Jeong-Sook Seo

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.

Clinical characteristics of stent fracture after sirolimus-eluting stent implantation

BACKGROUND Despite several case reports of sirolimus-eluting stent (SES) fracture and concern regarding restenosis after successful SES implantation, the clinical characteristics of this problem are not well known. METHODS Clinical records and angiographic films of patients who received follow-up coronary angiography between February 2005 and October 2006 were retrospectively analyzed. RESULTS Among the 686 SES implanted in 479 patients, 27 fractures were found in 22 (3.2%) stents in 18 patients. All stent fractures occurred in long stented segments, i.e. >/=28 mm (range, 28 mm to 83 mm). Of the 22 fractured stents, sixteen (72.7%) were identified in the right coronary artery (RCA) and fifteen (68.2%) were found to have a fracture site within 10 mm from areas with increased rigidity due to metal overlap. The significant multivariate predictors of stent fracture were the stented length (Odds ratio 1.06; 95% confidence interval 1.04-1.09; p=0.001) and the RCA location (Odds ratio 4.44; 95% confidence interval 1.66-11.86; p=0.003). The binary restenosis rate was 22.7% and target lesion revascularization was performed in two (9.1%) fractured stents. CONCLUSIONS SES fracture was associated with a long stented segment, RCA location and metal overlap. Stent fracture may be another potential risk factor for restenosis after successful SES implantation.

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.

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.

Randomized comparison of new dual-antiplatelet therapy (aspirin, prasugrel) and triple-antiplatelet therapy (aspirin, clopidogrel, cilostazol) using P2Y12 point-of-care assay in patients with STEMI undergoing primary PCI

BACKGROUND Both new dual antiplatelet therapy (DAT; aspirin and prasugrel) and triple antiplatelet therapy (TAT; aspirin, clopidogrel and cilostazol) are more potent than classic DAT (aspirin and clopidogrel). We compared the antiplatelet efficacy between new DAT and TAT in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary coronary percutaneous coronary intervention (PCI). METHODS Forty patients who were eligible for primary PCI were prospectively randomized to DAT group (n=20) or TAT group (n=20) immediately after hospital arrival. The primary end point was P2Y12 reaction unit (PRU) determined with the VerifyNow P2Y12 point-of-care assay at the time of discharge. RESULTS PRU value at discharge was significantly lower in patients receiving DAT compared with that of TAT (84.5 ± 44.7 vs. 128.4 ± 74.9, p=0.032). Percent platelet inhibition was significantly higher for DAT compared with TAT at discharge (72.1 ± 12.2 vs. 57.5 ± 23.5, p=0.020). Inter-patient variability of PRU values at discharge was significantly smaller in patient taking DAT compared with TAT (p=0.026). CONCLUSION A new DAT is more potent antiplatelet therapy than TAT in patients with STEMI undergoing primary PCI.

Randomized Comparison of the Platelet Inhibitory Efficacy between Low Dose Prasugrel and Standard Dose Clopidogrel in Patients Who Underwent Percutaneous Coronary Intervention

Background and Objectives Increased bleeding rates with standard dose prasugrel have led to increased questions about the effectiveness and safety of the lower maintenance dose. We compared platelet inhibitory efficacy between low dose prasugrel and standard dose clopidogrel in patients on maintenance dose dual antiplatelet therapy. Subjects and Methods Forty-three patients who underwent percutaneous coronary intervention were randomized to receive 75 mg clopidogrel (n=23) or 5 mg prasugrel (n=20). Another 20 patients were allocated to 10 mg prasugrel as a reference comparison group. All patients (weight, ≥60 kg; age, <75 years) had been receiving 100 mg aspirin and 75 mg clopidogrel daily. The platelet function test was performed at baseline and 30 days after randomization. The primary endpoint was P2Y12 reaction unit (PRU) at 30 days between 5 mg prasugrel and 75 mg clopidogrel. Results No differences in baseline PRU values were observed among the three groups. The prasugrel (5 mg) group had a significantly lower PRU value compared with that of 75 mg clopidogrel (174.6±60.2 vs. 223.4±72.9, p=0.022) group at 30 days, whereas the 10 mg prasugrel group showed a lower PRU value (71.9±34.4) compared with that of the 5 mg prasugrel (p<0.001). The rate of high on-treatment platelet reactivity (PRU >235) was significant lower in the 5 mg prasugrel group than that in the 75 mg clopidogrel group (15.0% vs. 56.5%, p=0.010). Conclusion Prasugrel (5 mg) is more potent antiplatelet therapy than 75 mg clopidogrel in non-low body weight and non-elderly patients on a maintenance dose dual antiplatelet therapy.

Relationship between symptom-onset-to-balloon time and long-term mortality in patients with acute myocardial infarction treated with drug-eluting stents

BACKGROUND Time from hospital arrival to reperfusion in ST-segment elevation myocardial infarction (STEMI) has been predictive of in-hospital mortality. The purpose of this study was to evaluate the relationship between symptom-onset-to-balloon time and long-term mortality in patients with STEMI in the drug-eluting stent (DES) era. METHODS A series of 393 patients with STEMI treated with DES from 2005 to 2007 was stratified according to risk profile and preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade, and clinical, angiographic, and follow-up data were collected. RESULTS A total of 98 (24.9%) low-risk patients and 295 (75.1%) non-low-risk patients were identified. Three-year mortality rate was 3.1% for low-risk patients and 10.2% for non-low-risk patients (p=0.034), respectively; however it did not differ according to symptom-onset-to-balloon time in either low-risk (p=0.333) or non-low-risk patients (p=0.881). Similarly, symptom-onset-to-balloon time and mortality were not related to preprocedural TIMI flow (p=0.474 for TIMI 0-1; p=0.428 for TIMI 2-3). In multivariate analysis, final TIMI flow 0-2, systolic blood pressure <100 mmHg at admission, age ≥70 years, anterior infarction, C-reactive protein level, and peak creatine kinase myocardial band isoenzyme level were identified as independent predictors of 3-year mortality while symptom-onset-to-balloon time and preprocedural TIMI flow were not. CONCLUSIONS In STEMI patients treated with DES, symptom-onset-to-balloon time does not affect long-term outcomes even in individuals at non-low risk and with poor preprocedural TIMI flow grade.