Sang-Hoon Seol

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.

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.

Successful percutaneous coronary intervention for acute coronary syndrome in a patient with severe hemophilia a.

Patients with hemophilia generally have a reduced frequency of coronary artery disease compared to the general population. As advances in the management of hemophilia have increased their life expectancy, the prevalence of coronary artery disease also has increased. However, there are no standard treatment guidelines for coronary artery disease in patients with hemophilia, especially in the field of coronary intervention. We report the case of a patient with severe hemophilia A who presented with acute coronary syndrome and was successfully treated with percutaneous coronary intervention.

Fatal Subacute Stent Thrombosis Induced by Guidewire Fracture with Retained Filaments in the Coronary Artery

During percutaneous coronary intervention, guidewire fractures are very exceptionally encountered in medical practice, but can cause fatal complications such as intracoronary thrombus formation, embolization and perforation. Removal of the remnant segments of guidewire is important for the prognosis. There are several methods being recommended for the treatment of fractured guidewire remnants. However, the best treatment of remnant guidewire filament is still unclear. Herein, we present a case where we did not completely remove remnant guidewire filaments that caused fatal coronary thrombosis.

Detection of Clopidogrel Hyporesponsiveness Using a Point-of-Care Assay and the Impact of Additional Cilostazol Administration after Coronary Stent Implantation in Diabetic Patients

Background/Aims Impaired responsiveness to clopidogrel is common in patients with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the clinical application of a point-of-care assay to detect impaired responsiveness to clopidogrel after coronary stent implantation in patients with type 2 DM. Methods We measured P2Y12 reaction units (PRU) with the VerifyNow point-of-care assay in 544 consecutive patients undergoing dual or triple (i.e., dual plus cilostazol) anti-platelet therapy after coronary stent implantation. High platelet reactivity (HPR) was defined as a PRU value ≥ 240. Results The mean PRU values were 233.5 ± 83.2 and 190.3 ± 85.5 in patients undergoing dual or triple anti-platelet therapy, respectively (p < 0.001). Patients with DM manifested higher post treatment PRU values (238.3 ± 82.4 vs. 210.8 ± 86.8, p = 0.001) and a higher frequency of HPR (44.8% vs. 31.0%, p = 0.003) as compared to patients without DM. We also found that higher PRU values and a higher frequency of HPR were present in patients with DM who were undergoing both triple and dual anti-platelet therapy. However, the higher post-treatment PRU values observed in patients with DM decreased with triple anti-platelet therapy (219.4 ± 82.5 vs. 247.9 ± 81.1, p = 0.044). Conclusions A point-of-care assay can detect elevated platelet reactivity and impaired responsiveness to clopidogrel in patients with type 2 DM. The addition of cilostazol to dual anti-platelet therapy may decrease post-treatment PRU values in patients with type 2 DM.

Impact of Carvedilol Versus β1-Selective β Blockers (Bisoprolol, Metoprolol, and Nebivolol) in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Although β blocker (BB) has constituted one of the mainstays of evidence-based therapy for patients with acute myocardial infarction (AMI), the comparative efficacy of different BBs remains uncertain. We sought to determine the comparative effectiveness of nonselective BB carvedilol and the most frequently prescribed β1-selective BBs (bisoprolol, metoprolol, and nebivolol) in patients with AMI undergoing percutaneous coronary intervention (PCI). A total of 7,863 patients were selected from the prospective national AMI registry, and patients were divided into carvedilol group (n = 6,231) and β1-selective BB group (n = 1,632) at hospital discharge. The primary end point was all-cause death or MI during follow-up. During a mean follow-up of 243 ± 144 days, all-cause death or MI occurred in 94 patients (1.5%) in the carvedilol group versus 31 patients (1.9%) in the β1-selective BB group (adjusted hazard ratio 0.81, 95% confidence interval 0.54 to 1.22, p = 0.32). This result was consistent across various risk subgroups. The risks of all-cause death, cardiac death, and MI were also similar between the groups. After propensity-score matching, no difference was observed in the rate of all-cause death or MI (1.7% in the carvedilol vs 1.9% in the β1-selective BB group, adjusted hazard ratio 0.84, 95% confidence interval 0.49 to 1.46, p = 0.55). In conclusion, no differences in the risk of all-cause death or MI were observed between the carvedilol and β1-selective BB groups in contemporary practice of the treatment for AMI.

Two-year Clinical Outcomes of Patients with Long Segments Drug-Eluting Stents: Comparison of Sirolimus-Eluting Stent with Paclitaxel-Eluting Stent

Limited data are available on the long-term clinical efficacy of drug-eluting stent (DES) in diffuse long lesions. From May 2006 to May 2007, a total of 335 consecutive patients (374 lesions) were underwent percutaneous coronary intervention with implantation of long DES (≥ 30 mm) in real world practice. Eight-month angiographic outcomes and 2-yr clinical outcomes were compared between SES (n = 218) and PES (n = 117). Study endpoints were major adverse cardiac events including cardiac death, myocardial infarction, target-lesion revascularization, target-vessel revascularization and stent thrombosis. Baseline characteristics were similar in the two groups as were mean stent length (44.9 ± 15.2 mm in SES and 47.4 ± 15.9 in PES, P = 0.121). Late loss at 8 months follow-up was significantly lower in SES than in PES group (0.4 ± 0.6 mm in SES vs 0.7 ± 0.8 mm in PES, P = 0.007). Mean follow-up duration was 849 ± 256 days, and 2-yr cumulative major adverse cardiac events were significantly lower in the SES than in the PES group (5.5% in SES vs 15.4% in PES, P = 0.003). In conclusion, long-term DES use in diffuse long coronary lesions is associated with favorable results, with SES being more effective and safer than PES in this real-world clinical experience.

Therapeutic Strategy for In-Stent Restenosis Based on the Restenosis Pattern After Drug-Eluting Stent Implantation

Background and Objectives The aim of this study was to evaluate the outcomes of repeated percutaneous coronary intervention (PCI) based on the restenosis pattern in drug-eluting stent (DES) failure. Subjects and Methods From April 2003 to March 2006, all 67 patients (67 lesions) at our 3 centers who had DES in-stent restenosis (ISR) were enrolled. The patients were divided into 3 groups: group I had focal edge restenosis, group II had focal body restenosis, and group III had non-focal restenosis. All patients were treated with conventional PCI including plain old balloon angioplasty (POBA), cutting balloon angioplasty (CBA), and repeated DES implantation (Re-DES). Angiographic and clinical one year follow-up results for the 3 groups were evaluated. Results Sixteen patients were enrolled in group I, 36 in group II, and 15 in group III. Baseline clinical and angiographic characteristics and the proportion of patients in each group receiving each type of treatment strategy were not significantly different among the groups. Within each group, a comparison of angiographic and clinical outcomes for each therapeutic modality revealed that restenosis rates were not statistically different. Although rates of major adverse cardiac events (MACE) were not statistically different between groups I and II, in group III, MACE were 3-fold higher for the POBA (4/4, 100.0%) and CBA (4/4, 100.0%) subgroups than for Re-DES (1/3, 33.3%) (p=0.06), but the differences did not reach statistical significance. Conclusion The present study suggests that treatment of DES ISR should be individualized according to restenosis pattern: any PCI strategy appears appropriate for focal ISR patterns, while Re-DES might be a better choice for non-focal ISR patterns.

Multiple Sequential Complications After Sirolimus-Eluting Stent Implantation: Very Late Stent Thrombosis, Stent Fracture, In-Stent Restenosis, and Peri-Stent Aneurysm

A 55-year-old male patient presented with an acute myocardial infarction. A sirolimus-eluting stent (SES) was implanted in the proximal left anterior descending artery (LAD). Eight months later, there was a newly developed distal LAD lesion. An additional SES was implanted. Twenty-eight months after the index procedure of primary coronary intervention, the electrocardiogram showed ST elevation in the precordial leads and an emergency coronary angiogram showed diffuse stent thrombosis (ST) in the proximal LAD. Thirty-four months after the index procedure, coronary angiography showed a large peri-stent coronary aneurysm in the proximal LAD and focal in-stent restenosis (ISR) at the proximal edge of the distal LAD stent. On fluoroscopy, a fracture was noted in the middle part of the distal SES. A zotarolimus- eluting stent (ZES) was deployed and overlapped the restenosis and fracture sites. Forty months after the index procedure, there were no changes in the size of the aneurysm or in the other stent complications including the fracture and restenosis. At present, the patient has remained asymptomatic for eight months.