Woo Young Chung

Six-Month Versus 12-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents The Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) Randomized, Multicenter Study

Background— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P =0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P =0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P =0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P =0.005) among diabetic patients. Conclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration— URL: . Unique identifier: [NCT00698607][1]. # Clinical Perspective {#article-title-31} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00698607&atom=%2Fcirculationaha%2F125%2F3%2F505.atomBackground— The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results— We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03; P=0.005) among diabetic patients. Conclusions— Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

Everolimus-Eluting Versus Sirolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention The EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) Randomized Trial

OBJECTIVES The goal of this study was to compare the angiographic outcomes of everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in a head-to-head manner. BACKGROUND EES have been shown to be superior to paclitaxel-eluting stents in inhibiting late loss (LL) and clinical outcome. Whether EES may provide similar angiographic and clinical outcomes compared with SES is undetermined. METHODS This was a prospective, randomized, open-label, multicenter trial to demonstrate the noninferiority of EES compared with SES in preventing LL at 9 months. A total of 1,443 patients undergoing percutaneous coronary intervention were randomized 3:1 to receive EES or SES. Routine follow-up angiography was recommended at 9 months. The primary endpoint was in-segment LL at 9 months, and major secondary endpoints included in-stent LL at 9 months, target lesion failure, cardiac death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis at 12 months. Data were managed by an independent management center, and clinical events were adjudicated by an independent adjudication committee. RESULTS Clinical follow-up was available in 1,428 patients and angiographic follow-up in 924 patients (1,215 lesions). The primary endpoint of the study (in-segment LL at 9 months) was 0.11 ± 0.38 mm and 0.06 ± 0.36 mm for EES and SES, respectively (p for noninferiority = 0.0382). The in-stent LL was also noninferior (EES 0.19 ± 0.35 mm; SES 0.15 ± 0.34 mm; p for noninferiority = 0.0121). The incidence of clinical endpoints was not statistically different between the 2 groups, including target lesion failure (3.75% vs. 3.05%; p = 0.53) and stent thrombosis (0.37% vs. 0.83%; p = 0.38). CONCLUSIONS EES were noninferior to SES in inhibition of LL after stenting, which was corroborated by similar rates of clinical outcomes. (Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting [EXCELLENT]; NCT00698607).

Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction (POST) randomized trial.

Background— Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment–elevation myocardial infarction. However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. Methods and Results— We performed a multicenter, prospective, randomized, open-label, blinded end-point trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction within 12 hours after symptom onset were randomly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: The angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure (<6 atm) inflations, each separated by 1 minute of deflation. The primary end point was complete ST-segment resolution (percentage resolution of ST-segment elevation >70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, −1.0%; 95% confidence interval, −8.4 to 6.4; P=0.79). The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4% [P=0.20] and 4.3% versus 3.7% [P=0.70], respectively). Conclusion— Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment–elevation myocardial infarction undergoing primary PCI with current standard practice. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00942500.Background —Ischemic postconditioning has been reported to reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI). However, cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial. Methods and Results —We performed a multicenter, prospective, randomized, open-label, blinded endpoint trial. A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) for STEMI within 12 hours after symptom onset were randomly assigned to the postconditioning group or the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow as follows: the angioplasty balloon was positioned at the culprit lesion, and inflated 4 times for 1 minute with low-pressure ( 70%) measured at 30 minutes after PCI. Complete ST-segment resolution occurred in 40.5% of patients in the postconditioning group and 41.5% of patients in the conventional PCI group (absolute difference, -1.0%; 95% confidence interval, -8.4% to 6.4%; P =0.79). The rate of myocardial blush grade of 0 or 1 and the major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group (17.2% versus 22.4%, P =0.20, and 4.3% versus 3.7%, P =0.70, respectively). Conclusions —Ischemic postconditioning did not improve myocardial reperfusion in patients with STEMI undergoing primary PCI with current standard practice. Clinical Trial Registration Information —http://ClinicalTrials.gov. Identifier: [NCT00942500][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00942500&atom=%2Fcirculationaha%2Fearly%2F2013%2F09%2F25%2FCIRCULATIONAHA.113.001690.atom

Usefulness of coronary pressure measurement for functional evaluation of drug-eluting stent restenosis.

Despite the widespread adoption of drug-eluting stent (DES) implantation, the optimal treatment of DES failures remains challenging. The present study evaluated the relation between quantitative angiography and the fractional flow reserve (FFR) in restenotic lesions after DES implantation and the efficacy of FFR in determining whether to treat these lesions. To assess their functional significance, the coronary pressure-derived FFR was measured in 50 DES restenotic lesions (49 patients). Additional intervention was performed in lesions with a FFR <0.8. Major adverse cardiac events were assessed at 12 months after the reintervention procedure. The mean percent diameter stenosis (%DS) was 58 ± 13%. Of the 50 lesions, 20 (40%) were deferred without additional intervention. The FFR and %DS had a negative correlation (r = -0.61, p <0.001). However, when only the lesions with diffuse-type restenosis (15 lesions) were analyzed, the degree of correlation decreased (r = -0.56, p = 0.12). Although most lesions (89%) with a %DS of ≥70 had significant functional ischemia, among 41 lesions with a %DS <70, only 20 (49%) had demonstrated functional patency. The incidence of adverse events during the 12 months of follow-up after FFR-guided treatment was 18.0% (23.3% in the FFR <0.80 group and 10.0% in FFR ≥0.80 group). In conclusion, a discrepancy was found between functional ischemia measured by the FFR and the angiographic %DS, in particular, in moderate- or diffuse-type restenotic lesions after DES implantation. The outcome of FFR-guided deferral in patients with DES in-stent restenosis seems favorable.

Paclitaxel- Versus Sirolimus-Eluting Stents for Treatment of ST-Segment Elevation Myocardial Infarction: With Analyses for Diabetic and Nondiabetic Subpopulation

OBJECTIVES The aim of this study was to determine which drug-eluting stent (DES) is preferable for the treatment of ST-segment elevation myocardial infarction (STEMI) and to elucidate the impact of diabetes mellitus on the outcome of each DES. BACKGROUND Recent studies have shown the benefit of DES in patients with STEMI. Diabetes mellitus might differentially affect outcomes of each DES. METHODS We analyzed the large-scale, prospective, observational KAMIR (Korea Acute Myocardial Infarction Registry) study, which enrolled 4,416 STEMI patients (26% with diabetes) treated with paclitaxel-eluting stent (PES) or sirolimus-eluting stent (SES). Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization (TLR). RESULTS In the overall population, the MACE rate at 1 year was significantly higher in the PES than the SES group (11.6% vs. 8.6%, p = 0.014), which was mainly due to increased TLR (3.7% vs. 1.8%, p < 0.001). In the diabetic subgroup, however, the MACE rate was not significantly different between PES and SES (14.5% vs. 12.3%, p = 0.217), in contrast to the nondiabetic subgroup, where PES was inferior to SES as in the overall population. Matching by propensity-score did not significantly alter these results. For TLR, there was interaction between the type of stents and diabetes mellitus (unadjusted: p = 0.052; after propensity-score matching: p = 0.035). CONCLUSIONS The PES was inferior to the SES in the overall population, with regard to the occurrence of MACE and TLR. However, subgroup analysis for diabetic subjects showed no differences in clinical outcomes between PES and SES. These results suggest that diabetes differentially affects the outcome of first-generation DES.

Long-Term Clinical Outcomes of Fractional Flow Reserve–Guided Versus Routine Drug-Eluting Stent Implantation in Patients With Intermediate Coronary Stenosis Five-Year Clinical Outcomes of DEFER-DES Trial

Background—We aimed to compare the long-term clinical outcomes between fractional flow reserve (FFR)–guided and routine drug-eluting stent (DES) implantation in patients with an intermediate coronary stenosis. Methods and Results—A total of 229 patients with an angiographically intermediate coronary stenosis were randomly assigned to FFR-guided or Routine-DES implantation group. For FFR-guided group (n=114), treatment strategy was determined according to the target vessel FFR (FFR<0.75: DES implantation [FFR-DES group]; FFR≥0.75: deferral of stenting [FFR-Defer group]). Routine-DES group underwent DES implantation without FFR measurement (n=115). The primary end point was the incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and target lesion revascularization. Of lesions assigned to FFR-guided strategy, only one quarter had functional significance (FFR<0.75). At 2-year follow-up, the cumulative incidence of major adverse cardiac events was 7.9±2.5% in the FFR-guided group and 8.8±2.7% in Routine-DES group (P=0.80). At 5-year follow-up, the cumulative incidence of major adverse cardiac events was 11.6±3.0% and 14.2±3.3% for the FFR-guided group and the Routine-DES group (P=0.55). There was no difference in major adverse cardiac events rates between the 2 groups ⩽5-year follow-up (hazard ratio, 1.25; 95% confidence interval, 0.60–2.60). Conclusions—In lesions with angiographically intermediate stenosis, FFR guidance provides a tailored approach, which is at least as good as an angiography-guided routine-DES implantation strategy and avoids unnecessary DES-stenting in a considerable part of the patients. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00592228.

Long-term effects of ischemic postconditioning on clinical outcomes: 1-year follow-up of the POST randomized trial

BACKGROUND In the Effects of Postconditioning on Myocardial Reperfusion in Patients with ST-segment Elevation Myocardial Infarction (POST) trial, ischemic postconditioning failed to improve myocardial reperfusion. However, long-term effects of ischemic postconditioning on clinical outcomes are not known in patients with ST-segment elevation myocardial infarction. METHODS A total of 700 patients undergoing primary percutaneous coronary intervention (PCI) were randomly assigned to the postconditioning group or the conventional primary PCI group in a 1:1 ratio. Postconditioning was performed immediately after restoration of coronary flow by balloon occlusion 4 times for 1 minute. Complete follow-up data for major clinical events at 1 year were available in 695 patients (99.3%), and analyses were done by the intention to treat principle. The primary outcome was a composite of death, myocardial infarction, severe heart failure, or stent thrombosis at 1 year. RESULTS At 1 year, a composite of death, myocardial infarction, severe heart failure, or stent thrombosis occurred in 21 patients (6.1%) in the postconditioning group and 16 patients (4.6%) in the conventional PCI group (hazard ratio [HR] 1.32, 95% CI 0.69-2.53, P = .40). The risk of death (4.9% vs 3.7%, HR 1.32, 95% CI 0.64-2.71, P = .46), heart failure (2.6% vs 2.3%, HR 1.13, 95% CI 0.44-2.94, P = .80), and stent thrombosis (2.3% vs 1.7%, HR 1.34, 95% CI 0.46-3.85, P = .59) did not differ significantly between the 2 groups. CONCLUSIONS Ischemic postconditioning does not seem to improve the 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing primary PCI.

Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

Background and Objectives There is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI. Subjects and Methods Seventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinase-myocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI. Results The baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001). Conclusion Pre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS.

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial.

BackgroundThere have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stents flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting.Methods/DesignThe primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound.DiscussionThis trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions.Trial registrationRegistered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803).

Angiographic and clinical comparison of novel Orsiro Hybrid sirolimus-eluting stents and Resolute Integrity zotarolimus-eluting stents in all-comers with coronary artery disease (ORIENT trial): study protocol for a randomized controlled trial

BackgroundThe Orsiro Hybrid sirolimus-eluting stent is a newly developed third-generation drug-eluting stent, featuring a unique dual-polymer mix. An active bioabsorbable polymer delivers the anti-proliferative drug, sirolimus, via controlled release, while a passive biocompatible polymeric coating shields the metallic strut from surrounding tissue, preventing interaction. To date, the Orsiro Hybrid sirolimus-eluting stent has excelled in terms of late lumen loss at 9 months in a first-in-man single-arm trial. However, the efficacy and safety data for Orsiro Hybrid sirolimus-eluting stents in a broader population of all-comers are limited. The present study offers an angiographic and clinical comparison of the Orsiro Hybrid sirolimus-eluting stent and the Resolute Integrity zotarolimus-eluting stent in the treatment of patients with coronary artery disease.Methods/designThe ORIENT trial is a multicenter, randomized, open-label, parallel-arm study designed to demonstrate the non-inferiority of the Orsiro Hybrid sirolimus-eluting stent relative to the Resolute Integrity zotarolimus-eluting stent. A total of 375 patients with a spectrum of coronary artery disease will undergo prospective, random assignment to a Orsiro Hybrid sirolimus-eluting stent or Resolute Integrity zotarolimus-eluting stent (2:1 ratio), for a primary endpoint of in-stent late lumen loss at 9 months by quantitative coronary angiography. Secondary 12-month clinical endpoints are death, target lesion revascularization, target vessel revascularization, myocardial infarction, stent thrombosis and target lesion failure (a composite of cardiac death, target lesion revascularization and target vessel-related myocardial infarction).DiscussionThe ORIENT trial is the first study to date comparing the Orsiro Hybrid sirolimus-eluting stent with the Resolute Integrity zotarolimus-eluting stent for efficacy and safety in a population of all-comers with coronary artery disease.Trial registrationClinicaltrials.gov NCT01826552