Long-Term Comparison of Platinum Chromium Everolimus-Eluting Stent vs. Cobalt Chromium Zotarolimus-Eluting Stent　- 3-Year Outcomes From the HOST-ASSURE Randomized Clinical Trial.

BACKGROUND: There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677). CONCLUSIONS: PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

Impact of Heart Rate Reduction with Maximal Tolerable Dose of Bisoprolol on Left Ventricular Reverse Remodeling.

BACKGROUND: We aimed to evaluate effect of heart rate (HR) reduction on left ventricular reverse remodeling (LVRR) in Korean patients with heart failure with reduced ejection fraction (HFrEF). METHODS: Ambulatory patients with HFrEF, who had paired echocardiograms, N-terminal prohormone brain natriuretic peptide (NT-proBNP), and global assessment score (GAS) at baseline and 6-month (n = 157), were followed up on preset treatment schedule with bisoprolol. RESULTS: The LVRR occurred in 49 patients (32%) at 6-month. In multivariable analysis, independent predictors associated with LVRR were use of anti-aldosterone agent (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.80-9.71), young age (OR, 0.96; 95% CI, 0.92-0.99), high baseline HR (OR, 3.76; 95% CI, 1.40-10.10), and favorable baseline GAS (OR, 1.73; 95% CI, 1.06-2.81). Beneficial effect of bisoprolol, in terms of LVRR, NT-proBNP, and GAS, was remarkable in the high HR group (baseline HR ≥ 75 beats per minute [bpm]), which showed a large HR reduction. CONCLUSION: High baseline HR (≥ 75 bpm) showed an association with LVRR and improvement of NT-proBNP and GAS in patients with HFrEF. This seems to be due to a large HR reduction after treatments with bisoprolol. Trial registry at www.ClinicalTrials.gov, NCT00749034.

Usefulness of the parameters of quantitative myocardial perfusion contrast echocardiography in patients with chronic total occlusion and collateral flow.

BACKGROUND: Microvascular obstruction becomes more severe with longer duration of ischemia, such as chronic total occlusion (CTO) which used to have collateral flow. In this study, we explored the correlation between parameters measured using quantitative myocardial perfusion contrast echocardiography (MCE) and the angiographic collateral flow grades in patients with CTO. Furthermore, we investigated the usefulness of the parameters of quantitative MCE for the measurement of microvasculature changes after revascularization of CTO lesions. METHODS: Between January 2011 and January 2013, 44 patients who had undergone coronary angiography (CAG) due to chest pain and had confirmed CTO lesions were enrolled in this prospective observational study. All patients had baseline MCE within 24 hours after diagnostic CAG. Patients were then assigned to one of two groups: a medical therapy group (Group I, n = 20) or a reperfusion group with percutaneous coronary intervention (PCI) (Group II, n = 24). All patients had follow-up MCE 3 months later. RESULTS: Consistent with the CAG results in both groups, on baseline MCE, the myocardial blood flow (AI × ß) values were higher in Grade III collateral flow than in Grade I or II collateral flow (AI of collateral flow Grade I vs. Grade II vs. Grade III: 2.34 ± 2.65 vs. 2.52 ± 2.67 vs. 3.87 ± 4.57, P = 0.038). The plateau acoustic intensity (AI) and wall-motion score index (WMSI) were significantly improved at the 3-month follow-up after successful reperfusion with PCI (5.75 ± 3.52 before vs. 8.11 ± 6.02 after, P = 0.004) and (1.76 ± 0.83 before vs. 1.43 ± 0.64 after, P ≤ 0.001), respectively. However, the AI and WMSI values were not improved in the medical treatment group, (6.04 ± 4.64 before vs. 6.01 ± 5.52 after, P = 0.966) and (1.61 ± 0.82 before vs. 1.66 ± 0.67 after, P = 0.616), respectively. CONCLUSIONS: MCE is a useful tool for estimating microvascularity in patients with CTO lesions and correlates well with angiographic collateral flow.

Doppler-derived left ventricular negative dP/dt as a predictor of atrial fibrillation or ischemic stroke in patients with degenerative mitral regurgitation and normal ejection fraction.

INTRODUCTION: The aim of this study was to investigate the role of Doppler-derived left ventricular (LV) -dP/dt in predicting atrial fibrillation (AF) or ischemic stroke in patients with moderate to severe degenerative mitral regurgitation (MR). METHODS: Doppler-derived LV -dP/dt was determined from the continuous-wave Doppler spectrum of the MR jet (-dP/dt = 32/time between 3 and 1 m/sec) in 80 patients (mean age 59 ± 16 years, 41% men) with moderate to severe degenerative MR, normal LV ejection fraction (LVEF ≥ 60%), and sinus rhythm at diagnosis. Events were defined as new AF or ischemic stroke. RESULTS: During a mean follow-up of 18 ± 13 months, there were 9 events (6 new AF, 3 ischemic strokes). Univariate analysis showed that older age, decreased LV -dP/dt, increased LV mass index, and left atrial volume index (LAVI), shortened deceleration time (DT), reduced A' velocity, and elevated E/E' ratio, prolongation of pulmonary venous (PV) atrial reversal (AR) flow duration relative to mitral inflow A-wave duration (AR-Adur) were associated with events. In multivariate Cox regression analysis, Doppler-derived LV -dP/dt (for each 100 mmHg/sec increase, hazard ratio: 0.165, 95% confidence interval: 0.036-0.761, P = 0.021) and E/E' (hazard ratio: 0.820, 95% confidence interval: 0.682-0.987, P = 0.036) were significant independent predictors of AF or ischemic stroke. CONCLUSIONS: Doppler-derived LV -dP/dt is independently associated with the occurrence of AF or ischemic stroke in patients with moderate to severe degenerative MR and provides additional prognostic information.

Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. METHODS AND RESULTS: We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients. CONCLUSIONS: Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

Randomized trial comparing the efficacy between different types of paclitaxel-eluting stents: the comparison of efficacy between COroflex PLEASe ANd Taxus stent (ECO-PLEASANT) randomized controlled trial.

AIMS: Paclitaxel-eluting stents (PESs) have been shown to inhibit neointimal hyperplasia after percutaneous coronary intervention. Coroflex Please (B Braun, Melsungen, Germany) is a newly developed PES. We compared the clinical and angiographic efficacy of Coroflex Please with Taxus Liberte (Boston Scientific, Natick, MA) in a real-world practice. METHODS AND RESULTS: We performed a prospective, open-label, randomized, controlled study that enrolled 945 patients undergoing percutaneous coronary interventions in 18 centers in Korea. The primary end point was clinically driven target vessel revascularization at 9 months. The baseline characteristics were mostly similar and comparable between 2 groups. At 9 months, the incidence of clinically driven target vessel revascularization was 14.6% for Coroflex and 6.4% for Taxus, which was significantly different (hazard ratio 2.43, 95% CI 1.50-3.94, noninferiority P value = 1.000). This is well corroborated by the difference of in-stent late loss between 2 stents (0.71 ± 0.64 mm vs 0.52 ± 0.50 mm, P < .001) by 9-month follow-up angiography (n = 415 vs 215). Among secondary clinical end points, stent thrombosis (definite and probable) for 1 year was 2.2% in Coroflex and 1.3% in Taxus (P = .317). Also, myocardial infarction for 9 months was higher in Coroflex group than that in Taxus (4.9% vs 1.6%, P = .012), which was partly contributed by the higher incidence of periprocedural myocardial infarction in Coroflex arm (2.2% vs 0.3%, P = .028). CONCLUSIONS: Coroflex Please was inferior to Taxus Liberte with regard to clinical and angiographic efficacy.

Dyssynchrony contributes to false-positive myocardial perfusion SPECT results in patients with stable angina.

AIM: We designed this study to evaluate the possibility that dyssynchrony might lead to false-positive myocardial perfusion single photon emission computed tomography myocardial perfusion image (MPS) results in stable angina patients. METHODS AND RESULTS: This study included 61 patients with both clinically diagnosed stable angina and quantitative MPS results who underwent coronary angiography. The patients were divided into two groups: those who had positive MPS results and normal coronary angiography (Group I, n = 28, 64.05 ± 10.14 years, 11 males and 17 females) and those who had positive MPS results and significant coronary lesions as determined by coronary angiography (Group II, n = 33, 69.2 ± 10.4 years, 14 males and 19 females). The maximal difference in time-to-peak myocardial sustained systolic velocity among all 12 left ventricular (LV) segments (maximal difference in TS) was significantly delayed in Group I as compared with Group II (125.00 ± 46.10 vs. 87.33 ± 40.53 ms, P=0.001). The standard deviation of the time-to-peak myocardial sustained systolic velocity of all 12 LV segments (TS-SD) was also significantly different in the two groups (45.12 ± 19.25 vs. 30.10 ± 15.80 , P=0.002). CONCLUSION: Dyssynchrony may be a cause of false-positive quantitative MPS results, even if patients have narrow QRS complexes on ECG. Dyssynchrony index can increase the specificity of quantitative MPS in stable angina patients.

Coronary flow reserve is a comprehensive indicator of cardiovascular risk factors in subjects with chest pain and normal coronary angiogram.

BACKGROUND: The aim of the present study was to analyze the parameters related to baseline coronary flow velocity (CFV) and coronary flow reserve (CFR) using Doppler transthoracic echocardiography (TTE), and to assess their associations with components of the Framingham risk score (FRS), which estimates 10-year risk of coronary heart disease, in subjects with chest pain and a normal coronary angiogram. METHODS AND RESULTS: A total of 354 individuals (mean age: 55+/-11 years, M:F ratio =186:168) with angina or angina-like chest pain and a normal coronary arteriogram were enrolled. CFR, using TTE and adenosine or dipyridamole, was measured within 2 weeks after coronary angiogram. The clinical, electrocardiographic, echocardiographic and laboratory parameters related to baseline CVF and CFR were analyzed, and CFR was compared with FRS. There was an inverse correlation between baseline CFV and CFR (r=-0.374, P<0.001). On multivariate analysis the fulfilling of left ventricular hypertrophy criteria on electrocardiography was an independent predictor of baseline CFV for the upper 75% quartile (23.2> or =cm/s; odds ratio (OR) = 2.840, 95% confidence interval (CI) =1.155-6.983, P=0.023). On multivariate analysis hemoglobin A(1c) level was independently related to a CFR <2.0 (OR = 2.195, 95%CI = 0.920-1.005, P=0.013). CFR had an inverse correlation with FRS (r=-0.222, P<0.001). On multiple regression analysis among the components of the FRS system (FRSS), independent factors related to a CFR <2.0 included age (OR =1.033, 95%CI =1.000-1.067, P=0.041), high-density lipoprotein-cholesterol level (OR = 0.961, 95%CI = 0.933-0.991, P=0.012) and smoking status (OR = 2.461, 95%CI =1.078-5.618, P=0.033), respectively. CONCLUSIONS: CFR can be a comprehensive indicator of cardiovascular risk factors, including parameters of the FRSS, in subjects with chest pain and a normal coronary angiogram.

Change in ischemia-modified albumin and its clinical significance during exercise stress testing.

BACKGROUND: There is little data about the additive effects of ischemia-modified albumin (IMA) on the exercise stress test (EST) used for the screening of ischemic heart disease. The relationship between myocardial ischemic burden and the change in IMA (DeltaIMA) during EST was investigated. METHODS AND RESULTS: EST was performed using the Bruce protocol to evaluate chest pain or exertional dyspnea in 155 patients (men 89, 53+/-13 years). Blood samples for IMA were obtained before and immediately after EST. According to the EST results and the pattern of DeltaIMA, patients were categorized into 3 groups (none was classified as EST(-)/DeltaIMA(+)): (1) (EST(-); (2) EST(+)/DeltaIMA(-); and (3) EST(+)/DeltaIMA(+). After EST, 60 of 155 (38.7%) patients were EST(+) and 14/60 (23.3%) were EST(+)/DeltaIMA(+). Duke treadmill score was significantly lower in the EST(+)/DeltaIMA(+) group compared with the other groups (-9.0+/-7.9, -1.7+/-4.2, 6.7+/-4.4, respectively, P<0.001); 43/60 (72%) patients with EST(+) underwent coronary angiography and the proportion of patients with a large ischemic burden was higher in the EST(+)/DeltaIMA(+)group compared with the EST(+)/DeltaIMA(-) group (72.7% vs 15.6%, P=0.001). CONCLUSIONS: Increased IMA after EST suggests a large ischemic burden in coronary artery disease, so the DeltaIMA during EST may be useful for predicting the severity of myocardial ischemia.

Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy.

PURPOSE: The goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy. METHODS: This study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups. FINDINGS: Reductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non-HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074). IMPLICATIONS: Ezetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.

Lack of pathologic Q waves: a specific marker of viability in myocardial hibernation.

BACKGROUND: The present study evaluates the lack of Q waves on the electrocardiogram (ECG) in the prediction of myocardial viability compared with dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (Tl-201) scintigraphy. HYPOTHESIS: The lack of pathologic Q waves (NoQ) may be a readily available and specific marker for the presence of viability. METHODS: Sixty four patients with stable coronary artery disease (CAD) and ventricular dysfunction underwent rest ECG, DSE, and Tl-201 scintigraphy before revascularization, and a repeat rest 2-Dimensional (2-D) echocardiogram more than 3 mo later. RESULTS: Total viability at baseline (% of total segments) was higher in the NoQ group by Tl-201 scintigraphy (87 +/- 19% versus 70 +/- 20%, p = 0.008) and by DSE (81 +/- 20% versus 65 +/- 24%, p = 0.013). As expected, the sensitivity of NoQ waves was low in predicting recovery of function (23%), and inferior to Tl-201 (82%) and DSE (84%) (p<0.08). However, specificity of NoQ waves for predicting recovery of global function was high (72%); higher than Tl-201 (50%) and DSE (45%). Positive predictive values were comparable among all modalities. Results were similar if the data were analyzed regionally for viability. CONCLUSION: Lack of pathologic Q waves is a specific and readily available marker of myocardial viability in patients with chronic CAD, which should alert the clinician for myocardial hibernation.

Efficacy and Safety of Adding Omega-3 Fatty Acids in Statin-treated Patients with Residual Hypertriglyceridemia: ROMANTIC (Rosuvastatin-OMAcor iN residual hyperTrIglyCeridemia), a Randomized, Double-blind, and Placebo-controlled Trial.

PURPOSE: The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment. METHODS: This study was a multicenter, randomized, double-blind, placebo-controlled study. After a 4-week run-in period of rosuvastatin treatment, the patients who had residual hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus ω-3 fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group) with a 1:1 ratio and were prescribed each medication for 8 weeks. FINDINGS: A total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7% male). After 8 weeks of treatment, the percentage change from baseline in triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P < 0.001; non-HDL-C: -10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering effect of ω-3 fatty acids was greater when baseline TG or non-HDL-C levels were high and body mass index was low. The incidence of adverse events was not significantly different between the 2 groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.

Cardioprotective Effects of a Phlorotannin Extract Against Doxorubicin-Induced Cardiotoxicity in a Rat Model.

Long-term therapy with doxorubicin (DOX) is associated with high incidence of cumulative and irreversible dilated cardiomyopathy. The goal of this study was to evaluate the cardioprotective effects and safety of a phlorotannin extract from a brown algae Ecklonia cava (Seapolynol™, SPN) against DOX-induced cardiotoxicity in a rat model. A total of 42 rats were divided into six groups: control, low-dose SPN (LDS), high-dose SPN (HDS), DOX, DOX with low-dose SPN (DOX+LDS), and DOX with high-dose SPN (DOX+HDS). Echocardiography was performed at baseline and after 6 weeks. In left ventricular (LV) ejection fraction, DOX and DOX+LDS groups showed significant decreases (P < .001), while LDS, HDS, and DOX+HDS groups showed no significant change compared with control group. In LV mass index, DOX and DOX+LDS groups showed significant increases (P < .001 and P = .013), while LDS, HDS, and DOX+HDS groups showed no significant change compared with control group. In electron microscopy of the LV wall tissue, DOX+HDS group showed markedly less impaired myofibrils and mitochondria compared with both DOX and DOX+LDS groups. On the findings in echocardiography and electron microscopy, 6-week oral administration of SPN was safe and cardioprotective in a DOX-induced rat cardiotoxicity model in a dose-dependent manner.

Effects of metabolic syndrome on aortic pulse wave velocity.

BACKGROUND: The purpose of this study was to compare the value and evaluate the validity of non-invasive methods for the detection of vascular stiffness in never-treated individuals with metabolic syndrome (MetS). METHODS: A total of 59 subjects (mean age, 60 ± 12 years; male:female = 35:24) were enrolled in the study and were categorized into the positive MetS (MetS[+]: N = 32) and negative group (MetS[-]: N = 27), according to the parameters set by the National Cholesterol Education Program's Adult Treatment Panel III. Pulse wave velocity (PWV) of the aorta, arm, and leg, Framingham risk score (FRS), ankle-brachial index (ABI), and carotid intima-media thickness (IMT) for vascular aging were measured for the two groups. RESULTS: Aortic PWV (PWVaor) was significantly higher in MetS(+) than MetS(-) group (7.0 ± 1.4 m/s vs. 8.4 ± 1.6 m/s, p < 0.01), while ABI was significantly lower in MetS(+) than MetS(-) group (1.2 ± 0.1 vs. 1.1 ± 0.2, p = 0.03), respectively. FRS was significantly higher in MetS(+) than MetS(-) group (11 ± 5 vs. 14 ± 4, p = 0.05). The both mean IMT was higher in MetS(+) than MetS(-) group (right: 0.94 ± 0.20 mm vs. 0.81 ± 0.20 mm, p = 0.03; left: 0.93 ± 0.20 mm vs. 0.79 ± 0.20 mm, p = 0.03, respectively). For predicting the probability of the presence of MetS, PWVaor was an independent tool (p = 0.04; odds ratio, 1.88; 95% confidence interval, 1.03 to 3.42) and a cut-off value of PWVaor of 7.4 m/s showed a sensitivity of 66.7% and a specificity of 47.6%. CONCLUSIONS: We suggest that PWVaor, combined with traditional tools, can play an important role as a complementary or alternative tool for the detection of vascular stiffness in never-treated individuals with MetS.

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.

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.

Impact of the ß-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between ß adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study.

BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the ß-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 ± 14.3 to 70.0 ± 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 ± 2.62 mg vs. 3.96 ± 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring ß-blocker therapy according to genotype.

Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study.

PURPOSE: To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy. PATIENTS AND METHODS: Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2.5/40 mg (n=63), CKD-828 2.5/80 mg (n=63), or S-amlodipine 2.5 mg (n=61) for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings. RESULTS: After the 8-week treatment, changes in sitDBP/systolic BP (SBP) were -9.67±6.50/-12.89±11.78, -10.72±6.19/-13.79±9.41, and -4.93±7.26/-4.55±11.27 mmHg in the CKD-828 2.5/40 mg (P<0.0001/P<0.0001), CKD-828 2.5/80 mg (P<0.0001/P<0.0001), and S-amlodipine 2.5 mg (P<0.0001/P=0.0027) groups, respectively, which were all significant BP reductions. At Week 8, the CKD-828 2.5/40 mg (sitDBP/SBP: P=0.0002/P<0.0001) and CKD-828 2.5/80 mg (sitDBP/SBP: P=0.0001/P<0.0001) showed superior BP-lowering effects to S-amlodipine 2.5 mg (P<0.001). At Week 4, all groups showed significant antihypertensive effects but both CKD-828 combinations (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) exhibited superior BP-lowering effects to that of S-amlodipine 2.5 mg (sitDBP/SBP: P=0.0028/P=0.0001 and P<0.0001/P=0.0012, respectively). The adverse event incidence was significantly lower in the CKD-828 2.5/40 mg (9.52%, P=0.0086) than in the S-amlodipine 2.5 mg group (27.87%) and increasing the telmisartan dose induced no unexpected adverse events, suggesting the safety of CKD-828. CONCLUSION: CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

AIM: We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). METHOD: This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). RESULTS: Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. CONCLUSION: Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS.

The impaired flow reserve capacity of penetrating intramyocardial coronary arteries in apical hypertrophic cardiomyopathy.

BACKGROUND: Coronary flow reserve (CFR) capacity of penetrating intramyocardial coronary artery (PICA) in apical hypertrophic (AH) cardiomyopathy has not been studied yet. METHODS: We studied 65 patients with normal coronary angiogram results (mean age 56 +/- 10 years; 33 men, 32 women). Of these, 30 were normotensive without any left ventricular hypertrophy (control group), 24 had hypertension (HTN) without any left ventricular hypertrophy (HTN group), and 11 had AH cardiomyopathy (AH group). PICA-CFR and PICA-width ratio were calculated after the intravenous infusion of adenosine (140 microg/kg/min) just beneath the apical impulse window at a depth of 3 to 5 cm by using high-frequency transthoracic Doppler echocardiography. RESULTS: PICA-CFR was successfully measured in 59 (90.8%) of 65 patients. PICA-CFR was 1.65 +/- 0.49 in AH group, 2.50 +/- 0.77 in HTN group, and 2.42 +/- 0.73 in control group ( P < .005 vs HTN and control). PICA-width ratio was 1.45 +/- 0.42 in AH group, 2.14 +/- 0.72 in HTN group, and 1.81 +/- 0.55 in control group ( P = .025 vs HTN and control). PICA-CFR was closely related to width-ratio of PICA ( r = 0.448, P = .002). Conclusion PICA in AH has higher resting diastolic velocity, wider diameter, and impaired CFR compared with nonhypertrophied myocardium.