Woong Chol Kang

A New Strategy for Discontinuation of Dual Antiplatelet Therapy The RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation)

OBJECTIVES The goal of this study was to evaluate shorter duration (3 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation. BACKGROUND There have been few published reports of prospective randomized clinical studies comparing the safety and efficacy of shorter duration DAPT after DES implantation. METHODS We randomly assigned 2,117 patients with coronary artery stenosis into 2 groups according to DAPT duration and stent type: 3-month DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3-month DAPT, n=1,059) versus 12-month DAPT following the other DES implantation (standard therapy, n=1,058). We hypothesized that the E-ZES+3-month DAPT would be noninferior to the standard therapy for the primary composite endpoint (cardiovascular death, myocardial infarction, stent thrombosis, target\vessel revascularization, or bleeding) at 1 year. RESULTS The primary endpoint occurred in 40 (4.7%) patients assigned to E-ZES+3-month DAPT compared with 41 (4.7%) patients assigned to the standard therapy (difference: 0.0%; 95% confidence interval [CI]: -2.5 to 2.5; p=0.84; p<0.001 for noninferiority). The composite rates of any death, myocardial infarction, or stent thrombosis were 0.8% and 1.3%, respectively (difference: -0.5%; 95% CI: -1.5 to 0.5; p=0.48). The rates of stent thrombosis were 0.2% and 0.3%, respectively (difference: -0.1%; 95% CI: -0.5 to 0.3; p=0.65) without its further occurrence after cessation of clopidogrel in the E-ZES+3-month DAPT group. The rates of target vessel revascularization were 3.9% and 3.7%, respectively (difference: 0.2%; 95% CI: -2.3 to 2.6; p=0.70). CONCLUSIONS E-ZES+3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint. (REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following E-ZES implantation [RESET]; NCT01145079).

Clinical Impact of Intravascular Ultrasound–Guided Chronic Total Occlusion Intervention With Zotarolimus-Eluting Versus Biolimus-Eluting Stent Implantation Randomized Study

Background—There have been no randomized studies comparing intravascular ultrasound (IVUS)–guided versus conventional angiography–guided chronic total occlusion (CTO) intervention using new-generation drug-eluting stent Therefore, we conducted a prospective, randomized, multicenter trial designed to test the hypothesis that IVUS-guided CTO intervention is superior to angiography-guided intervention. Methods and Results—After successful guidewire crossing, 402 patients with CTOs were randomized to the IVUS-guided group (n=201) or the angiography-guided group (n=201) and secondarily randomized to Resolute zotarolimus-eluting stents or Nobori biolimus-eluting stents. The primary and secondary end points were cardiac death and a major adverse cardiac event defined as the composite of cardiac death, myocardial infarction, or target-vessel revascularization, respectively. After 12-month follow-up, the rate of cardiac death was not significantly different between the IVUS-guided group (0%) and the angiography-guided group (1.0%; P by log-rank test=0.16). However, major adverse cardiac event rates were significantly lower in the IVUS-guided group than that in the angiography-guided group (2.6% versus 7.1%; P=0.035; hazard ratio, 0.35; 95% confidence interval, 0.13–0.97). Occurrence of the composite of cardiac death or myocardial infarction was significantly lower in the IVUS-guided group (0%) than in the angiography-guided group (2.0%; P=0.045). The rates of target-vessel revascularization were not significantly different between the 2 groups. In the comparison between Resolute zotarolimus-eluting stent and Nobori biolimus-eluting stent, major adverse cardiac event rates were not significantly different (4.0% versus 5.7%; P=0.45). Conclusions—Although IVUS-guided CTO intervention did not significantly reduce cardiac mortality, this randomized study demonstrated that IVUS-guided CTO intervention might improve 12-month major adverse cardiac event rate after new-generation drug-eluting stent implantation when compared with conventional angiography-guided CTO intervention. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01563952.

Simvastatin combined with ramipril treatment in hypercholesterolemic patients

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Thus, we studied vascular responses to combination therapy in hypercholesterolemic patients. A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril (study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout. In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months. Simvastatin alone or combined with ramipril significantly changed lipoproteins, improved percent flow-mediated dilator response to hyperemia by 30±5% and 53±6%, respectively (P <0.001), and reduced plasma levels of malondialdehyde by 4±7% (P =0.026) and 25±4% (P <0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3±3% and 12±2%, respectively (P =0.049 and P <0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (P =0.036 and P <0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by −7±7% and 17±5%, respectively (P =0.828 and P <0.001, respectively). In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels, however, simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone (P <0.001 and P =0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both P <0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (P <0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients.

The Effect of Renin-Angiotensin-Aldosterone System Blockade on Contrast-Induced Acute Kidney Injury: A Propensity-Matched Study

BACKGROUND The role of the angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) in the pathophysiology of contrast-induced acute kidney injury (AKI) is controversial, and the available literature is contradictory. STUDY DESIGN A retrospective propensity score-matched study to analyze the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI. SETTING & PARTICIPANTS Using propensity score matching, 1,322 ACE-inhibitor/ARB recipients and nonrecipients were paired for analysis from 5,299 patients and fulfilled the inclusion criteria among 11,447 patients receiving coronary angiography (CAG) or percutaneous coronary intervention. PREDICTORS ACE-inhibitor/ARB use based on prescription and risk factors for contrast-induced AKI. OUTCOMES The incidence of contrast-induced AKI defined by AKI Network (AKIN) criteria: an absolute increase in serum creatinine levels ≥0.3 mg/dL or a relative increase ≥50% from baseline values within 48 hours after exposure to the contrast medium. MEASUREMENTS Baseline serum creatinine, hemoglobin, and albumin levels; volume of contrast agents; preprocedural medication; and post-CAG serum creatinine levels. RESULTS An ACE inhibitor/ARB was prescribed for 64.0% of patients receiving CAG. ACE-inhibitor/ARB users showed an increased incidence of contrast-induced AKI after propensity score matching (11.4% vs 6.3%; P < 0.001). In multivariable analysis, use of ACE inhibitors/ARBs remained an independent and significant predictor of contrast-induced AKI in an unmatched cohort (OR, 1.39; 95% CI, 1.10-1.76; P = 0.06). In the matched cohort, use of ACE inhibitors/ARBs also was associated with a higher adjusted OR of contrast-induced AKI (OR, 1.43; 95% CI, 1.06-1.94; P = 0.02). LIMITATIONS A retrospective study at a single center. CONCLUSIONS Use of ACE inhibitors/ARBs during CAG has a possible influence to increase the incidence of contrast-induced AKI. Further randomized clinical trials are warranted to confirm the effect of ACE-inhibitor/ARB therapy on the development of contrast-induced AKI.

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 and angiographic outcomes after implantation of sirolimus and paclitaxel-eluting stents

Objective: We compared the degree of systemic inflammation and its relation to the angiographic outcomes after drug-eluting stent (DES) implantations. Methods: We implanted a single DES in 79 stable angina patients (50 men; 60.4 (9.5) years of age; sirolimus-eluting stent (SES), n = 38; paclitaxel-eluting stent (PES), n = 41). The high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were determined before and at 24 hours, 72 hours, and 4 weeks after the percutaneous coronary intervention (PCI). An angiography and intravascular ultrasound (IVUS) were performed. Results: The hs-CRP and IL-6 levels at baseline did not differ between the two groups. The hs-CRP increased significantly from baseline at 24 hours and 72 hours after the PCI in both groups and there was a significant increase in the IL-6 level at 24 hours after the PCI in both groups. However, there was no significant difference between the two groups in any of the hs-CRP or IL-6 measurements. At follow-up, the late lumen loss was significantly higher in the PES group than in the SES group (0.57 (0.56) mm vs 0.28 (0.58) mm, respectively, p = 0.020). The neointimal hyperplasia (NIH) volume in the PES group was significantly higher than that in the SES group (23.1 (22.7) vs 3.8 (7.1) mm3, respectively, p = 0.000). The percentage luminal volume reduction was higher in the PES group than in the SES group (18.9 vs 3.9%, p = 0.002). The absolute values or change in the inflammatory markers did not correlate with the NIH or stent volume reduction. Conclusions: Our study showed that the benefits obtained from the SES, which reduce neointimal proliferation, are not probably mediated by the attenuation of the systemic inflammatory markers hs-CRP or IL-6.

Echocardiographic Assessments of Left Atrial Strain and Volume in Healthy Patients and Patients With Mitral Valvular Heart Disease by Tissue Doppler Imaging and 3-Dimensional Echocardiography

Background and Objectives The purpose of the current study was to assess left atrial (LA) physiology in relation to associations between LA volume change and regional tissue velocities and strains, and to extend this information to patients with mitral stenosis (MS) or mitral regurgitation (MR). Subjects and Methods Twenty-two healthy persons, 22 patients with moderate-to-severe MS, and 22 patients with moderate-to-severe MR were studied. Tissue velocities, strains, and time-volume curves of the LA were acquired using tissue Doppler imaging and 3-dimensional echocardiography. Results In healthy controls, the maximal LA volume was negatively correlated with the posterior wall longitudinal systolic strain (r=-0.45, p=0.03). The time-to-maximal LA volume was positively correlated with the time-to-posterior wall longitudinal peak strain (r=0.46, p=0.03) and the time-to-circumferential peak strain (r=0.59, p=0.004). The LA active emptying fraction (LAactEF) was positively correlated with the posterior wall longitudinal peak systolic and late diastolic tissue velocities. In patients with MS, the maximal LA volume was negatively correlated with the posterior wall radial peak systolic velocity and the longitudinal late diastolic velocity. In patients with MS, the LAactEF had an additional positive correlation with the anterior wall longitudinal and circumferential systolic velocities, whereas the patients with MR had an additional positive correlation between the LAactEF and the lateral wall longitudinal peak strain as compared with the healthy cantrols. Conclusion LA longitudinal and circumferential deformations are more related than radial deformation to determining LA volume and function. The LA of patients with MS revealed a greater pathologic physiology than those of patients with MR.

Diffuse multi-vessel coronary artery spasm: Incidence and clinical prognosis

BACKGROUND The incidence and clinical prognosis of diffuse and multivessel coronary spasm has not been reported. METHODS Patients with suspected vasospastic angina were prospectively enrolled. Left and right coronary angiogram was performed simultaneously after intravenous ergonovine injection. Spasm (>70% luminal narrowing) was sub-classified as diffuse (more than 20mm length), multivessel (more than 2 epicardial arteries). Clinical characteristics and prognosis were analyzed. RESULTS Patients (96 consecutive patients, 56 males, mean age 48 years) were divided into 3 groups: diffuse-multivessel spasm (group I, n=16, 16.7%), other types of spasm (group II, n=12, 12.5%) and control group (group III, n=68, 70.8%). The rates of males, alcohol drinkers and the mean triglyceride were higher, and high density lipoprotein was lower in group I compared to group III (all p<0.05), but similar to group II (all p=NS). Hard cardiovascular event rates did not differ among groups (one cardiac arrest but successful resuscitation in group I, one non-fatal myocardial infarction in group III) during follow up periods (mean, 41.2 ± 13.7 months). Chest pain free survivals during 1 year were lower in group I (66.7%) compared to group III (90%), but similar to group II (58.3%) (group I vs III, p<0.05 and group I vs II, p=NS). CONCLUSIONS Diffuse-multivessel spasm was not rare in patients with vasospastic angina and its prognosis is pretty good similar to patients with previously known variant angina with recommended medical treatment.

Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation.

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02–59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan–Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.

The Effects of Statin and Niacin on Plaque Stability, Plaque Regression, Inflammation and Oxidative Stress in Patients With Mild to Moderate Coronary Artery Stenosis

Background and Objectives The aim of this study was to compare the effects of a combination of niacin and simvastatin to simvastatin alone, on plaque regression and inflammatory makers. Subjects and Methods The study had a prospective, randomized design. Subjects were patients with intermediate coronary artery stenosis. A total of 28 patients received a combination of niacin 1,000 mg plus simvastatin 40 mg (N+S group, n=14); the other group received simvastatin 40 mg alone (S group, n=14). All patients had a baseline and a 9-month follow-up coronary angiogram and an intravascular ultrasound procedure. Parameters such as normalized total atheroma volume (nTAV) and percent atheroma volume (PAV) were analyzed before and after treatment as were inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), Matrix me-talloproteinase-9 (MMP-9) and soluble CD40 ligand (sCD40L). Results There was no difference in baseline characteristics between the two groups. The nTAV and PAV in the N+S group before and after treatment were not different than those in the S group. But the degree of changes (delta) in nTAV in the N+S group was greater than that in the S group (-21.6±10.68 vs. 5.25±42.19, respectively, p=0.024). Also, the change in PAV in the NS group was higher than that in the S group (-1.2±2.5 vs. -0.6±5, respectively, p=0.047. Changes in hs-CRP, MMP-9, and sCD40L in the NS group were significantly greater than those of the S group (-0.71±1.25, 73.5±64.9, -1,970±1,925 vs. -0.32±0.96, 62.5±30.6, -1,673±2,628, respectively). Conclusion The combination of niacin plus simvastatin decreases coronary plaque volume and attenuates the inflammatory response in patients with intermediate coronary artery stenosis.