Eun Seok Shin

Adjunctive cilostazol versus double-dose clopidogrel after drug-eluting stent implantation: the HOST-ASSURE randomized trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety & Effectiveness of Drug-Eluting Stents & Anti-platelet Regimen).

OBJECTIVES This study sought to test the noninferiority of triple antiplatelet therapy (TAT) versus double-dose clopidogrel dual antiplatelet therapy (DDAT) in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Antiplatelet regimen is an integral component of medical therapy after PCI. A 1-week duration of doubling the dose of clopidogrel was shown to improve outcome at 1 month compared with the conventional dose in patients with acute coronary syndrome undergoing PCI. Yet in Asia, the addition of cilostazol is used more commonly than DDAT in high-risk patients. METHODS We randomly assigned 3,755 all-comers undergoing PCI to either TAT or DDAT, which was continued for 1 month, to test the noninferiority of TAT versus DDAT. The primary outcome was the cumulative incidence of net clinical outcome at 1 month post-PCI defined as the composite of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO (Platelet Inhibition and Patient Outcomes) major bleeding. RESULTS TAT was noninferior to DDAT with respect to the primary outcome, which occurred in 1.2% and 1.4% of patients, respectively (-0.22% absolute difference, 0.34% 1-sided 97.5% confidence interval, p = 0.0007 for noninferiority; hazard ratio: 0.85; 95% confidence interval: 0.49 to 1.48; p = 0.558 for superiority). The individual risks of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO major bleeding did not differ significantly between the 2 groups. There were no significant between-group differences in the treatment effect with regard to the rate of the primary outcome. CONCLUSIONS The adjunctive use of cilostazol was noninferior to doubling the dose of clopidogrel for 1 month in all-comers undergoing PCI with exclusively drug-eluting stents. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734).

A comparison of the distribution of necrotic core in bifurcation and non-bifurcation coronary lesions: an in vivo assessment using intravascular ultrasound radiofrequency data analysis.

AIMS High-risk plaques are prone to develop at the site of coronary vessel bifurcations. The distribution of necrotic core at bifurcation lesions (BL) is known, however, little has been described on the necrotic core distribution in non-BLs. Therefore we compared the distribution of necrotic core between BL and non-BLs in coronary arteries using IVUS-VH imaging. METHODS AND RESULTS A total of 129 patients (112 non-BL and 108 BL) were included. The lesions were divided into upstream and downstream segments according the location of the minimum lumen area (MLA) within the plaque. In BLs, compositional analysis showed no differences between the three segments. The necrotic core in contact with the lumen that was located in the downstream segment was significantly larger. While in non-BLs, this was not significantly different between segments. Plaque burden in BLs was 56.60±5.79% vs. 55.50±4.54% in non-BLs, p=0.04. Mean necrotic core area was larger in BLs 0.84±0.55mm2 vs. 0.70±0.49mm2, p=0.048. Mean percentage necrotic core was 15.48±8.02% vs. 14.51±7.64%, p=0.37. There was a trend towards a greater content of necrotic core in contact with the lumen in BLs. The percentage of frames with a major confluent pool of necrotic core in contact with the lumen >10% in BLs was 11.78±17.18 vs. 8.95±17.86 in non-BLs, p=0.065. There was a statistically significant difference in the frequency of IVUS derived thin capped fibroatheromas between bifurcation lesions 20 vs. 13 in non-bifurcation lesions, p=0.03. CONCLUSIONS Bifurcation lesions appear to have a larger plaque burden with a different plaque composition compared to non-bifurcation lesions. This may partly explain the adverse outcomes seen following treatment of bifurcation lesions in contemporary practice.

Fractional flow reserve and pressure-bounded coronary flow reserve to predict outcomes in coronary artery disease

Aims Fractional flow reserve (FFR) has proven to its prognostic and therapeutic value. However, the additive prognostic value of coronary flow reserve (CFR) remains unclear. This study sought to investigate the clinical utility of combined FFR and CFR measurements to predict outcomes. Methods and results Using the prospective, multicentre Interventional Cardiology Research Incooperation Society-FFR registry, a total of 2088 lesions from 1837 patients were included in this substudy. Based on baseline and hyperaemic pressure gradients, we computed physiologic limits of CFR [the so called pressure-bounded (pb) CFR] and classified lesions as low (<2) or high (≥2). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction, and revascularization) analysed on a per-patient basis. During a median follow-up of 1.9 years (inter-quartile range: 1.0-3.0 years), MACE occurred in 5.7% of patients with FFR ≤0.80 vs. 2.8% of patients with FFR >0.80 [adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19-3.89; P = 0.011. In contrast, the incidence of MACE did not differ between patients with pb-CFR < 2 vs. pb-CFR ≥ 2 (4.2% vs. 4.2%; aHR: 0.98, CI: 0.60 to 1.58; P = 0.92). Incorporation of FFR significantly improved model prediction of MACE (global χ2 38.8-48.1, P = 0.002). However, pb-CFR demonstrated no incremental utility to classify outcomes (global χ2 48.1-48.2, P > 0.99). Conclusions In this large, prospective registry of over 2000 coronary lesions, FFR was strongly associated with clinical outcomes. In contrast, a significant association between pb-CFR and clinical events could not be determined and adding knowledge of pb-CFR did not improve prognostication over FFR alone.

Comparison of Paclitaxel-Coated Balloon Treatment and Plain Old Balloon Angioplasty for De Novo Coronary Lesions

Purpose This study compared the angiographic outcomes of paclitaxel-coated balloon (PCB) versus plain old balloon angioplasty (POBA) treatment for de novo coronary artery lesions. At present, there is no available data comparing the efficacy of PCB versus POBA for the treatment of de novo coronary lesions. Materials and Methods This multicenter retrospective observational study enrolled patients with de novo coronary lesions with a reference vessel diameter between 2.5 mm and 3.0 mm and lesion length ≤24 mm who were successfully treated with PCB or POBA. Angiographic measurements and quantitative coronary analysis were performed before and after the procedure, and at 9 months follow-up. Results A total of 72 patients (49 receiving PCB and 23 receiving POBA) were enrolled in this study. Late luminal loss was -0.12±0.30 mm in the PCB group and 0.25±0.50 mm in the POBA group (p<0.001). There was a higher percentage of binary restenosis (diameter stenosis ≥50%) in POBA, compared to PCB (30.4%, n=7 vs. 4.1%, n=2, p<0.001). Target vessel revascularization was higher in the POBA group (13.0%, n=3 vs. 0%, p=0.033). Conclusion PCB treatment of de novo coronary lesions showed better 9-month angiographic outcomes than POBA treatment alone.

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. METHODSANDRESULTS 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).

Early differential changes in coronary plaque composition according to plaque stability following statin initiation in acute coronary syndrome: classification and analysis by intravascular ultrasound-virtual histology.

Purpose The aim of this study was to demonstrate the early effects of statin treatment on plaque composition according to plaque stability on Intravascular Ultrasound-Virtual Histology at 6 months after a coronary event. Previous trials have demonstrated that lipid lowering therapy with statins decreases plaque volume and increases plaque echogenicity in patients with coronary artery disease. Materials and Methods Fifty-four patients (54 lesions) with acute coronary syndrome were prospectively enrolled. We classified and analyzed the target plaques into two types according to plaque stability: thin-cap fibroatheroma (TCFA, n=14) and non-TCFA (n=40). The primary end point was change in percent necrotic core in the 10-mm subsegment with the most disease. Results After 6 months of statin therapy, no change was demonstrated in the mean percentage of necrotic core (18.7±8.5% to 20.0±11.0%, p=0.38). There was a significant reduction in necrotic core percentage in patients with TCFA (21.3±7.2% to 14.4±8.9%, p=0.017), but not in patients with non-TCFA. Moreover, change in percent necrotic core was significantly correlated with change in high-sensitivity C-reactive protein levels (r=0.4, p=0.003). Changes in low-density lipoprotein cholesterol levels and lipid core percentage demonstrated no significant associations. Conclusion A clear reduction of lipid core was observed only for the TCFA plaque type, suggesting that changes in plaque composition following statin therapy might occur earlier in vulnerable plaque than in stable plaque; the effect may be related to the anti-inflammatory effects of statins.

Efficacy and Safety of 30-Mg Fimasartan for the Treatment of Patients With Mild to Moderate Hypertension: An 8-Week, Multicenter, Randomized, Double-Blind, Phase III Clinical Study

PURPOSE The standard 60-mg dose of fimasartan, a newly developed selective angiotensin II receptor blocker, is effective and safe for use in patients with mild to moderate hypertension. This study aimed to compare the efficacy and safety of low-dose (30 mg) fimasartan and placebo or valsartan (80 mg) for 8 weeks in patients with mild to moderate hypertension. METHODS In this randomized trial, 293 patients (219 men; mean age, 54.24 [9.77] years) with mild to moderate hypertension were enrolled. After randomization to receive 30-mg fimasartan (n = 115), placebo (n = 117), or 80-mg valsartan (n = 61), the treatment dose was kept constant without dose escalation for 8 weeks. The primary end point was improvement in sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks that was compared between treatments with low-dose fimasartan and placebo. The secondary end point was the overall efficacy and safety of low-dose fimasartan compared with that of placebo or valsartan. FINDINGS At week 8, SiDBP changed by -9.93 (8.86) mm Hg in the fimasartan group and by -2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy (P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (-9.96 [7.73] vs -2.27 [7.85] mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (-16.18 [14.44] vs -1.95 [13.48] mmHg; P < 0.0001) and at week 8 as determined by SiSBP (-15.35 [16.63] vs -2.30 [14.91] mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, -9.96 [7.73] vs -6.53 [9.58] mm Hg [P = 0.0123]; SiSBP, -16.18 [14.4] vs -7.65 [12.89] mm Hg [P = 0.0002]) and at week 8 (SiDBP, -9.93 [8.86] vs -5.47 [8.96] mm Hg [P = 0.0021]; SiSBP, -15.35 [16.63] vs -7.49 [13.68] mm Hg [P = 0.0021]). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences. IMPLICATIONS Low-dose fimasartan (30 mg) was well tolerated during the study period with no significant TEAEs. Low-dose fimasartan had an effective blood pressure-lowering effect that was greater than that of 80-mg valsartan in patients with mild to moderate hypertension. ClinicalTrials.gov identifier: NCT01672476.

Serial Morphological Changes of Side-Branch Ostium after Paclitaxel-Coated Balloon Treatment of De Novo Coronary Lesions of Main Vessels

Purpose The effects on the side-branch (SB) ostium, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions of main vessels have not been previously investigated. This study was aimed at evaluating the serial morphological changes of the SB ostium after PCB treatment of de novo coronary lesions of main vessels using optical coherence tomography (OCT). Materials and Methods This prospective, single-center observational study enrolled patients with de novo lesions, which were traversed by at least one SB (≥1.5 mm) and were treated with PCB. The SB ostium was evaluated with serial angiographic and OCT assessments pre- and post-procedure, and at 9-months follow-up. Results Sixteen main vessel lesions were successfully treated with PCB, and 26 SBs were included for analysis. Mean SB ostial lumen area increased at 9-months follow-up (0.92±0.68 mm2 pre-procedure, 1.03±0.77 mm2 post-procedure and 1.42±1.18 mm2 at 9-months). The SB ostial lumen area gain was 0.02±0.24 mm2 between pre- and post-procedure, 0.37±0.64 mm2 between post-procedure and 9-months, and 0.60±0.93 mm2 between pre-procedure and 9-months. The ostial lumen area increased by 3.9% [interquartile range (IQR) of -33.3 to 10.4%] between pre- and post-procedure, 52.1% (IQR of -0.7 to 77.3%) between post-procedure and 9-months and 76.1% (IQR of 18.2 to 86.6%) between pre-procedure and 9-months. Conclusion PCB treatment of de novo coronary lesions of main vessels resulted in an increase in the SB ostial lumen area at 9-months.

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.

A Randomized, Double-Blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Fimasartan/Amlodipine Combined Therapy Versus Fimasartan Monotherapy in Patients With Essential Hypertension Unresponsive to Fimasartan Monotherapy.

PURPOSE The goal of this study was to evaluate whether the blood pressure-lowering efficacy of fimasartan/amlodipine combination therapy was superior to that of fimasartan monotherapy after 8 weeks of treatment in patients with hypertension who had failed to respond adequately to fimasartan monotherapy. METHODS This trial was a randomized, double-blind, multicenter, Phase III clinical study. Patients who failed to respond after 4 weeks of treatment with 60 mg daily of fimasartan (sitting systolic blood pressure [SiSBP]) ≥140 mm Hg) were randomized to receive either daily fimasartan 60 mg or fimasartan/amlodipine 60 mg/10 mg. The primary efficacy end point was the change in SiSBP from baseline to week 8. Secondary end points included the change in SiSBP from baseline to week 4, the changes in sitting diastolic blood pressure from baseline to weeks 4 and 8, and the response rate (SiSBP <140 mm Hg or decrease in SiSBP ≥20 mm Hg) or control rate (SiSBP <140 mm Hg) at week 8. Treatment-emergent adverse events were also assessed. FINDINGS Of 143 patients randomized to treatment, 137 patients who had available efficacy data were analyzed. The mean age of patients was 59.1 (8.9) years, and 100 (73.0%) were male. Baseline SiSBP and sitting diastolic blood pressure were 150.6 (9.2) mm Hg and 91.7 (8.6) mm Hg, respectively. In the fimasartan/amlodipine combination group, a greater reduction in SiSBP from baseline to week 8 was observed compared with the fimasartan group (7.8 [13.3] mm Hg in the fimasartan group vs 20.5 [14.6] mm Hg in the fimasartan/amlodipine group; P < 0.0001). This reduction was observed after 4 weeks. The mean SiSBP changes from baseline to week 4 were 8.1 (15.8) mm Hg in the fimasartan group and 20.1 (14.7) mm Hg in the fimasartan/amlodipine group (P < 0.0001). At week 8, the response rate was significantly higher in the fimasartan/amlodipine (82.1%) group than in the fimasartan (32.9%) group (P < 0.0001). The control rate at week 8 was also higher in the fimasartan/amlodipine (79.1%) group than in the fimasartan (31.4%) group (P < 0.0001). Adverse drug reactions were observed in 9 patients (6.3%), with no significant differences between treatment groups. There were no serious adverse events associated with the study drugs. IMPLICATIONS Fimasartan/amlodipine combination therapy exhibited superior efficacy in reducing blood pressure, with no increase in adverse drug reactions, compared with fimasartan monotherapy. ClinicalTrials.gov identifier: NCT02152306.