Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial.

Background: Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. Methods: This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). Findings: Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06-1.69; p = 0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74-1.24; p = 0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C) <70 mg/dL at 1, 2, and 3 years was 74%, 76%, and 73%, respectively, in the combination therapy group, and was significantly higher than that in the high-intensity statin monotherapy group (57%, 62%, and 59%, respectively, all p < 0.001). Discontinuation of lipid-lowering drugs occurred less frequently in the combination group (4.2% vs. 7.6%, p = 0.001). Interpretation: The effects of ezetimibe combination therapy observed in the RACING trial were consistently preserved among patients with ASCVD following PCI. Ezetimibe combination could be considered as a suitable therapeutic strategy to achieve strict control of LDL-C and reduce drug intolerance in patients who underwent PCI. Funding: Hanmi Pharmaceutical, Seoul, South Korea.

Clinical Implication of Hypoxic Liver Injury for Predicting Hypoxic Hepatitis and In-Hospital Mortality in ST Elevation Myocardial Infarction Patients.

PURPOSE: In this study, we aimed to determine the value of hypoxic liver injury (HLI) in the emergency room (ER) for predicting hypoxic hepatitis (HH) and in-hospital mortality in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: 1537 consecutive STEMI patients were enrolled. HLI in the ER was defined as a ≥2-fold increase in serum aspartate transaminase (AST). HH was defined as a ≥20-fold increase in peak serum transaminase. Patients were divided into four groups according to HLI and HH status (group 1, no HLI or HH; group 2, HLI, but no HH; group 3, no HLI, but HH; group 4, both HLI and HH). RESULTS: The incidences of HLI and HH in the ER were 22% and 2%, respectively. In-hospital mortality rates were 3.1%, 11.8%, 28.6%, and 47.1% for groups 1, 2, 3, and 4, respectively. Patients with HLI and/or HH had worse Killip class, higher cardiac biomarker elevations, and lower left ventricular ejection fraction. Multivariate logistic regression analysis showed that HLI in the ER was an independent predictor of HH [odds ratio 2.572, 95% confidence interval (CI) 1.166-5.675, p=0.019]. The predictive value of HLI in the ER for the development of HH during hospitalization was favorable [area under the curve (AUC) 0.737, 95% CI 0.643-0.830, sensitivity 0.548, specificity 0.805, for cut-off value AST >80]. Furthermore, in terms of in-hospital mortality, predictive values of HLI in the ER and HH during hospitalization were comparable (AUC 0.701 for HLI at ER and AUC 0.674 for HH). CONCLUSION: Among STEMI patients, HLI in the ER is a significant predictor for the development of HH and mortality during hospitalization (INTERSTELLAR ClinicalTrials.gov number, NCT02800421).

Comparison of clinical outcomes between multiple antithrombotic therapy versus left atrial appendage occlusion with dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation.

BACKGROUND: Complex antithrombotic regimens are recommended for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation but carry high bleeding risk. HYPOTHESIS: We aimed to evaluate whether left atrial appendage occlusion (LAAO) with dual antiplatelet therapy (DAPT) improve clinical outcomes when compared with multiple antithrombotic therapy (MAT) in patients with AF undergoing DES implantation. METHODS: Among 475 AF patients who underwent DES, 41 patients treated by LAAO with DAPT and 434 patients on MAT were compared. MAT was defined as any combination of warfarin-based antithrombotic therapy. Among the MAT group, 34.8% were on triple antithrombotic therapy. The primary endpoint was a net adverse clinical event (NACE), a composite of cerebrovascular accident (CVA) and major bleeding. Secondary endpoints were CVA, major bleeding, major adverse cardiac and cerebral event (MACCE), MI, cardiovascular death, and all-cause death. Additional analysis between the new oral anticoagulant (NOAC)-based antithrombotic therapy group (n = 45) and the LAAO group was performed for the same endpoints. To adjust the confounding factors, inverse probability of treatment weighting (IPTW) was applied during the endpoint analysis. RESULTS: The LAAO group showed higher incidences of diabetes mellitus, prior CVA, higher CHA2DS2-VASc score (4.56±1.55 vs. 2.96±1.60; P<0.0001), and higher HAS-BLED score (3.24±1.20 vs. 2.13±0.75; P<0.0001). NACE occurred less frequently in the LAAO group than the MAT group at 24 months (9.4% vs. 15.3%; hazard ratio 0.274; 95% confidence interval 0.136 - 0.553; P = 0.0003), mainly driven by the reduction in major bleeding (2.4% vs. 9.3%; hazard ratio 0.119; 95% confidence interval 0.032 - 0.438; P = 0.001). The LAAO group with greater thrombotic and hemorrhagic risks showed comparable primary/secondary outcomes with the NOAC-based anti-thrombotic therapy group. CONCLUSIONS: Among patients with AF who underwent DES implantation, the LAAO group had better net clinical outcomes for preventing CVA and major bleeding than the MAT group. Further large-scale trials including comparisons with NOACs are warranted.

BioMatrix versus Orsiro biodegradable polymer stents in all-comer patients with coronary artery disease: the multicentre, randomised BIODEGRADE trial.

AIMS: The aim of this trial was to compare the safety and efficacy of a thin-strut biodegradable polymer sirolimus-eluting cobalt-chromium stent (Orsiro) to a thick-strut biodegradable polymer biolimus-eluting stent (BioMatrix). METHODS AND RESULTS: This randomised, open-label, non-inferiority trial was conducted among patients undergoing percutaneous coronary intervention. The primary endpoint was target lesion failure (TLF). Between July 2014 and September 2017, we randomly assigned 2,341 patients to BioMatrix stents (n=1,166) or Orsiro stents (n=1,175). We analysed 2,327 patients who completed 18-month follow-up. The mean patient age was 63.5 years, and 1,565 (67.3%) patients presented with acute coronary syndrome. At 18 months, 34 (2.9%) patients with BioMatrix stents and 24 (2.1%) with Orsiro stents experienced TLF (hazard ratio [HR] 0.70, upper limit of one-sided 95% confidence interval: 1.18, p for non-inferiority <0.0001). No significant differences were noted in rates of cardiac death (16 [1.4%] vs 12 [1.0%], p=0.558), target lesion-related myocardial infarction (0 [0%] vs 3 [0.3%], p=0.250), target lesion revascularisation (18 [1.6%] vs 10 [0.9%], p=0.124), or stent thrombosis (0 [0%] vs 2 [0.2%], p=0.50). CONCLUSIONS: In patients with a high prevalence of acute coronary syndrome, Orsiro stents were not inferior to BioMatrix stents. Both showed good clinical outcomes.

Effect of Intravascular Ultrasound-Guided Drug-Eluting Stent Implantation: 5-Year Follow-Up of the IVUS-XPL Randomized Trial.

OBJECTIVES: The goal of this study was to evaluate whether the beneficial effect of use of intravascular ultrasound (IVUS) is sustained for long-term follow-up. BACKGROUND: The use of IVUS promoted favorable 1-year clinical outcome in the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) trial. It is not known, however, whether this effect is sustained for long-term follow-up. METHODS: The IVUS-XPL trial randomized 1,400 patients with long coronary lesions (implanted stent length ≥28 mm) to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. Five-year clinical outcomes were investigated in patients who completed the original trial. The primary outcome was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 5 years, analyzed by intention-to-treat. RESULTS: Five-year follow-up was completed in 1,183 patients (85%). Major adverse cardiac events at 5 years occurred in 36 patients (5.6%) receiving IVUS guidance and in 70 patients (10.7%) receiving angiographic guidance (hazard ratio: 0.50; 95% confidence interval: 0.34 to 0.75; p = 0.001). The difference was driven mainly by a lower risk for target lesion revascularization (31 [4.8%] vs. 55 [8.4%]; hazard ratio: 0.54; 95% confidence interval: 0.33 to 0.89; p = 0.007). By landmark analysis, major adverse cardiac events between 1 and 5 years occurred in 17 patients (2.8%) receiving IVUS guidance and in 31 patients (5.2%) receiving angiographic guidance (hazard ratio: 0.53; 95% confidence interval: 0.29 to 0.95; p = 0.031). CONCLUSIONS: Compared with angiography-guided stent implantation, IVUS-guided stent implantation resulted in a significantly lower rate of major adverse cardiac events up to 5 years. Sustained 5-year clinical benefits resulted from both within 1 year and from 1 to 5 years post-implantation. (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions [IVUS-XPL Study]: Retrospective and Prospective Follow-Up Study; NCT03866486).

Favorable neurological outcome after ischemic cerebrovascular events in patients treated with percutaneous left atrial appendage occlusion compared with warfarin.

OBJECTIVES: This study sought to investigate neurological disability after ischemic cerebrovascular events in patients treated with left atrial appendage (LAA) occlusion compared with those on warfarin. BACKGROUND: Prior studies demonstrated that cerebrovascular events after LAA occlusion in patients with nonvalvular atrial fibrillation (NVAF) is largely nondisabling. METHODS: From the 1,189 patients in the Korean LAA Occlusion and European Amplatzer Cardiac Plug Multi-Center Registry, 24 patients who experienced ischemic cerebrovascular events after LAA occlusion were enrolled. The neurological outcomes were compared with those in 68 patients who experienced an ischemic cerebrovascular event while on warfarin (Yonsei Stroke Registry). A modified Rankin scale (mRS) score of 3-6 categorized the cerebrovascular event as disabling. The mRS at discharge and at 3 and 12 months postcerebrovascular event in the two groups was compared. RESULTS: The percentages of disabling cerebrovascular events were 37.5% and 58.8% at discharge (P = 0.07), 20.8% and 42.6% at 3 months (P = 0.08), and 12.5% and 39.7% at 12 months (P = 0.02) in the LAA occlusion and warfarin groups, respectively. The mRS was significantly lower in the LAA occlusion group at discharge and at 3 months (P < 0.01) and 12 months (P < 0.01) postcerebrovascular event despite no significant difference in mRS before cerebrovascular events (P = 0.98). Patients in the LAA occlusion group demonstrated a significant reduction in mRS between discharge and 12 months (P < 0.01), unlike patients in the warfarin group (P = 0.10). CONCLUSIONS: Ischemic cerebrovascular events in patients who previously underwent percutaneous LAA occlusion for NVAF were more favorable than in patients on warfarin.

Complete Versus Culprit-Only Revascularization for ST-Segment Elevation Myocardial Infarction and Multivessel Disease in the 2nd Generation Drug-Eluting Stent Era: Data from the INTERSTELLAR Registry.

BACKGROUND AND OBJECTIVES: We aimed to compare outcomes of complete revascularization (CR) versus culprit-only revascularization for ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) in the 2nd generation drug-eluting stent (DES) era. METHODS: From 2009 to 2014, patients with STEMI and MVD, who underwent primary percutaneous coronary intervention (PCI) using a 2nd generation DES for culprit lesions were enrolled. CR was defined as PCI for a non-infarct-related artery during the index admission. Major adverse cardiovascular event (MACE) was defined as cardiovascular (CV) death, non-fatal myocardial infarction, target lesion revascularization, or heart failure during the follow-up year. RESULTS: In total, 705 MVD patients were suitable for the analysis, of whom 286 (41%) underwent culprit-only PCI and 419 (59%) underwent CR during the index admission. The incidence of MACE was 11.5% in the CR group versus 18.5% in the culprit-only group (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.37-0.86; p<0.01; adjusted HR, 0.64; 95% CI, 0.40-0.99; p=0.04). The CR group revealed a significantly lower incidence of CV death (7.2% vs. 12.9%; HR, 0.51; 95% CI, 0.31-0.86; p=0.01 and adjusted HR, 0.57; 95% CI; 0.32-0.97; p=0.03, respectively). CONCLUSIONS: CR was associated with better outcomes including reductions in MACE and CV death at 1 year of follow-up compared with culprit-only PCI in the 2nd generation DES era.

Feasibility of Left Atrial Appendage Occlusion for Left Atrial Appendage Thrombus in Patients With Persistent Atrial Fibrillation.

This study sought to investigate the safety of percutaneous left atrial appendage (LAA) occlusion for stroke prevention in patients with nonvalvular atrial fibrillation who have LAA thrombus. From October 2010 to October 2016, LAA occlusions were performed in facilities within a Korean multicenter registry in patients without (n = 132) or with (n = 10) LAA thrombus (detected during preprocedural assessments). The incidences of periprocedural complications, including stroke, pericardial tamponade, major bleeding, and device embolization, were assessed and compared between the groups. The incidence of periprocedural complications was not significantly different between patients with and without LAA thrombus (0% vs 5% [6 of 132]; p = 0.49). During the mean 23.2 ± 17.5-month follow-up duration, 7 major adverse cardiac events occurred (1 cardiovascular death, 6 ischemic strokes), but overall event rates were not significantly different between the groups (14% vs 9%; p = 0.47). In conclusion, percutaneous LAA occlusion in nonvalvular atrial fibrillation patients with LAA thrombus may be a safe and feasible alternative to anticoagulation in select patients at a high risk of bleeding or contraindication to anticoagulation, or in whom anticoagulation failed to prevent stroke.

Safety of six-month dual antiplatelet therapy after second-generation drug-eluting stent implantation: OPTIMA-C Randomised Clinical Trial and OCT Substudy.

AIMS: There are few randomised studies concerning the optimal duration of dual antiplatelet therapy (DAPT) for patients who receive a second-generation drug-eluting stent (DES). This trial aimed to investigate the safety of six-month compared with 12-month DAPT maintenance after second-generation DES implantation. METHODS AND RESULTS: A prospective, randomised, multicentre trial was performed at 10 medical centres. The 1,368 patients included in the study received a biolimus-eluting stent (BES) or a zotarolimus-eluting stent (ZES). The primary outcome measured was the composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), or ischaemia-driven target lesion revascularisation at the 12-month follow-up. The secondary outcome was the percentage of uncovered struts at six months in 60 patients (30 ZES, 30 BES) using optical coherence tomography (OCT) assessment. Each patient was randomly assigned to six-month (n=684) or 12-month DAPT (n=684). Major adverse cardiac events at 12 months occurred in eight patients (1.2%) in the six-month DAPT group and in four patients (0.6%) in the 12-month DAPT group (risk difference 0.6%; 95% confidence interval [CI]: -0.4-1.6%; p=0.24). The upper 95% CI limit was lower than the pre-specified limit of 4% non-inferiority (p for non-inferiority <0.05). The percentage of uncovered struts was 3.16±4.30% at six months in 60 stents of 60 patients. CONCLUSIONS: After second-generation DES implantation, six-month DAPT was not inferior to 12-month DAPT in terms of MACE occurrence over the 12-month follow-up period. OCT examination revealed favourable stent strut coverage at six months after stent implantation.

Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong).

The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], P<0.0001), and the difference was -51.7% (4.1%) (95% confidence interval: -59.8% to -43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (-10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was -10.5 (1.8) mmHg (95% confidence interval: -14.1 to -6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden.

Prognostic Impact of Combined Contrast-Induced Acute Kidney Injury and Hypoxic Liver Injury in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results from INTERSTELLAR Registry.

BACKGROUND: Besides contrast-induced acute kidney injury(CI-AKI), adscititious vital organ damage such as hypoxic liver injury(HLI) may affect the survival in patients with ST-elevation myocardial infarction (STEMI). We sought to evaluate the prognostic impact of CI-AKI and HLI in STEMI patients who underwent primary percutaneous coronary intervention (PCI). METHODS: A total of 668 consecutive patients (77.2% male, mean age 61.3±13.3 years) from the INTERSTELLAR STEMI registry who underwent primary PCI were analyzed. CI-AKI was defined as an increase of ≥0.5 mg/dL in serum creatinine level or 25% relative increase, within 48h after the index procedure. HLI was defined as ≥2-fold increase in serum aspartate transaminase above the upper normal limit on admission. Patients were divided into four groups according to their CI-AKI and HLI states. Major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of all-cause mortality, non-fatal MI, non-fatal stroke, ischemia-driven target lesion revascularization and target vessel revascularization were recorded. RESULTS: Over a mean follow-up period of 2.2±1.6 years, 94 MACCEs occurred with an event rate of 14.1%. The rates of MACCE and all-cause mortality were 9.7% and 5.2%, respectively, in the no organ damage group; 21.3% and 21.3% in CI-AKI group; 18.5% and 14.6% in HLI group; and 57.7% and 50.0% in combined CI-AKI and HLI group. Survival probability plots of composite MACCE and all-cause mortality revealed that the combined CI-AKI and HLI group was associated with the worst prognosis (p<0.0001 for both). CONCLUSION: Combined CI-AKI after index procedure and HLI on admission is associated with poor clinical outcomes in patients with STEMI who underwent primary PCI. (INTERSTELLAR ClinicalTrials.gov number, NCT02800421.).

Left Atrial Appendage Occlusion in Non-Valvular Atrial Fibrillation in a Korean Multi-Center Registry.

BACKGROUND: The aim of this study was to evaluate clinical outcome after left atrial appendage (LAA) occlusion in real clinical practice and compare between Amplatzer cardiac plug (ACP) and Watchman. METHODS AND RESULTS: From October 2010 to February 2015, 96 successful LAA occlusion procedures were performed using either ACP (n=50) or Watchman device (n=46) in non-valvular atrial fibrillation (AF) patients (59 male; age, 65.1±9.4 years; CHADS2, 2.5±1.2; CHA2DS2-VASC, 3.9±1.6; HAS-BLED, 2.7±1.3). The procedure success rate was 96.8%. There were serious complications in 4 patients (4.1%; 2 cardiac tamponade, 1 device embolization, and 1 major bleed). The anticoagulation cessation rate after 6 weeks was 92.7%. During mean 21.9-month follow-up, the incidence of death, stroke, systemic embolization and major bleeding was 5.2%, 4.2%, 0% and 1.0%, respectively. On transesophageal echocardiography of 93 patients within 6 months after the procedure, 24 residual leaks were observed (25.8%; 2 mild, 18 moderate, and 4 major). Clinical outcome was similar for the 2 devices, but peridevice leakage was more frequent with the Watchman than the ACP. CONCLUSIONS: LAA occlusion was feasible in non-valvular AF patients with high risk of stroke and hemorrhage. The ACP and Watchman devices were similar in terms of procedural and clinical outcomes. (Circ J 2016; 80: 1123-1130).

Efficacy and Safety of DP-R202 in Patients with Chronic Artery Occlusive Disease: Multicenter Randomized Double-blind Active-controlled Parallel Group Phase III Clinical Study.

PURPOSE: Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine 2A antagonist, is a widely used antiplatelet agent for the treatment of peripheral arterial disease (PAD). DP-R202 is a new sarpogrelate hydrochloride product with an improved dosage regimen compared with the agent in current use. The aim of this study was to compare the efficacy and safety profile of DP-R202 and Anplag(⁎) Tab in patients with PAD. METHODS: This study was a 12-week, multicenter, randomized, double-blinded, active-controlled, parallel group comparative Phase III clinical trial. One hundred fifty-one volunteer patients with PAD were randomized to receive DP-R202 300 mg once daily or Anplag Table 100 mg TID for 12 weeks. The primary end point was a change in patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. Results after 4, 8, and 12 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. FINDINGS: Two hundred thirty-one patients from 25 medical centers were assessed, and 151 were enrolled and randomly assigned to 1 of 2 treatment groups. Seventy-five patients received DP-R202 300 mg once daily and 76 patients received Anplag Table 100 mg TID for 12 weeks. Analysis of the change in lower leg pain intensity as determined by VAS score between baseline and week 12 (mean [SD], 20.72 [20.06] mm vs 15.55 [21.44] mm) suggested that DP-R202 was not inferior to Anplag Tab, and no significant differences were found in the secondary end points. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. For tolerability, no specific issue was found during the treatment period. IMPLICATION: The results of this study suggest that DP-R202 was not inferior to Anplag Tab for efficacy in patients with PAD and indicated a good safety profile.

Effect of Intravascular Ultrasound-Guided vs Angiography-Guided Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial.

IMPORTANCE: Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE: To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS: The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS: Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS: One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, -2.97% [95% CI, -5.14% to -0.79%]) (hazard ratio [HR], 0.48 [95% CI, 0.28 to 0.83], P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5%]) compared with angiography-guided (33 [5.0%]) stent implantation (HR, 0.51 [95% CI, 0.28 to 0.91], P = .02). Cardiac death and target lesion-related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 [95% CI, 0.14 to 2.52], P = .48). Target lesion-related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE: Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308281.

Clinical Impact of Intravascular Ultrasound-Guided Chronic Total Occlusion Intervention With Zotarolimus-Eluting Versus Biolimus-Eluting Stent Implantation: Randomized Study.

BACKGROUND: There have been no randomized studies comparing intravascular ultrasound (IVUS)-guided versus conventional angiography-guided chronic total occlusion (CTO) intervention using new-generation drug-eluting stent Therefore, we conducted a prospective, randomized, multicenter trial designed to test the hypothesis that IVUS-guided CTO intervention is superior to angiography-guided intervention. METHODS AND RESULTS: After successful guidewire crossing, 402 patients with CTOs were randomized to the IVUS-guided group (n=201) or the angiography-guided group (n=201) and secondarily randomized to Resolute zotarolimus-eluting stents or Nobori biolimus-eluting stents. The primary and secondary end points were cardiac death and a major adverse cardiac event defined as the composite of cardiac death, myocardial infarction, or target-vessel revascularization, respectively. After 12-month follow-up, the rate of cardiac death was not significantly different between the IVUS-guided group (0%) and the angiography-guided group (1.0%; P by log-rank test=0.16). However, major adverse cardiac event rates were significantly lower in the IVUS-guided group than that in the angiography-guided group (2.6% versus 7.1%; P=0.035; hazard ratio, 0.35; 95% confidence interval, 0.13-0.97). Occurrence of the composite of cardiac death or myocardial infarction was significantly lower in the IVUS-guided group (0%) than in the angiography-guided group (2.0%; P=0.045). The rates of target-vessel revascularization were not significantly different between the 2 groups. In the comparison between Resolute zotarolimus-eluting stent and Nobori biolimus-eluting stent, major adverse cardiac event rates were not significantly different (4.0% versus 5.7%; P=0.45). CONCLUSIONS: Although IVUS-guided CTO intervention did not significantly reduce cardiac mortality, this randomized study demonstrated that IVUS-guided CTO intervention might improve 12-month major adverse cardiac event rate after new-generation drug-eluting stent implantation when compared with conventional angiography-guided CTO intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01563952.

Serum transaminase determined in the emergency room predicts outcomes in patients with acute ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention.

BACKGROUND: Elevated serum aspartate and alanine aminotransferase (AST and ALT) are often observed in patients with acute ST-segment elevation myocardial infarction (STEMI) and the condition is ascribed to liver hypoperfusion. We evaluated the prevalence and prognostic implication of hypoxic liver injury (HLI) in STEMI. METHODS: Patients with STEMI and no preexisting liver disease who underwent primary percutaneous coronary intervention (PCI) were enrolled. A blood test was performed at the time of presentation and transthoracic echocardiography was performed after the index PCI. We reviewed medical records and contacted families of the patients by telephone to assess outcomes. RESULTS: Of 456 patients (age 60 ± 13 years, 370 males), 31 patients (7%) died during follow-up (duration: 754 ± 540 days). Those patients were older (72 ± 10 vs. 59 ± 13 years), had higher AST (179 ± 224 vs. 64 ± 103 U/L), ALT (56 ± 79 vs. 35 ± 33 U/L), blood urea nitrogen (25 ± 15 vs. 17 ± 7 mg/dL), uric acid (6.9 ± 2.9 vs. 5.8 ± 1.6 mg/dL), creatine kinase-myocardial band isoenzyme (76 ± 104 vs. 41 ± 79 ng/mL), troponin I (19.9 ± 23.0 vs. 10.8 ± 19.1 ng/mL), and lower albumin (4.0 ± 0.5 vs. 4.2 ± 0.4 g/dL) at the time of presentation (p<0.05 for all). Particularly, AST independently predicted all-cause mortality (per 10 U/L increase, hazard ratio: 1.06, 95% confidence interval: 1.02-1.10, p=0.007), whereas cardiac markers did not. HLI (>2-fold elevation of AST or ALT upper normal limits) showed close correlation with reduced left ventricular ejection fraction (ß=-0.12, p=0.03) and patients with the condition (n=100 [20%]) had poorer survival than the others (Log-Rank, p=0.005). CONCLUSION: The presence of HLI predicts mortality in patients with STEMI who undergo successful primary PCIs.

In vivo imaging of myocardial cell death using a peptide probe and assessment of long-term heart function.

During acute myocardial infarction (AMI), both apoptosis and necrosis of myocardial cells could occur and lead to left ventricular (LV) functional decline. Here we determined whether in vivo imaging signals of myocardial cell death by ApoPep-1 (CQRPPR), a peptide probe that binds to apoptotic and necrotic cells through histone H1, at an early stage after AMI showed correlation with the long-term heart function. AMI was induced using a rat model of ischemia and reperfusion (I/R) injury. Fluorescence-labeled ApoPep-1 was administered by intravenous injection into rats 2h after reperfusion. Ex vivo imaging of hearts isolated 2h after peptide injection showed higher levels of near-infrared fluorescence (NIRF) signals at hearts of I/R rats than those of sham-operated rats. The fluorescent peptide was rapidly cleared from the blood and did not bind to red and white blood cells. Localization of fluorescent ApoPep-1 at the area of cell death was demonstrated by co-staining of myocardial tissue with TUNEL. The intensity of in vivo NIRF imaging signals by homing of ApoPep-1 to injured myocardium of I/R rats obtained 2h after peptide injection (equivalent to 4h after injury) showed strong and moderate correlation with the change in the LV ejection fractions (r(2)=0.82) and the size of the fibrotic area (r(2)=0.64), respectively, observed at four weeks after injury. These results suggest that ApoPep-1-mediated in vivo imaging signals of myocardial cell death, including both apoptosis and necrosis, at an early stage of AMI could be a potential biomarker for assessment of long-term outcome of heart function.

A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation).

OBJECTIVES: The goal of this study was to evaluate shorter duration (3 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation. BACKGROUND: There have been few published reports of prospective randomized clinical studies comparing the safety and efficacy of shorter duration DAPT after DES implantation. METHODS: We randomly assigned 2,117 patients with coronary artery stenosis into 2 groups according to DAPT duration and stent type: 3-month DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3-month DAPT, n=1,059) versus 12-month DAPT following the other DES implantation (standard therapy, n=1,058). We hypothesized that the E-ZES+3-month DAPT would be noninferior to the standard therapy for the primary composite endpoint (cardiovascular death, myocardial infarction, stent thrombosis, target\vessel revascularization, or bleeding) at 1 year. RESULTS: The primary endpoint occurred in 40 (4.7%) patients assigned to E-ZES+3-month DAPT compared with 41 (4.7%) patients assigned to the standard therapy (difference: 0.0%; 95% confidence interval [CI]: -2.5 to 2.5; p=0.84; p<0.001 for noninferiority). The composite rates of any death, myocardial infarction, or stent thrombosis were 0.8% and 1.3%, respectively (difference: -0.5%; 95% CI: -1.5 to 0.5; p=0.48). The rates of stent thrombosis were 0.2% and 0.3%, respectively (difference: -0.1%; 95% CI: -0.5 to 0.3; p=0.65) without its further occurrence after cessation of clopidogrel in the E-ZES+3-month DAPT group. The rates of target vessel revascularization were 3.9% and 3.7%, respectively (difference: 0.2%; 95% CI: -2.3 to 2.6; p=0.70). CONCLUSIONS: E-ZES+3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint. (REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following E-ZES implantation [RESET]; NCT01145079).