibitors on coronary plaque remains unclear. We sought to assess the effect of sitagliptin on coronary plaque volume (PV) and stabilization in diabetic patients with acute coronary syndrome (ACS)., Methods: The ESPECIAL-ACS was a prospective, randomized, open-label, parallel group study at 4 Japanese centers to assess the effect of 6-month treatment with sitagliptin on coronary plaque changes in non-culprit lesion in diabetic patients with ACS using serial intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS) analysis., Results: A total of 41 patients were randomly allocated to either sitagliptin group (diet and exercise with sitagliptin 50-100mg daily, n=21) or control group (diet and exercise, n=20) within 72h after percutaneous coronary intervention, and underwent volumetric IVUS and IB-IVUS analyses at baseline and 6-month follow-up. At 6-month follow-up, the percent change in PV as primary endpoint was larger in the sitagliptin group than in the control group, but the difference was not statistically significant (-4.0±8.5% vs. -1.4±8.8%, p=0.35). In IB-IVUS analysis, the percent change in lipid PV significantly decreased in the sitagliptin group compared with the control group (-7.1±21.5% vs. 15.6±41.8%, p=0.03)., Conclusions: Compared with diet and exercise therapy, sitagliptin did not significantly reduce coronary PV in diabetic patients with ACS at 6-month follow-up. However, the percent change in lipid PV significantly decreased in the sitagliptin group, suggesting that sitagliptin has a potential to stabilize the plaque vulnerability., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: High-sensitivity C-reactive protein (hs-CRP) has been used to predict the risk of adverse cardiac events in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Less is known, however, about the association between hs-CRP and long-term outcome after PCI in the Japanese population.Methods and Results:We studied 3,039 all-comer patients with CAD who underwent their first PCI and had data available for preprocedural hs-CRP at Juntendo University between 2000 and 2011. Patients were assigned to tertiles based on preprocedural hs-CRP concentration. We evaluated the incidence of major adverse cardiac events (MACE) including all-cause death, acute coronary syndrome (ACS), and target vessel revascularization (TVR). Patients with higher hs-CRP had a higher prevalence of current smoking, chronic kidney disease and ACS, and a lower prevalence of statin use. During a median follow-up period of 6.5 years, ongoing divergence in MACE with hs-CRP tertile was noted on Kaplan-Meier curves (hs-CRP <0.08 mg/L, 26.4%; 0.08-0.25 mg/L, 38.2%; >0.25 mg/L, 45.6%; log-rank P<0.001). After adjustment for established cardiovascular risk factors, hs-CRP was associated with higher incidence of MACE (hazard ratio [HR], 1.10; 95% CI: 1.04-1.16, P<0.001) and higher all-cause mortality (HR, 1.14; 95% CI: 1.06-1.22, P<0.001)., Conclusions: Preprocedural hs-CRP measurement is clinically useful for long-term risk assessment in Japanese patients with established CAD and undergoing PCI.

Patients with diabetes mellitus (DM) are at twofold to fourfold higher cardiovascular risk than those without DM. Serum levels of lipoprotein(a) (Lp(a)) can be risk factors for adverse events. However, the clinical implications of Lp(a) in patients with DM who underwent percutaneous coronary intervention (PCI) is unknown. The aim of the study was to determine the role of Lp(a) in patients with DM who underwent PCI. A total of 3,508 patients were treated by PCI from 1997 to 2011 at our institution. Among them, we analyzed consecutive 1,546 patients with DM. Eligible 1,136 patients were divided into 2 groups (high Lp(a) [n = 575] and low Lp(a) [n = 561]) by the median of Lp(a) levels. The number of chronic kidney disease, multivessel disease, and the level of LDL-C were higher in the group with high Lp(a) than with low Lp(a). The median follow-up period was 4.7 years. Event rate of all-cause death was same between the 2 groups (p = 0.37). However, cumulative incidence of cardiac death and acute coronary syndrome was significantly higher in the high Lp(a) than in the low Lp(a) group (p = 0.03). Multivariable analysis selected a high Lp(a) level as an independent predictor of cardiac death and acute coronary syndrome (hazard ratio 1.20; 95% confidence interval 1.00 to 1.42; p = 0.04). In conclusion, a high Lp(a) value could be associated with advanced cardiac events after PCI for patients with DM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

It has not been established whether the achievement of optimal medical therapy (OMT) before implantation of a drug-eluting stent has a clinical benefit for patients with stable coronary artery disease (CAD). This study included 3,004 patients with CAD treated with drug-eluting stent from 123 Japanese participating centers. The achievement of OMT was defined as control of blood pressure <130/80 mm Hg, hemoglobin A1c <7.0%, and low-density lipoprotein cholesterol <100 mg/dl. The primary end point was target vessel failure, a composite of death related to the target vessel, myocardial infarction, or clinically driven revascularization at 24 months after stent implantation. Immediately before the procedure, only 548 patients (18.2%) had achieved all 3 target criteria (the achieved OMT group), whereas the remaining 2,456 patients failed to achieve one or more criteria (the non-OMT group). At 24 months, the incidence of target vessel failure was 7.0% in the achieved OMT group versus 10.0% in the non-OMT group (hazard ratio 0.68, 95% CI 0.48 to 0.96, p = 0.03). The incidence of non-Q-wave myocardial infarction was also lower in the achieved OMT group than in the non-OMT group (0.5% vs 1.5%, p = 0.08). Multivariate logistic regression analysis identified that hemoglobin A1c <7.0% was the only protective predictor of 24-month target vessel failure (odds ratio 0.56, 95% CI 0.43 to 0.73, p <0.01). In conclusion, this study demonstrated that in patients with stable CAD scheduled for stent implantation, achievement of OMT before percutaneous coronary intervention significantly reduced subsequent cardiac events. Achievement of OMT is still insufficient in modern clinical practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain., Methods and Results: This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02-3.31, p = 0.0435)., Conclusions: Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)