Jae-Sik Jang

Randomized Comparison of Everolimus-Eluting Stent Versus Sirolimus-Eluting Stent Implantation for De Novo Coronary Artery Disease in Patients With Diabetes Mellitus (ESSENCE-DIABETES) Results From the ESSENCE-DIABETES Trial

Background— Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus. Methods and Results— This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23±0.27 versus 0.37±0.52 mm; difference, −0.13 mm; 95% confidence interval, −0.25 to −0.02; upper 1-sided 95% confidence interval, −0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11±0.26 versus 0.20±0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups. Conclusions— Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00997763.

Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel

Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥ 1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥ 1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.

Meta-analysis of three randomized trials and nine observational studies comparing drug-eluting stents versus coronary artery bypass grafting for unprotected left main coronary artery disease.

Clinical outcomes for unprotected left main coronary artery (ULMCA) disease between coronary artery bypass grafting (CABG) and drug-eluting stents (DESs) remain controversial. We aimed to compare the safety and efficacy of percutaneous coronary intervention (PCI) using DESs with CABG in patients with ULMCA disease. Databases were searched for clinical studies that reported outcomes after PCI with DESs and CABG for treatment of ULMCA disease. End points of this meta-analysis were mortality; composite of death, myocardial infarction (MI), or stroke; and target vessel revascularization at 1-year follow-up. Pooled effects were calculated using fixed-effects model (Mantel-Haenszel method) or random-effects models (Dersimonian-Laird method). Twelve clinical studies (3 randomized trials and 9 observational studies) with 5,079 patients were involved in this study. At 1-year follow-up, there were trends toward lower risk of death (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.45 to 1.02) and the composite end point of death, MI, or stroke (OR 0.70, 95% CI 0.49 to 1.00) in the DES group compared to the CABG group. However, target vessel revascularization was significantly higher in the DES group compared to the CABG group (OR 3.52, 95% CI 2.72 to 4.56). In conclusion, PCI with DESs is associated with favorable outcomes for mortality; composite end point of death, MI, or stroke; and a higher risk of target vessel revascularization compared to CABG in patients with ULMCA disease.

Preventive Strategies of Renal Insufficiency in Patients With Diabetes Undergoing Intervention or Arteriography (the PREVENT Trial)

Few studies have compared the ability of sodium bicarbonate plus N-acetylcysteine (NAC) and sodium chloride plus NAC to prevent contrast-induced nephropathy (CIN) in diabetic patients with impaired renal function undergoing coronary or endovascular angiography or intervention. Diabetic patients (n = 382) with renal disease (serum creatinine ≥1.1 mg/dl and estimated glomerular filtration rate <60 ml/min/1.73 m(2)) were randomly assigned to receive prophylactic sodium chloride (saline group, n = 189) or sodium bicarbonate (bicarbonate group, n = 193) before elective coronary or endovascular angiography or intervention. All patients received oral NAC 1,200 mg 2 times/day for 2 days. The primary end point was CIN, defined as an increase in serum creatinine >25% or an absolute increase in serum creatinine ≥0.5 mg/dl within 48 hours after contrast exposure. There were no significant between-group differences in baseline characteristics. The primary end point was met in 10 patients (5.3%) in the saline group and 17 (9.0%) in the bicarbonate group (p = 0.17), with 2 (1.1%) and 4 (2.1%), respectively, requiring hemodialysis (p = 0.69). Rates of death, myocardial infarction, and stroke did not differ significantly at 1 month and 6 months after contrast exposure. In conclusion, hydration with sodium bicarbonate is not superior to hydration with sodium chloride in preventing CIN in patients with diabetic nephropathy undergoing coronary or endovascular angiography or intervention.

Randomized Comparisons Between Different Stenting Approaches for Bifurcation Coronary Lesions With or Without Side Branch Stenosis

OBJECTIVES This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions. BACKGROUND The optimal bifurcation stenting technique needs to be evaluated. METHODS The trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non-left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis. RESULTS Between the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p=0.064), comprising 15.1% versus 3.7% for the main branch (p=0.004) and 2.8% versus 5.6% for the SB (p=0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p=0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p=0.44), comprising 5.2% versus 4.8% for the main branch (p=0.90) and 3.9% versus 8.3% for the SB (p=0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p=0.84). CONCLUSIONS Angiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non-left main bifurcation lesions once the procedure was performed successfully.

High post-clopidogrel platelet reactivity assessed by a point-of-care assay predicts long-term clinical outcomes in patients with ST-segment elevation myocardial infarction who underwent primary coronary stenting

BACKGROUND Recent studies have shown that post-clopidogrel high platelet reactivity (HPR), assessed by a point-of-care assay, is associated with a higher risk of adverse events after percutaneous coronary intervention (PCI). We assessed the clinical impact of HPR by the VerifyNow P2Y12 point-of-care assay in 181 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary PCI with drug-eluting stents (DES) at 3 hospitals. METHODS The primary endpoint of the study was the 12-month major adverse cardiovascular events (MACE), which comprised cardiovascular death, nonfatal MI and ischemic stroke. All patients received a single loading dose of 600 mg clopidogrel and 300 mg aspirin followed by a daily maintenance dose of 75 mg clopidogrel and 100mg aspirin. RESULTS A P2Y12 reaction unit (PRU) ≥ 282 (AUC 0.719, 95% CI 0.588-0.851, p=0.004, sensitivity 68.8%, specificity 73.8%) was the optimal cut-off value in predicting 12-month MACE by receiver operating characteristic curve analysis. Occurrence of MACE was significantly more frequent in patients with HPR (PRU ≥ 282) compared to patients without HPR (20.4% vs. 3.9%, HR 6.24, 95% CI 2.05-18.99, p=0.001). By multivariate analysis, HPR (HR 3.84, 95% CI 1.17-12.58, p=0.026) and elderly patients above 80 years of age (HR: 8.13, 95% CI 1.79-37.03, p=0.007) were found to be the significant predictors of 12-month MACE. The MACE-free survival rate was significantly lower in patients with HPR compared to patients without HPR (p<0.001). CONCLUSION HPR assessed by a point-of-care assay was able to predict 12-month MACE in patients with STEMI who underwent primary PCI with DES.

Meta-Analysis of Plaque Composition by Intravascular Ultrasound and Its Relation to Distal Embolization After Percutaneous Coronary Intervention

Controversies exist regarding the association between plaque composition and distal embolization phenomenon after percutaneous coronary intervention (PCI). We evaluated the effect of plaque characteristics on embolization after PCI by grayscale and virtual histology-intravascular ultrasound (IVUS). We searched PubMed, Ovid MEDLINE, and Cochrane databases for IVUS studies evaluating the coronary plaque characteristics in no reflow, distal embolization, and periprocedural myocardial infarction after PCI. Sixteen studies were included, totaling 1,697 patients who underwent PCI (292 patients with embolization and 1,405 patients without embolization). At the minimum lumen sites, the external elastic membrane (weighted mean difference 2.38 mm(2), 95% confidence interval [CI] 1.02 to 3.74) and the plaque and media cross-sectional areas (weighted mean difference 2.44 mm(2), 95% CI 1.44 to 3.45) were significantly greater in the embolization group than in the no embolization group. Pooled analysis showed that the absolute necrotic core volume (standardized mean difference 0.49, 95% CI 0.13 to 0.85), absolute (standardized mean difference 0.73, 95% CI 0.14 to 1.31) and relative (standardized mean difference 1.02, 95% CI 0.72 to 1.31) necrotic core areas at the minimum lumen sites were significantly greater in the embolization group than in the no embolization group, but the other plaque components were similar in the 2 groups. In conclusion, the necrotic core component derived from virtual histology-IVUS and the morphologic characteristics of plaque derived from grayscale IVUS are closely related to the distal embolization phenomenon after PCI.

Prognostic value of creatine kinase-myocardial band isoenzyme elevation following percutaneous coronary intervention: A meta-analysis

To assess whether different degrees of creatine kinase‐myocardial band isoenzyme (CK‐MB) elevation after percutaneous coronary intervention (PCI) affect the subsequent risk of death.

Preventive versus Culprit-Only Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction Patients with Multivessel Disease: A Meta-Analysis

BACKGROUND Although previous studies have suggested clinical benefits of complete revascularization in patients with multivessel coronary artery disease, it is still controversial whether preventive percutaneous coronary intervention (PCI) leads to better clinical outcomes in the clinical setting of ST-segment elevation myocardial infarction (STEMI). METHODS Relevant studies through September 2014 were searched and identified in the electronic databases.Primary endpoint was all-cause mortality at the longest follow-up. Secondary endpoints included myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). RESULTS From 836 initial citations, 7 randomized trials, and 23 observational studies with 44,256 patients (8,087 preventive and 36,169 culprit-only) were included in this study. Preventive PCI was associated with a significant reduction in repeat revascularization (odds ratios [OR]: 0.71; 95% CI: 0.51–0.99) with no differences in all-cause mortality (OR: 0.99; 95% CI: 0.76–1.29) or MI (OR: 1.08; 95% CI: 0.62–1.87) as compared with culprit-only PCI.Comparison of preventive PCI to the culprit-only PCI group revealed OR for MACE of 0.80 (95% CI: 0.57–1.12).Stratified analysis according to revascularization strategy demonstrated a significant survival benefit of culprit-only PCI over multivessel PCI during the index procedure and a significantly lower incidence of all-cause mortality with staged PCI as compared with culprit-only or multivessel PCI during the index procedure. CONCLUSIONS Preventive PCI strategy appears to be effective in reducing the risk of repeat revascularization without significant benefits for mortality or MI when compared with culprit-only revascularization in STEMI patients with multivessel disease.

Association of Smoking Status With Health-Related Outcomes After Percutaneous Coronary Intervention

Background—Patients who smoke at the time of percutaneous coronary intervention (PCI) would ideally have a strong incentive to quit, but most do not. We sought to compare the health status outcomes of those who did and did not quit smoking after PCI with those who were not smoking before PCI. Methods and Results—A cohort of 2765 PCI patients from 10 US centers were categorized into never, past (smoked in the past but had quit before PCI), quitters (smoked at time of PCI but then quit), and persistent smokers. Health status was measured with the disease-specific Seattle Angina Questionnaire and the EuroQol 5 dimensions, adjusted for baseline characteristics. In unadjusted analyses, persistent smokers had worse disease-specific and overall health status when compared with other groups. In fully adjusted analyses, persistent smokers showed significantly worse health-related quality of life when compared with never smokers. Importantly, of those who smoked at the time of PCI, quitters had significantly better adjusted Seattle Angina Questionnaire angina frequency scores (mean difference, 2.73; 95% confidence interval, 0.13–5.33) and trends toward higher disease specific (Seattle Angina Questionnaire quality of life mean difference, 1.97; 95% confidence interval, −1.24 to 5.18), and overall (EuroQol 5 dimension visual analog scale scores mean difference, 2.45; 95% confidence interval, −0.58 to 5.49) quality of life when compared with persistent smokers at 12 months. Conclusions—Smokers at the time of PCI have worse health status at 1 year than those who never smoked, whereas smokers who quit after PCI have less angina at 1 year than those who continue smoking.