Sung Cheol Yun

Duration of dual antiplatelet therapy after implantation of drug-eluting stents.

BACKGROUND The potential benefits and risks of the use of dual antiplatelet therapy beyond a 12-month period in patients receiving drug-eluting stents have not been clearly established. METHODS In two trials, we randomly assigned a total of 2701 patients who had received drug-eluting stents and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of myocardial infarction or death from cardiac causes. Data from the two trials were merged for analysis. RESULTS The median duration of follow-up was 19.2 months. The cumulative risk of the primary outcome at 2 years was 1.8% with dual antiplatelet therapy, as compared with 1.2% with aspirin monotherapy (hazard ratio, 1.65; 95% confidence interval [CI], 0.80 to 3.36; P=0.17). The individual risks of myocardial infarction, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause did not differ significantly between the two groups. However, in the dual-therapy group as compared with the aspirin-alone group, there was a nonsignificant increase in the composite risk of myocardial infarction, stroke, or death from any cause (hazard ratio, 1.73; 95% CI, 0.99 to 3.00; P=0.051) and in the composite risk of myocardial infarction, stroke, or death from cardiac causes (hazard ratio, 1.84; 95% CI, 0.99 to 3.45; P=0.06). CONCLUSIONS The use of dual antiplatelet therapy for a period longer than 12 months in patients who had received drug-eluting stents was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction or death from cardiac causes. These findings should be confirmed or refuted through larger, randomized clinical trials with longer-term follow-up. (ClinicalTrials.gov numbers, NCT00484926 and NCT00590174.)

Randomized Trial of Stents versus Bypass Surgery for Left Main Coronary Artery Disease

BACKGROUND Percutaneous coronary intervention (PCI) is increasingly used to treat unprotected left main coronary artery stenosis, although coronary-artery bypass grafting (CABG) has been considered to be the treatment of choice. METHODS We randomly assigned patients with unprotected left main coronary artery stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups. RESULTS The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG (cumulative event rate, 8.7% vs. 6.7%; absolute risk difference, 2.0 percentage points; 95% confidence interval [CI], -1.6 to 5.6; P=0.01 for noninferiority). By 2 years, the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group (cumulative event rate, 12.2% vs. 8.1%; hazard ratio with PCI, 1.50; 95% CI, 0.90 to 2.52; P=0.12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; hazard ratio, 0.92; 95% CI, 0.43 to 1.96; P=0.83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group (cumulative event rate, 9.0% vs. 4.2%; hazard ratio, 2.18; 95% CI, 1.10 to 4.32; P=0.02). CONCLUSIONS In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive. (Funded by the Cardiovascular Research Foundation, Seoul, Korea, and others; PRECOMBAT ClinicalTrials.gov number, NCT00422968.).

Trial of Everolimus-Eluting Stents or Bypass Surgery for Coronary Disease

BACKGROUND Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents. METHODS We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups. RESULTS After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG. CONCLUSIONS Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).

Comparison of Zotarolimus-Eluting Stents With Sirolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization The ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) Randomized Trial

OBJECTIVES The aim of this study was to evaluate the relative efficacy and safety of zotarolimus-eluting stents (ZES) in comparison with the established and widely used sirolimus- (SES) and paclitaxel-eluting stents (PES) in routine clinical practice. BACKGROUND Whether ZES might provide similar clinical and angiographic outcomes in a broad spectrum of patients compared with SES or PES is undetermined. METHODS We performed a single-blind, multicenter, prospectively randomized trial to compare ZES with SES and PES in 2,645 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (MACE) (death, myocardial infarction, and ischemia-driven target vessel revascularization) at 12 months. A noninferiority comparison (ZES vs. SES) and a superiority comparison (ZES vs. PES) were performed for the primary end point. RESULTS Baseline clinical and angiographic characteristics were similar in the 3 groups. At 12 months, the ZES group showed noninferior rates of MACE compared with the SES group (10.2% vs. 8.3%, p for noninferiority = 0.01, p for superiority = 0.17) and significantly fewer MACE than the PES group (10.2% vs. 14.1%, p for superiority = 0.01). The incidence of death or myocardial infarction was similar among the groups (ZES vs. SES vs. PES, 5.8% vs. 6.9% vs. 7.6%, respectively, p = 0.31). The incidence of stent thrombosis was significantly lower in the SES group (ZES vs. SES vs. PES, 0.7% vs. 0% vs. 0.8%, respectively, p = 0.02). CONCLUSIONS In this large-scale, practical randomized trial, the use of ZES resulted in similar rates of MACE compared with SES and in fewer MACE compared with PES at 12 months. (Comparison of the Efficacy and the Safety of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions; NCT00418067).

Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease 5-Year Outcomes of the PRECOMBAT Study

BACKGROUND In a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year. OBJECTIVES This study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis. METHODS We randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis. RESULTS At 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012). CONCLUSIONS During 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968).

Comparison of the Efficacy and Safety of Zotarolimus-, Sirolimus-, and Paclitaxel-Eluting Stents in Patients With ST-Elevation Myocardial Infarction

Drug-eluting stents (DESs) are increasingly used for treatment of acute ST-segment elevation myocardial infarction (STEMI), but there are few comparisons of outcomes of various types of DES. We compared the efficacy and safety of zotarolimus-eluting stents (ZESs), sirolimus-eluting stents (SESs), and paclitaxel-eluting stents (PESs) in primary intervention for STEMI. This multicenter, prospectively randomized ZEST-AMI trial included 328 patients at 12 medical centers who were randomly assigned to ZES (n = 108), SES (n = 110), or PES (n = 110) deployment. The primary end point was major adverse cardiac events (death, MI, and ischemia-driven target vessel revascularization) at 12 months. Secondary end points included the individual components of the primary end point, late loss, angiographic restenosis, and stent thrombosis. Baseline clinical and angiographic characteristics were well matched. In-segment late loss (0.28 +/- 0.42 vs 0.46 +/- 0.48 vs 0.47 +/- 0.50 mm, respectively, p = 0.029) and restenosis rate (2.7% vs 15.9% vs 12.3%, respectively, p = 0.027) at 8 months were lowest in the SES group compared to the ZES and PES groups. At 12 months, cumulative incidence rates of primary end points in the ZES, SES, and PES groups were 11.3%, 8.2%, and 8.2%, respectively (p = 0.834). There were 2 acute (in the SES group) and 5 subacute (2 in the SES group and 3 in the PES group) stent thromboses. Incidence of death, recurrent MI, or ischemia-driven target vessel revascularization did not differ among the 3 groups. In conclusion, despite the difference in restenosis rate, the efficacy and safety of the 3 different DESs showed similar, acceptable results in the treatment of STEMI.

Meta-Analysis of First-Line Triple Therapy for Helicobacter pylori Eradication in Korea: Is It Time to Change?

Proton pump inhibitor (PPI)-based triple therapy consisting of PPI, amoxicillin, and clarithromycin, is the recommended first-line treatment for Helicobacter pylori infection. However, the eradication rate of triple therapy has declined over the past few decades. We analyzed the eradication rate and adverse events of triple therapy to evaluate current practices in Korea. A comprehensive literature search was performed up to August 2013 of 104 relevant studies comprising 42,124 patients. The overall eradication rate was 74.6% (95% confidence interval [CI], 72.1%-77.2%) by intention-to-treat analysis and 82.0% (95% CI, 80.8%-83.2%) by per-protocol analysis. The eradication rate decreased significantly from 1998 to 2013 (P < 0.001 for both intention-to-treat and per-protocol analyses). Adverse events were reported in 41 studies with 8,018 subjects with an overall incidence rate of 20.4% (95% CI, 19.6%-21.3%). The available data suggest that the effectiveness of standard triple therapy for H. pylori eradication has decreased to an unacceptable level. A novel therapeutic strategy is warranted to improve the effectiveness of first-line treatment for H. pylori infection in Korea. Graphical Abstract

Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus-Colonized Neonates in the Neonatal Intensive Care Unit

Background: Methicillin-resistent Staphylococcus aureus (MRSA) colonization can persist for prolonged periods, and patient-related factors are associated with persistent carriage in adults. However, such knowledge is lacking among neonates. Objectives: To better understand the outcome of MRSA-colonized neonates in the neonatal intensive care unit (NICU), we prospectively followed all colonized neonates until decolonization over 39 months and determined the incidence, duration of colonization, clinical outcomes and risk factors associated with prolonged carriage of MRSA. Methods: Nasal and inguinal cultures were obtained from all newly admitted neonates following an outbreak of MRSA. Weekly and 1–2 monthly cultures were obtained from all hospitalized and discharged neonates colonized with MRSA, respectively, until 2 consecutive cultures were negative. Results: 152 of 1,456 (10.4%) neonates became colonized. The mean time to acquire MRSA colonization was 17.1 ± 40.7 (range 1–471) days. The median time to decolonization was 36 days. About 20% of decolonized patients had been colonized for a prolonged period of ≧160 days. 47.5% of colonized patients were sent home colonized, and none with prolonged carriage developed MRSA-related infections in the following 6 months in contrast to 6 infants (3.9%) who developed MRSA sepsis during hospitalization. The only risk factor associated with prolonged carriage was the concurrent colonization of both the inguinal and nasal areas on admission. Conclusion:Nearly all neonates with acquired colonization became decolonized either prior to or after discharge from NICU. A significant percentage failed to decolonize prior to hospital discharge, but almost all decolonized by 30 months in the community without evidence of systemic or local infections.

Mitral valve replacement with or without a concomitant Maze procedure in patients with atrial fibrillation

Background Although the Maze procedure is regarded as the most effective way to restore sinus rhythm in patients with chronic atrial fibrillation (AF), it remains unclear whether this procedure offers long-term clinical benefits in patients undergoing mechanical valve replacement. Methods and results Between 1999 and 2007, 402 patients with AF-associated mitral valve (MV) disease underwent MV replacement with a mechanical prosthesis. Of these patients, 159 underwent valve replacement plus the Maze procedure, whereas 243 received valve replacement alone. The composite end points of cardiac death and cardiac-related morbidities were compared in these two groups using the inverse-probability-of-treatment-weighted method. At a median follow-up time of 63.1 months (range 0.2–123.9 months), patients who had undergone the Maze procedure were at significantly lower risk of thromboembolic events (hazard ratio (HR)=0.26, 95% confidence interval (CI) 0.07 to 0.95; p=0.041) and were at comparable risk of death (HR=0.96, 95% CI 0.44 to 2.07; p=0.907) and cardiac death (HR=1.26, 95% CI 0.53 to 3.01; p=0.598) compared with patients who underwent MV replacement alone. The composite risk of death or major events was lower in the Maze procedure group (HR=0.64, 95% CI 0.38 to 1.08; p=0.093). Conclusions Compared with MV replacement alone, the addition of the Maze procedure was associated with a reduction in thromboembolic complications and better long-term event-free survival in patients with AF undergoing mechanical MV replacement. Prospective randomised data are necessary to confirm the findings of this study.

Outcomes After Unrestricted Use of Everolimus-Eluting and Sirolimus-Eluting Stents in Routine Clinical Practice A Multicenter, Prospective Cohort Study

Background— It remains unclear whether there are differences in the safety and efficacy outcomes between everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in contemporary practice. Methods and Results— We prospectively enrolled 6166 consecutive patients who received EES (3081 patients) and SES (3085 patients) between April 2008 and June 2010, using data from the Interventional Cardiology Research In-Cooperation Society-Drug-Eluting Stents Registry. The primary end point was a composite of death, nonfatal myocardial infarction (MI), or target-vessel revascularization (TVR). At 2 years of follow-up, the 2 study groups did not differ significantly in crude risk of the primary end point (12.1% for EES versus 12.4% for SES; HR, 0.97; 95% CI, 0.84–1.12, P=0.66). After adjustment for differences in baseline risk factors, the adjusted risk for the primary end point remained similar for the 2 stent types (HR, 0.96; 95% CI, 0.82–1.12, P=0.60). There were also no differences between the stent groups in the adjusted risks of the individual component of death (HR, 0.93; 95% CI, 0.67–1.30, P=0.68), MI (HR, 0.97; 95% CI, 0.79–1.18, P=0.74), and TVR (HR, 1.10; 95% CI, 0.82–1.49, P=0.51). The adjusted risk of stent thrombosis also was similar (HR, 1.16; 95% CI, 0.47–2.84, P=0.75). Conclusions— In contemporary practice of percutaneous coronary intervention procedures, the unrestricted use of EES and SES showed similar rates of safety and efficacy outcomes with regard to death, MI, sent thrombosis, and TVR. Future longer-term follow-up is needed to better define the relative benefits of these drug-eluting stents. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01070420.