Jang Hyun Cho

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.

High incidence of mucosa-associated lymphoid tissue in primary thyroid lymphoma: a clinicopathologic study of 18 cases in the Korean population.

The present study aimed to evaluate the clinicopathologic features and treatment outcomes of patients with primary thyroid lymphoma (PTL). The patients included 14 women and four men with a median age of 50 years (range 31 – 82 years). Thirteen cases involved the thyroid alone (stage IE) and five cases involved the regional lymph nodes (stage IIE). Histopathologic studies revealed marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in 13 patients and diffuse large B-cell lymphoma (DLBCL) in three patients. The other two patients showed features of both MALT and DLBCL. Surgery and chemotherapy with or without radiotherapy were performed. All patients achieved complete remission. All 18 patients were alive with a median follow-up period of 55 months. The prognosis of patients with primary thyroid lymphoma appears to be favourable.

Prognostic value of left atrium remodeling after primary percutaneous coronary intervention in patients with ST elevation acute myocardial infarction.

The purpose of this study is to assess the relationship between left atrial (LA) size and outcome after acute myocardial infarction (AMI) in patients undergoing primary percutaneous coronary intervention (PCI) and to evaluate dynamic changes in LA size during long-term follow-up. Echocardiographic analyses were performed on 253 AMI patients (174 male and 79 female, 65.4 ± 13.7 yr) undergoing PCI. These subjects were studied at baseline and at 12 months. Clinical follow-up were done at 30.8 ± 7.5 months. We assessed LA volume index (LAVI) at AMI-onset and at 12-month. Change of LAVI was an independent predictor of new onset of atrial fibrillation or hospitalization for heart failure (P = 0.002). Subjects who survived the 12-month period displayed an increased LAVI mean of 1.86 ± 4.01 mL/m2 (from 26.1 ± 8.6 to 28.0 ± 10.1 mL/m2, P < 0.001). The subject group that displayed an increased LAVI correlated with a low left ventricular ejection fraction, large left ventricle systolic and diastolic dimensions and an enlarged LA size. In conclusion, change of LAVI is useful parameter to predict subsequent adverse cardiac event in AMI patients. Post-AMI echocardiographic evaluation of LAVI provides important prognostic information that is significantly greater than that obtained from clinical and laboratory parameters alone.

The Effects of Antiplatelet Agents in the Prevention of Ventricular Tachyarrhythmias during Acute Myocardial Ischemia in Rats.

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial

BACKGROUND Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. METHODS We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. FINDINGS Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57-1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41-2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68-3·35]; p=0·32). The rate of BARC type 2-5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45-1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. INTERPRETATION The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. FUNDING Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.

Extraskeletal Ewing's Sarcoma of the Head and Neck Presenting as Blindness

Extraskeletal Ewings sarcoma is rarely found in the head and neck regions. We report an unusual case of extraskeletal Ewings Sarcoma of the parapharynx region in a 49-year-old man who presented with blindness. MRI examination showed marked enhancement of tumor thrombosis involving the superior sagittal sinus, straight sinus, transverse sinus, sigmoid sinus, and internal jugular vein. The final diagnosis was extraskeletal Ewings sarcoma after biopsy of the internal jugular vein thrombosis by histopathological evaluation and immunohistochemical assay. In addition, the patient was diagnosed as having adenocarcinoma of the rectum by biopsy of the rectal mass. The patient was treated with systemic chemotherapy and showed improved response with durable remission. The patients visual acuity, however, did not improve.

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).

Clinical Outcomes in Patients with Intermediate Coronary Stenoses: MINIATURE Investigators (Korea MultIceNter TrIal on Long-Term Clinical Outcome According to the Plaque Burden and Treatment Strategy in Lesions with MinimUm Lumen ARea lEss Than 4 mm2 Using Intravascular Ultrasound)

Background and Objectives We evaluated the two-year clinical outcomes in patients with angiographically intermediate lesions according to the plaque burden and treatment strategy. Subjects and Methods We prospectively enrolled patients with angiographically intermediate lesions (diameter stenosis 30-70%) with an intravascular ultrasound (IVUS) minimum lumen area (MLA) <4 mm2 with 50-70% plaque burden of 16 Korean percutaneous coronary intervention centers. Patients were divided into medical therapy group (n=85) and zotarolimus-eluting stent group (ZES; Resolute) group (n=74). We evaluated the incidences of two-year major adverse cardiovascular events (MACE). Results A two-year clinical follow-up was completed in 143 patients and MACE occurred in 12 patients. There were no significant differences in the incidences of death (1.3% vs. 3.0%, p=0.471), target vessel-related non-fatal myocardial infarction (0.0% vs. 0.0%, p=1.000) and target vessel revascularizations (7.8% vs. 4.5%, p=0.425) between medical and ZES groups. Independent predictors of two-year MACE included acute myocardial infarction {odds ratio (OR)=2.87; 95% confidence interval (CI) 1.43-6.12, p=0.014}, diabetes mellitus (OR=2.46; 95% CI 1.24-5.56, p=0.028) and non-statin therapy (OR=2.32; 95% CI 1.18-5.24, p=0.034). Conclusion Medical therapy shows comparable results with ZES, and myocardial infarction, diabetes mellitus and non-statin therapy were associated with the occurrence of two-year MACE in patients with intermediate lesion with IVUS MLA <4 mm2 with 50-70% of plaque burden.

Comparison of 1-Year Outcomes of Triple (Aspirin + Clopidogrel + Cilostazol) Versus Dual Antiplatelet Therapy (Aspirin + Clopidogrel + Placebo) After Implantation of Second-Generation Drug-Eluting Stents into One or More Coronary Arteries: from the DECREASE-PCI Trial

This study sought to evaluate the impact of triple antiplatelet therapy on clinical outcomes in patients treated with second-generation drug-eluting stents (DES) for coronary artery disease. There are limited data regarding the impact of triple antiplatelet therapy in patients who underwent implantation of second-generation DES. We planned to randomly assign 2,110 patients treated with second-generation DES to triple (aspirin, clopidogrel, and cilostazol) and dual (aspirin, clopidogrel, and placebo) antiplatelet therapy groups. The primary end point was a composite of death, myocardial infarction, ischemic stroke, or target vessel revascularization (TVR) at 1 year since randomization. The study was stopped early owing to slow enrollment. In total, 404 patients (202 patients each in the triple and dual antiplatelet therapy groups) were finally enrolled. At 1 year, the primary end point had occurred in 3.6% and 9.4% of patients in the triple and dual antiplatelet therapy groups, respectively (hazard ratio [HR] of the triple group 0.396; 95% confidence interval [CI] 0.166 to 0.949; p = 0.038). There was no significant difference between the 2 groups regarding the occurrence of a composite of all-cause death, myocardial infarction, or ischemic stroke (HR 0.583; 95% CI 0.229 to 1.481; p = 0.256). However, the rates of TVR were significantly lower in the triple antiplatelet therapy group than in the dual antiplatelet therapy group (HR 0.118; 95% CI 0.015 to 0.930; p = 0.043). In conclusion, triple antiplatelet therapy with cilostazol after implantation of second-generation DES improved clinical outcomes, mainly by reducing TVR.

Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial

PURPOSE The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. METHODS Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). FINDINGS Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. IMPLICATIONS Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.