Real-World Treatment Selection Factors and 7-Year Clinical Outcomes between Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Left Main Disease.

BACKGROUND: The decision-making factors and long-term clinical outcomes between PCI and CABG in left main (LM) disease are still not well defined in the real world. METHODS: We evaluated consecutive patients (n = 230) with LM disease either treated by PCI (n = 118) or CABG (n = 112). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, spontaneous myocardial infarction (MI), stroke, and target vessel revascularization (TVR) for 7 years. RESULTS: In the multivariate-adjusted analysis, the presence of intermediate EuroSCORE II and high SYNTAX scores predisposed to CABG. Isolated LM disease was associated with receiving PCI. The PCI group had a similar rate of MACE (HRadj 0.97, 95% CI [0.48-1.94], p = 0.92) and a lower tendency of hard MACE (HRadj 0.49, 95% CI [0.22-1.07], p = 0.07) compared to the CABG group, mainly due to the balance between a higher rate of TVR (HRadj 9.71, p = 0.02) and a lower rate of stroke (HRadj 0.22, p = 0.09) with the PCI group than in the CABG group. CONCLUSIONS: The decision making of treatment strategy was made based on clinical and angiographic factors. The selected patients who received PCI showed similar MACE and trend of a lower rate of composite hard endpoints despite multivariate adjustment.

Diagnostic performance of dual-energy computed tomography for detection of acute spinal fractures.

OBJECTIVE: To assess the diagnostic performance of dual-energy computed tomography (DECT) with the color-coded virtual non-calcium (VNC) technique for detecting acute fractures in patients after acute spine trauma, especially in an emergency clinical setting. MATERIALS AND METHODS: Our retrospective study included 31 patients presented to emergency department with suspected spine trauma. All patients underwent both DECT (80 kVp and 140 kVp) and MRI. Post-processing was performed using color-coded VNC technique. Two independent radiologists visually assessed color-coded VNC images in a random order, and one of the two readers re-assessed the images in 4 weeks after the initial assessment. They were allowed to read only color-coded VNC images and asked to determine the presence of acute fracture. To determine the standard reference point, the other two experienced radiologists made consensus readings on both grayscale CT and MRI. Sensitivity, specificity, PPV, NPV, and accuracy analyses were determined. Both intra- and inter-observer agreements were also calculated. RESULTS: A total of 217 vertebral bodies (65 thoracic and 152 lumbar vertebrae) were included in our study. Sensitivity was 83.3% and 76.7% for first and second readers, respectively. Specificity of 99.5% and 98.9%, PPV of 96.1% and 96.3%, NPV of 97.3% and 96.3%, and accuracy of 97.2% and 95.8%, respectively, were noted. Both intra-observer and inter-observer agreements indicated excellent agreement (κ = 0.86 and κ = 0.84, respectively). CONCLUSION: In spite of the relatively low sensitivity, DECT-based detection of acute spinal fractures showed good specificity, positive predictive value, negative predictive value, accuracy, and inter-/intra-observer agreements.

Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management: A Randomized Clinical Trial.

BACKGROUND: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. METHODS: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. RESULTS: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P=0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P=0.04) and fatal bleeding (1% [4/400] vs 0%, P=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. CONCLUSIONS: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02094963.

10-Year Outcomes of Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Artery Disease.

BACKGROUND: Comparative outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) disease were previously reported. However, data on very long-term (>10 years) outcomes are limited. OBJECTIVES: The authors compare 10-year outcomes after PCI and CABG for LMCA disease. METHODS: In this observational study of the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty versus Surgical Revascularization) registry, the authors evaluated 2,240 patients with unprotected LMCA disease who underwent PCI (n = 1,102) or underwent CABG (n = 1,138) between January 2000 and June 2006. Adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and target-vessel revascularization) were compared with the use of propensity scores and inverse-probability-weighting adjustment. The follow-up was extended to at least 10 years of all patients (median 12.0 years). RESULTS: In the overall cohort, there was no significant difference in adjusted risks of death and the composite outcome between the groups up to 10 years. The risk of target-vessel revascularization was significantly higher in the PCI group. In the cohort comparing drug-eluting stents and concurrent CABG, the 2 study groups did not differ significantly in the risks of death and the composite outcome at 5 years. However, after 5 years, drug-eluting stents were associated with higher risks of death (hazard ratio: 1.35; 95% confidence interval: 1.00 to 1.81) and the composite outcome (hazard ratio: 1.46; 95% confidence interval: 1.10 to 1.94) compared with CABG. CONCLUSIONS: In patients with significant LMCA disease, as compared with CABG, PCI showed similar rates of death and serious composite outcomes, but a higher rate of target-vessel revascularization at 10 years. However, CABG showed lower mortality and serious composite outcome rates compared with PCI with drug-eluting stents after 5 years. (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty versus Surgical Revascularization [MAIN-COMPARE]; NCT02791412).

A multicenter, randomized, and double-blind phase IV clinical trial to compare the efficacy and safety of fixed-dose combinations of amlodipine orotate/valsartan 5/160 mg versus valsartan/hydrochlorothiazide 160/12.5 mg in patients with essential hypertension uncontrolled by valsartan 160 mg monotherapy.

BACKGROUND: To determine whether the effectiveness and safety of fixed-dose combinations (FDCs) of amlodipine orotate/valsartan (AML/VAL) 5/160 mg are noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in hypertensive patients with inadequate response to valsartan 160 mg monotherapy. METHODS: This 8-week, active-controlled, parallel-group, fixed-dose, multicenter, double-blind randomized controlled, and noninferiority trial was conducted at 17 cardiovascular centers in the Republic of Korea. Eligible patients had mean sitting diastolic blood pressure (msDBP) ≥90 mm Hg despite monotherapy with valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n = 121; VAL/HCTZ group, n = 117), of whom 228 completed the study. RESULTS: At 8 weeks after randomization, msDBP was significantly decreased in both groups (-9.44 ±â€Š0.69 mm Hg in the AML/VAL group and -7.47 ±â€Š0.71 mm Hg in the VAL/HCTZ group, both P < .001 vs baseline). Between group difference was -1.96 ±â€Š1.00 mm Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target BP) from baseline to week 8 was significantly higher in the AML/VAL group than that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n = 82] in the VAL/HCTZ group, P = .016). At 8 weeks after randomization, mean uric acid level was significantly increased in the VAL/HCTZ group compared to that at baseline (0.64 ±â€Š0.08 mg/dL; P < .001). However, it was slightly decreased from baseline in the AML/VAL group (-0.12 ±â€Š0.08 mg/dL; P = .085). The intergroup difference was significant (P < .001). CONCLUSION: The effectiveness and safety AML/VAL 5/160 mg FDC are noninferior to those of VAL/HCTZ 160/12.5 mg FDC in patients with hypertension inadequately controlled by valsartan 160 mg monotherapy.

Improved early risk stratification of patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention using a combination of serum soluble ST2 and NT-proBNP.

BACKGROUND: Although soluble suppression of tumorigenicity 2 (sST2) in serum is known to be associated with ischemic heart disease and heart failure, data regarding its prognostic impact in ST-segment elevation myocardial infarction (STEMI) is limited. We evaluated the prognostic impacts of serum sST2 and other serum biomarkers in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS: Consecutive all 323 patients with STEMI that underwent primary PCI were enrolled. Blood tests and samples were obtained in an emergency room. The primary endpoint was 1-year major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization. RESULTS: Mean age was 59.1±13.1 years (men 84%). MACCE (20 cardiovascular deaths, 7 non-fatal MI, 4 non-fatal stroke, 7 ischemia-driven revascularizations) occurred in 38 patients (12%). After adjusting for confounding factors, Cox regression analysis revealed that high serum sST2 (>75.8 ng/mL mean value, adjusted hazard ratio 2.098, 95% CI 1.008-4.367, p = 0.048) and high serum NT-proBNP level (>400 pg/mL, adjusted hazard ratio 2.606, 95% CI 1.086-6.257, p = 0.032) at the time of presentation independently predicted MACCE within a year of primary PCI. Furthermore, when high serum sST2 level was combined with high serum NT-proBNP level, the hazard ratio of MACCE was highest (adjusted hazard ratio 7.93, 95% CI 2.97-20.38, p<0.001). CONCLUSION: Elevated serum levels of sST2 or NT-proBNP at the time of presentation were found to predict 1-year MACCE independently and elevated serum levels of sST2 plus NT-proBNP were associated with even poorer prognosis in patients with STEMI undergoing primary PCI.

Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial.

PURPOSE: Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. METHODS: This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. FINDINGS: After 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. IMPLICATIONS: Eight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.

Increasing injection frequency enhances the survival of injected bone marrow derived mesenchymal stem cells in a critical limb ischemia animal model.

Critical limb ischemia (CLI) is one of the most severe forms of peripheral artery diseases, but current treatment strategies do not guarantee complete recovery of vascular blood flow or reduce the risk of mortality. Recently, human bone marrow derived mesenchymal stem cells (MSCs) have been reported to have a paracrine influence on angiogenesis in several ischemic diseases. However, little evidence is available regarding optimal cell doses and injection frequencies. Thus, the authors undertook this study to investigate the effects of cell dose and injection frequency on cell survival and paracrine effects. MSCs were injected at 106 or 105 per injection (high and low doses) either once (single injection) or once in two consecutive weeks (double injection) into ischemic legs. Mice were sacrificed 4 weeks after first injection. Angiogenic effects were confirmed in vitro and in vivo, and M2 macrophage infiltration into ischemic tissues and rates of limb salvage were documented. MSCs were found to induce angiogenesis through a paracrine effect in vitro, and were found to survive in ischemic muscle for up to 4 weeks dependent on cell dose and injection frequency. In addition, double high dose and low dose of MSC injections increased vessel formation, and decreased fibrosis volumes and apoptotic cell numbers, whereas a single high dose did not. Our results showed MSCs protect against ischemic injury in a paracrine manner, and suggest that increasing injection frequency is more important than MSC dosage for the treatment CLI.

The role of insulin resistance and metabolic risk factors on culprit coronary plaque.

BACKGROUND: Detailed relationships between insulin resistance (IR) and vulnerable plaque are not clear, therefore, we sought the role of IR and metabolic risk factors on culprit coronary plaque. METHODS: Plaque components at a region of interest (ROI, 10mm) were analyzed by virtual histology intravascular ultrasound. IR was defined as quantitative insulin sensitivity check index (QUICKI) ≤ 0.33. Seven metabolic risk factors (5 risk factors for metabolic syndrome defined by ATP III, history of smoking, and hsCRP) for IR were determined. RESULTS: The data for 150 (males 104) patients were analyzed. Patients with IR (n = 69) had greater necrotic core (NC) at the ROI (21.2 ± 15.8mm(3) vs 15.7 ± 11.9 mm(3), p = 0.02) than in patients without IR (n = 81). The NC at the ROI was correlated with QUICKI (r = -0.16, p = 0.05), HbA1c (r = 0.24, p < 0.01), body mass index (r = 0.17, p = 0.04), presence of diabetes mellitus (r = 0.29, p < 0.001), hsCRP (r = 0.17, p = 0.04) and the numbers of risk factors for IR (r = 0.41, p < 0.001). The multivariate analysis revealed that the numbers of risk factors for IR was an independent factor for the NC at the ROI (beta coefficient = 0.44, p = 0.003), but QUICKI was not (beta coefficient = -0.01, p = 0.94). CONCLUSIONS: Instead of a single measurement of IR index or each metabolic risk factor, clustering of risk factors for IR plays an important role on plaque vulnerability. CONDENSED ABSTRACT: We investigated the role of insulin resistance (IR) on culprit coronary plaque. Patients with IR had a greater amount of necrotic core in culprit coronary lesions than in patients without IR. Rather than a single measurement of IR index or each metabolic risk factor, clustering of metabolic risk factors for IR plays an important role in plaque vulnerability in patients with coronary artery disease. Our study demonstrates the role of IR on culprit coronary plaque and highlights the importance of the clustering of metabolic risk factors for IR in vulnerable plaque pathogenesis.

Efficacy and tolerability of amlodipine camsylate/losartan 5/100-mg versus losartan/hydrochlorothiazide 100/12.5-mg fixed-dose combination in hypertensive patients nonresponsive to losartan 100-mg monotherapy.

PURPOSE: The aim of this study was to determine whether the efficacy and tolerability of amlodipine camsylate/losartan 5/100 mg/d (AML/LOS) are noninferior to those of losartan/hydrochlorothiazide 100/12.5 mg/d (LOS/HCTZ) fixed-dose combination in hypertensive patients unresponsive to losartan 100-mg/d monotherapy. METHODS: Male and female patients aged ≥ 18 years with hypertension despite 4-week, stable treatment with losartan 100-mg/d monotherapy were eligible for inclusion in this multicenter, randomized, double-blind study. Patients were randomly assigned to receive AML/LOS or LOS/HCTZ once daily for 8 weeks. The primary end point was the change from baseline to week 8 in sitting diastolic blood pressure (ΔsiDBP), and the secondary end points were the changes from baseline to 4 weeks in siDBP and sitting systolic BP (ΔsiSBP) and changes from baseline to 4 and 8 weeks in BP response rate. Tolerability was evaluated by physical examination, including vital sign measurement; laboratory analysis; and ECG. FINDINGS: Of 275 patients screened at 9 cardiovascular centers, 199 were enrolled (AML/LOS, n = 101; LOS/HCTZ, n = 98), and 183 completed the study. The demographic characteristics were similar between the 2 groups (mean age, 51.56 [9.97] years; men, 70.53%). At 8 weeks, the mean ΔsiDBP values were -11.54 (7.89) and -9.05 (6.57) mm Hg in the AML/LOS and LOS/HCTZ groups, respectively (both, P < 0.0001 vs baseline). The mean difference between the 2 groups was -2.57 mm Hg, a nonsignificant difference, meaning that AML/LOS was noninferior to LOS/HCTZ with regard to the primary end point. At 8 weeks, the mean uric acid level was changed significantly from baseline in the LOS/HCTZ group (+0.41 [0.80] mg/dL; P < 0.0001) but not in the AML/LOS group (-0.12 [0.82] mg/dL), representing a significant intergroup difference (P < 0.0001). Nineteen patients each in the AML/LOS (18.81%) and LOS/HCTZ (20.00%) groups experienced ≥ 1 adverse event, with 4 (3.96%) and 3 (3.16%) patients, respectively, experiencing 1 or more events considered by the investigators to have been treatment related. IMPLICATIONS: The efficacy and tolerability of AML/LOS 5/100 mg/d was found to have been noninferior to those of LOS/HCTZ 100/12.5 mg/d in these hypertensive patients nonresponsive to losartan 100-mg/d monotherapy.

Echocardiographic predictor of acute heart failure after spine surgery: a novel tissue Doppler index associated with a potentially fatal complication of the operation.

BACKGROUND CONTEXT: Acute heart failure (HF) is a potentially fatal complication after spine surgery. PURPOSE: We sought to identify clinical and echocardiographic predictors of postoperative HF in spine surgery patients. STUDY DESIGN: Retrospective observational study. PATIENT SAMPLE: A total of 305 patients (128 men; age, 65 ± 9 years) who underwent spine surgery were consecutively enrolled. A transthoracic echocardiography was performed to all patients before the index operation. Patients with a history of HF or with left ventricular (LV) systolic dysfunction (LV ejection fraction <50%) were excluded. OUTCOME MEASURES: Heart failure was defined according to the Framingham criteria. The presence of postoperative dyspneic symptom and the sign of bilateral ankle edema were recorded by the physicians. Chest X-ray was mandatory for all patients and interpreted by the two physicians, including at least one radiologist. METHODS: Clinical, operative, and echocardiographic parameters were compared between patents with and without acute HF during the postoperative period (duration, 11 ± 9 days). This study was supported by Boryung Pharmaceutical Company (Seoul, Republic of Korea; 13,440 USD). RESULTS: Postoperative HF occurred in 31 patients (10%). Compared with those without postoperative HF, these patients were older (73 ± 7 vs. 64 ± 9 years), had longer anesthesia time (7.4 ± 4.2 vs. 3.6 ± 2.1 hours), and were treated with a greater volume of fluid replacement during the operation (3.8 ± 0.7 vs. 1.3 ± 0.1 L) (p<.05 for all). On echocardiographic evaluation, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/E') was higher (11 vs. 8) and left atrial volume index was larger (20 ± 6 vs. 17 ± 6 mL/m(2)) in patients with HF than in the control group (p<.05 for all), whereas the differences in LV ejection fraction and LV size were not significant. In multivariate analysis, E/E' (odds ratio, 1.399; 95% confidence interval, 1.169-1.674; p<.0001), age, and quantity of replaced volume during surgery were independent predictors of postoperative HF. CONCLUSIONS: Acute HF after spine surgery was rather common even in previously healthy patients. E/E' reflecting LV filling pressure predicted postoperative HF in patients who underwent spine surgery.

Comparison of zotarolimus-eluting stents versus sirolimus-eluting stents versus paclitaxel-eluting stents for primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: results from the Korean Multicentre Endeavor (KOMER) acute myocardial infarction (AMI) trial.

AIMS: The aim of this study was to compare the efficacy and safety of zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: This study was a prospective, single-blind, multicentre, randomised trial. The primary endpoint was major adverse cardiac events (MACE) at 12 months post-procedure, defined as cardiac death, recurrent myocardial infarction (MI), or ischaemia-driven target lesion revascularisation (TLR). An angiographic substudy was performed at nine months among 348 patients. From October 2006 to April 2008, 611 patients with STEMI undergoing primary PCI were randomly assigned to treatment with ZES (n=205), SES (n=204), or PES (n=202). The cumulative incidence of MACE was 5.9% in the ZES group, 3.4% in the SES group and 5.7% in the PES group at 12-month follow-up (p=0.457). There was a trend towards a lower rate of ischaemia-driven TLR at 12- (p=0.092) and 18-month (p=0.080) follow-up in the SES group compared to the ZES and PES groups. No difference was observed in rates of cardiac death, recurrent MI and combined death and/or recurrent MI among three groups at 12- and 18-month follow-up. The rate of stent thrombosis was similar among the three groups (2.0% in each group, p=1.000). CONCLUSIONS: As compared with SES and PES, the use of ZES in patients with STEMI undergoing primary PCI, showed similar rates of MACE, cardiac death and recurrent MI at 12 and 18 months. There was a trend towards a higher rate of TLR with ZES or PES compared to SES.

Comparison of inflammatory markers for the prediction of neointimal hyperplasia after drug-eluting stent implantation.

BACKGROUND: We compared the relationship between inflammatory markers and neointimal hyperplasia (NIH) after drug-eluting stent (DES) implantation. METHODS: We implanted a single DES in 42 consecutive patients with stable angina. The plasma high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) levels were measured before, and 24 and 72 h after the procedure. Angiography and intravascular ultrasound were performed. RESULTS: No relationship was noted between the baseline hs-CRP level and NIH. A significant positive correlation was noted between NIH and the hs-CRP level obtained at 24 h (r=0.435, P=0.004), and 72 h (r=0.334, P=0.031) after the procedure. Interestingly, there was a positive correlation between the change (Δ) in the hs-CRP level and NIH at 24 h (r=0.414, P=0.006). The fourth quartile of the hs-CRP at 24 h after percutaneous coronary intervention (PCI) had significantly larger volume of NIH than the first quartile (20.1±25.1 vs. 2.7±6.4 mm, P<0.05). Moreover, NIH in the fourth quartile (20.9±26.4 mm) was higher than the first quartile (3.3±8.6 mm) of the Δ hs-CRP level at 24 h (P<0.05) after the procedure. Although the IL-6 level at the baseline and 72 h after the procedure were positively correlated with NIH (r=0.337, P=0.029 and r=0.435, P=0.004, respectively), the Δ IL-6 level at any stage was not correlated with NIH. Neither the MMP-9 level nor the Δ MMP-9 level at any stage was correlated with NIH. CONCLUSION: This prospective intravascular ultrasound study showed the inflammatory response after PCI, as measured by hs-CRP levels, but not the baseline hs-CRP level, predict NIH after DES implantation. Neither a change in the IL-6 nor MMP-9 levels at any stage after PCI reflected NIH.

High plasma interleukin-6 is associated with drug-eluting stent thrombosis: possible role of inflammatory cytokines in the development of stent thrombosis from the Korea Stent Thrombosis Registry.

BACKGROUND: Inflammation might contribute to the development of stent thrombosis (ST). The association between inflammatory cytokine concentrations and drug-eluting ST were evaluated. METHODS AND RESULTS: Among the 123 ST patients enrolled in the multicenter Korea Stent Thrombosis registry, plasma samples were available in 41 patients. The patients' clinical characteristics and plasma concentrations of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interleukin (IL)-6 were compared with 81 matched controls. Although the concentrations of 3 cytokines were higher in the ST group, they did not have significant differences. When divided into quartiles, the proportion of patients with the highest quartile of IL-6 was higher in the ST group than in the control group (44% vs. 16%, P = 0.001), and the highest IL-6 quartile was an independent predictor of ST for both early (adjusted hazard ratio [HR] 6.96; 95% confidence interval [CI] 1.75-27.66) and late ST (adjusted HR 4.71; 95%CI 1.06-20.92). In addition, the highest IL-6 quartile was an independent predictor of ST in those on clopidogrel (adjusted HR 7.70; 95%CI 1.97-30.13) but not in those who were off clopidogrel. CONCLUSIONS: Highest IL-6 quartile was associated with ST, especially in clopidogrel users regardless of the time of ST, suggesting the involvement of inflammatory cytokines in ST.

Long-term safety and efficacy of stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry.

OBJECTIVES: We performed the long-term follow-up of a large cohort of patients in a multicenter study receiving left main coronary artery (LMCA) revascularization. BACKGROUND: Limited information is available on long-term outcomes for patients with unprotected LMCA disease who underwent coronary stent procedure or coronary artery bypass grafting (CABG). METHODS: We evaluated 2,240 patients with unprotected LMCA disease who received coronary stents (n = 1,102; 318 with bare-metal stents and 784 with drug-eluting stents) or underwent CABG (n = 1,138) between 2000 and 2006 and for whom complete follow-up data were available for at least 3 to 9 years (median 5.2 years). The 5-year adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction [MI], or stroke; and target vessel revascularization [TVR]) were compared with the use of the inverse probability of treatment weighted method and propensity-score matching. RESULTS: After adjustment for differences in baseline risk factors with the inverse probability of treatment weighting, the 5-year risk of death (hazard ratio [HR]: 1.13; 95% confidence interval [CI]: 0.88 to 1.44, p = 0.35) and the combined risk of death, Q-wave MI, or stroke (HR: 1.07; 95% CI: 0.84 to 1.37, p = 0.59) were not significantly different for patients undergoing stenting versus CABG. The risk of TVR was significantly higher in the stenting group than in the CABG group (HR: 5.11; 95% CI: 3.52 to 7.42, p < 0.001). Similar results were obtained in comparisons of bare-metal stent with concurrent CABG and of drug-eluting stent with concurrent CABG. In further analysis with propensity-score matching, overall findings were consistent. CONCLUSIONS: During 5-year follow-up, stenting showed similar rates of mortality and of the composite of death, Q-wave MI, or stroke but higher rates of TVR as compared with CABG for patients with unprotected LMCA disease.

A multicenter, eight-week treatment, single-step titration, open-label study assessing the percentage of Korean dyslipidemic patients achieving LDL cholesterol target with atorvastatin starting doses of 10 mg, 20 mg and 40 mg.

BACKGROUND: This study was designed to evaluate the safety and efficacy of algorithm-based atorvastatin therapy initiated at different starting doses of 10, 20, and 40 mg in Korean dyslipidemic patients. METHODS: Five hundred seventy-four patients were screened, and 425 were enrolled (low risk, n = 29; intermediate risk, n = 45; high risk, n = 351). The starting dose depended on a patient's cardiovascular risk and LDL-cholesterol (LDL-C) levels. RESULTS: Of the patients, 253 (59.5%), 63 (14.8%) and 109 (25.6%) patients were assigned at baseline to 10 mg, 20 mg and 40 mg atorvastatin, respectively. 390 patients (91.8%) completed the study, and 35 discontinued prematurely. No patient in the low or intermediate risk groups was titrated to 80 mg at Week 4, whereas, 26 in the high risk group were. 81.9% of patients achieved their LDL-C target at Week 4, which was sustained through to Week 8 (86.0%). 89.1% of patients who were not titrated achieved their LDL-C target at Week 8, and 82.1% of patients who were titrated 1 step up achieved their LDL-C target at Week 8. Overall, about 40% reduction in LDL-C, non-HDL-C levels, and LDL-C/HDL-C ratio was observed during the follow-up. Triglyceride was reduced by approximately 10% by Week 8. HDL cholesterol was slightly increased over 8 weeks (2.6%). Atorvastatin was well tolerated at all dose levels. CONCLUSIONS: Patient-tailored statin therapy according to an individual's risk category and LDL-C levels was safe and effective with a quick achievement of LDL-C target in Korean dyslipidemic patients.

Stents versus coronary-artery bypass grafting for left main coronary artery disease.

BACKGROUND: Several studies have compared the treatment effects of coronary stenting and coronary-artery bypass grafting (CABG). However, there are limited data regarding the long-term outcomes of these two interventions for patients with unprotected left main coronary artery disease. METHODS: We evaluated 1102 patients with unprotected left main coronary artery disease who underwent stent implantation and 1138 patients who underwent CABG in Korea between January 2000 and June 2006. We compared adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and target-vessel revascularization) with the use of propensity-score matching in the overall cohort and in separate subgroups according to type of stent. RESULTS: In the overall matched cohort, there was no significant difference between the stenting and CABG groups in the risk of death (hazard ratio for the stenting group, 1.18; 95% confidence interval [CI], 0.77 to 1.80) or the risk of the composite outcome (hazard ratio for the stenting group, 1.10; 95% CI, 0.75 to 1.62). The rates of target-vessel revascularization were significantly higher in the group that received stents than in the group that underwent CABG (hazard ratio, 4.76; 95% CI, 2.80 to 8.11). Comparisons of the group that received bare-metal stents with the group that underwent CABG and of the group that received drug-eluting stents with the group that underwent CABG produced similar results, although there was a trend toward higher rates of death and the composite end point in the group that received drug-eluting stents. CONCLUSIONS: In a cohort of patients with unprotected left main coronary artery disease, we found no significant difference in rates of death or of the composite end point of death, Q-wave myocardial infarction, or stroke between patients receiving stents and those undergoing CABG. However, stenting, even with drug-eluting stents, was associated with higher rates of target-vessel revascularization than was CABG.

Comparison of efficacy and tolerability of amlodipine orotate versus amlodipine besylate in adult patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 8-week follow-up, noninferiority trial.

OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of amlodipine orotate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was designed as a noninferiority study. To be included in the study, previously untreated patients had to have a sitting diastolic blood pressure (SiDBP) of 90 to 109 mm Hg. Previously treated patients had to discontinue their current annhypertensive medications and have a baseline SiDBP between 90 and 109 mm Hg after a 2-week washout period. Patients who met the inclusion criteria were randomly assigned to receive 5 mg amlodipine orotate or 5 mg amlodipine besylate for 8 weeks. The medication dose was doubled (10 mg QD for either amlodipine orotate or amlodipine besylate) 4 weeks after enrollment if SiDBP was >or=90 mm Hg. The primary efficacy analysis was noninferiority of the difference in mean trough SiDBP changes from baseline for amlodipin eorotate as compared with amlodipine besylate after 8 weeks of treatment. For the secondary efficacy analysis, 2 other measures were analyzed after 8 weeks of treatment. The SiDBP response rate was defined as an SiDBP measurement<90 mm Hg at the last clinical follow-up visit or an absolute reduction of >or=10 mm Hg in SiDBP from baseline until the last clinical follow-up visit. In addition, noninferiority of the difference in mean trough sitting systolic blood pressure (SiSBP) changes from baseline was analyzed for amlodipine orotate as compared with amlodipine besylate. The drug compliance rate was estimated by pillcount. RESULTS: Eligible patients (n=109; 43 women and 66 men) were randomly assigned to receive amlodipine orotate (n=53) or amlodipine besylate (n=56). No significant differences were found in sex, age, weight, or current smoking between the groups (all, P=NS). The proportion of patients with previous antihypertensive medications was not different between the groups (47.2% [25/53] in the amlodipine orotate group and 50.0% [28/56] in the amlodipine besylate group; P=NS). No significant differences were found in baseline SiDBP (mean [SD], 100 [6] mm Hg [range, 90-109 mm Hg] in the amlodipine orotate group and 100 [6] mm Hg [range, 90-108 mm Hg] in the amlodipine besylate group; P=NS) or in baseline SiSBP (mean [SD], 149 [14] mm Hg [range, 125-179 mm Hg] in the amlodipine orotate group and 146 [10] mm Hg [range, 123-167 mm Hg] in the amlodipine besylate group; p=NS). The mean (SD) changes in SiDBP were -15.6 (6.3) mm Hg for the amlodipine orotate group and -14.5 (5.5) mm Hg for the amlodipine besylate groups was 1.1 (5.9) mm Hg (95% CI, -0.87 to infinity), and because the lower boundary of the 95% CI was greater than -5 mm Hg, amlodipine orotate was considered noninferior to amlodipine besylate. The response rate was 48 of 51 (94.1%) in the amlodipine orotate group compared with 50 (92.6%) of 54 in the amlodipine besylate group after 8 weeks of treatment (P=NS). The mean (SD) compliance rates were 97.6% (3.6%) in the amlodipine orotate group and 96.5% (4.3%) in the amlodipine besylate group (P=NS). The incidence of drug-related adverse events (AEs) was similar between the groups (1/53 [1.9%]) in the amlodipine orotate group vs 4/55 [7.3%] in the amlodipine besylate group; P=NS). The most common drug-related AE overall was peripheral edema (2/55 [3.6%]), and the most common of all the AEs was upper respiratory tract infection (4/55 [7.3%]) in the amlodipine besylate group. The most common drug-related AE was headache (1/53 [1.9%]) in the amlodipine orotate group and peripheral edema (2/55 [3.6%]) in the amlodipine besylate group. No severe AEs were found in either group. CONCLUSION: The reduction in SiDBP after 8 weeks of amlodipine orotate treatment was noninferior to that of amlodipine besylate in these Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction in SISBP after 8 weeks of amlodipine orotate treatment were not significantly different from those of amlodipine besylate treatment. Both agents were wel tolerated.