A Multi-Center, Prospective Observational Study to Investigate the Safety, Compliance, and Efficacy of Omethyl QTlet Soft Capsule.

Omega-3 fatty acids have been shown to be effective in lowering triglyceride (TG) levels; however, tolerability issues arise due to the large size of the pills. The purpose of this study was to examine the safety, compliance, and efficacy of Omethyl QTlet soft capsules (OQCs). This multi-center, prospective, observational study evaluated the safety, compliance, and efficacy of OQCs. Patients with hypertriglyceridemia with a history of omega-3 fatty acid intake were enrolled in this study and were prescribed OQCs (2 g−4 g/day) for eight weeks. All adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) were recorded for safety evaluation. Adherence to treatment was assessed using questionnaires, and efficacy was assessed by changes in lipid and lipoprotein levels after eight weeks from baseline. The convenience of taking medication was analyzed for 580 patients, and the efficacy test was performed for 563 patients. The AE and ADR rates were 8.2% and 5.7%, respectively. There were only two SAEs. Of the patients, 55.8% responded that the OQC improved medication convenience, and mean changes in TG, total cholesterol, LDL-C, and non-HDL-C from baseline to eight weeks were −37.88 mg/dL, −11.56 mg/dL, −5.55 mg/dL, and −10.87 mg/dL, respectively (p-values < 0.001). In patients who had previously taken omega-3 fatty acids, OQCs showed safety and efficacy in lowering TG, and it was confirmed that compliance with medicine also improved compared to omega-3 fatty acids.

Adherence to dabigatran and the influence of dabigatran-induced gastrointestinal discomfort in the real-world practice.

BACKGROUND: Dabigatran-induced gastrointestinal discomfort (DGID) is an important factor influencing the adherence to dabigatran. We investigated the incidence and risk factors of DGID and its impact on the adherence and persistence to dabigatran. METHODS: We prospectively enrolled the patients prescribed with dabigatran in 10 tertiary hospitals of the South Korea. The adherence was assessed using the percentage of the prescribed doses of the medication presumably taken by the patient (PDT by pill count). We evaluated the relationship between DGID and the baseline GI symptoms or the previous GI disease history using a questionnaire. RESULTS: A total of 474 patients (mean age 67.8 ± 9.3 years, male 68.6%, and mean CHA2DS2-VASc score 2.2 ± 1.2) were enrolled. The adherence assessed by the PDT was 93.5 ± 5.5% at 1-month and 96.4 ± 8.4% at 6-months among the persistent patients. During the 6-month follow-up, 82 (18.1%) patients discontinued dabigatran, and the most common reason for dabigatran discontinuation was DGID (49, 59.8%). Sixty-eight (14.3%) patients experienced DGID, and there was no difference in the clinical factors between those with or without DGID. Among the patients who experienced DGID, 42 discontinued dabigatran (61.8%). In a multivariate analysis, DGID was the only predictor of dabigatran discontinuation and a low adherence. CONCLUSION: Overall adherence of dabigatran was excellent, but those with DGID showed low adherence and persistence. Furthermore, it was challenging to predict DGID by clinical parameters. Therefore, it is recommended to follow the patients closely to check for DGID when prescribing dabigatran.

Changes in QRS Duration Are Associated with a Therapeutic Response to Sacubitril-valsartan in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Recent studies have demonstrated that angiotensin receptor neprilysin inhibitors (ARNIs) can reverse the cardiac remodeling effects that occur in heart failure with reduced ejection fraction (HFrEF). These studies have also suggested that ARNIs have favorable effects on ventricular dyssynchrony. We assessed the changes in QRS duration associated with ARNIs in patients with HFrEF. METHODS: We retrospectively investigated patients with HFrEF (defined by a left ventricular ejection fraction [LVEF] ≤ 35%) who were treated with ARNIs for at least six months. We divided the patients into QRS shortening and non-QRS shortening groups according to their electrocardiogram (ECG) findings. We also compared changes in echocardiographic parameters between the groups. RESULTS: A total of 68 patients with HFrEF were included (mean age: 62.5 years, 74.6% male). Twenty-one patients had significant ischemic heart disease (IHD). Thirty-five patients exhibited QRS-duration shortening on follow-up ECGs (mean change: -7.8 msec), and 33 patients showed no changes or increased QRS duration (mean change: 5.1 msec). The QRS shortening group exhibited significant improvement in LVEF (12.5 ± 15.3% vs. 1.7 ± 9.5%; p < 0.001) when compared with the non-QRS shortening group. The QRS shortening group also had significantly lower LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD) and LV mass index (LVMI) than did the non-QRS shortening group. The change in QRS duration was significantly correlated with the change in LVEF (r = -0.329, p = 0.011) and LVESD (r = 0.298, p = 0.022). CONCLUSIONS: Among patients with HFrEF treated with ARNIs, the QRS shortening group showed favorable LV systolic function recovery, and reversal of cardiac remodeling compared to those of the non-QRS shortening group. Change in the QRS duration, which reflects LV synchrony, may be associated with response to ARNIs in patients with HFrEF.

The matricellular protein CCN5 prevents adverse atrial structural and electrical remodelling.

Atrial structural remodelling including atrial hypertrophy and fibrosis is a key mediator of atrial fibrillation (AF). We previously demonstrated that the matricellular protein CCN5 elicits anti-fibrotic and anti-hypertrophic effects in left ventricles under pressure overload. We here determined the utility of CCN5 in ameliorating adverse atrial remodelling and arrhythmias in a murine model of angiotensin II (AngII) infusion. Advanced atrial structural remodelling was induced by AngII infusion in control mice and mice overexpressing CCN5 either through transgenesis (CCN5 Tg) or AAV9-mediated gene transfer (AAV9-CCN5). The mRNA levels of pro-fibrotic and pro-inflammatory genes were markedly up-regulated by AngII infusion, which was significantly normalized by CCN5 overexpression. In vitro studies in isolated atrial fibroblasts demonstrated a marked reduction in AngII-induced fibroblast trans-differentiation in CCN5-treated atria. Moreover, while AngII increased the expression of phosphorylated CaMKII and ryanodine receptor 2 levels in HL-1 cells, these molecular features of AF were prevented by CCN5. Electrophysiological studies in ex vivo perfused hearts revealed a blunted susceptibility of the AAV9-CCN5-treated hearts to rapid atrial pacing-induced arrhythmias and concomitant reversal in AngII-induced atrial action potential prolongation. These data demonstrate the utility of a gene transfer approach targeting CCN5 for reversal of adverse atrial structural and electrophysiological remodelling.

Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (-29.8% vs. 3.6%, P<0.001) and non-HDL-C (-10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Medical Resource Consumption and Quality of Life in Peripheral Arterial Disease in Korea: PAD Outcomes (PADO) Research.

BACKGROUND AND OBJECTIVES: We aimed to investigate the history of medical resource consumption and quality of life (QoL) in peripheral arterial disease (PAD) patients in Korea. METHODS: This was a prospective, multi-center (23 tertiary-hospitals, division of cardiology), non-interventional study. Adult patients (age ≥20 years) suffering from PAD for the last 12-month were enrolled in the study if they met with any of following; 1) ankle-brachial index (ABI) ≤0.9, 2) lower-extremity artery stenosis on computed tomography angiography ≥50%, or 3) peak-systolic-velocity-ratio (PSVR) on ultrasound ≥2.0. Medical chart review was used to assess patient characteristics/treatment patterns while the history of medical resource consumption and QoL data were collected using a patient survey. QoL was measured using EuroQoL-5-dimensions-3-level (EQ-5D-3L) score system, and the factors associated with QoL were analyzed using multiple linear regression analysis. RESULTS: This study included 1,260 patients (age: 69.8 years, male: 77.0%). The most prevalent comorbidities were hypertension (74.8%), hyperlipidemia (51.0%) and diabetes-mellitus (50.2%). The 94.1% of the patients took pharmacotherapy including aspirin (76.2%), clopidogrel (53.3%), and cilostazol (33.6%). The 12.6% of the patients were receiving smoking cessation education/pharmacotherapy. A considerable number of patients (500 patients, 40.0%) had visit history to another hospital before diagnosis/treatment at the current hospital, with visits to orthopedic units (50.4%) being the most common. At the time, 29% (or higher) of the patients were already experiencing symptoms of critical limb ischemia. Baseline EQ-5D index and EQ VAS were 0.64±0.24 and 67.49±18.29. Factors significantly associated with QoL were pharmacotherapy (B=0.05053; p=0.044) compared to no pharmacotherapy, and Fontaine stage improvement/maintain stage I (B=0.04448; p<0.001) compared to deterioration/maintain stage II-IV. CONCLUSIONS: Increase in disease awareness for earlier diagnosis and provision of adequate pharmacotherapy is essential to reduce disease burden and improve QoL of Korean PAD patients.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis - coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial.

INTRODUCTION: We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies. METHODS AND ANALYSIS: The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2×2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding. ETHIC APPROVAL AND DISSEMINATION: All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers. TRIAL REGISTRATION NUMBER: NCT02601157; Pre-results.

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.

The Combined Impact of Neutrophil-to-Lymphocyte Ratio and Type 2 Diabetic Mellitus on Significant Coronary Artery Disease and Carotid Artery Atherosclerosis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a new important inflammatory marker for predicting cardiovascular events. This study aimed to evaluate the combined impact of NLR and type 2 diabetes mellitus (T2DM) on significant coronary artery disease (CAD) and carotid artery atherosclerosis. METHODS: This study includes a total of 828 patients evaluated by coronary angiography and carotid ultrasonography. Significant CAD was defined as at least one vessel with stenosis greater than 50%. We employed logistic regression models to investigate the association of NLR and T2DM with significant CAD. The goodness-of-fit and discriminability of the models were assessed by the loglikelihood ratio test and C-index, respectively. Also, we investigated the clinical relevance of the categorized NLR that classifies patients into three risk groups (low, intermediate, high). RESULTS: According to logistic regression analysis, both NLR {adjusted odds ratio (OR) 1.31, p < 0.001} and T2DM (adjusted OR 2.46, p = 0.006) were independent risk factors of significant CAD. The addition of NLR and T2DM into a logistic regression model including conventional cardiovascular risk factors significantly improved the goodness-of-fit (p < 0.001) and the discriminability of the model (p = 0.004). Also, T2DM patients assigned into the high risk group (NLR > 2) showed the greater prevalence of significant CAD and carotid artery atherosclerosis compared with patients without T2DM or type 2 diabetic patients assigned into the low risk group (NLR ≤ 1). CONCLUSION: Our results suggest that type 2 diabetic patients with high inflammatory state would be more vulnerable to significant CAD and carotid artery atherosclerosis.

A Randomized, Double-blind, Candesartan-controlled, Parallel Group Comparison Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan in Patients with Mild to Moderate Essential Hypertension.

PURPOSE: A new antihypertensive drug that selectively blocks angiotensin II receptor type 1, fimasartan, has a potent and rapidly acting antihypertensive effect. We investigated the antihypertensive effects of fimasartan 60 and 120 mg and its safety in comparison to 8 mg of candesartan. METHODS: This clinical trial is a multicenter, randomized, double-blind, active comparator, and parallel group study. Three hundred sixty-two individuals were screened, and 290 patients aged 19 to 75 years with mild to moderate hypertension (diastolic blood pressure [DBP], 90-110 mm Hg) were randomly assigned to 60 to 120 mg/d of fimasartan or 8 mg/d of candesartan after a 2-week placebo run-in period. Treatments were administered for 12 weeks without dosage adjustment. The primary end point was the differences in DBP changes at week 12. FINDINGS: After 12 weeks of treatment, DBP and systolic blood pressure (SBP) decreased significantly in all 3 groups. The decrease in DBP at week 12 was larger but not statistically significant in the fimasartan 60 mg compared with the candesartan 8 mg group with a mean (SD) difference of 1.72 (8.32) mm Hg (95% CI, -0.71 to 4.15 mm Hg; P = 0.17). The lower margin of the CI (-0.71 mm Hg) exceeded the noninferiority margin (-3.5 mm Hg). The DBP-lowering effect of fimasartan 120 mg was also nonsignificantly larger than candesartan 8 mg (difference, 1.58 [8.27] mm Hg; P = 0.20). The decrease in SBP was also nonsignificantly larger in the fimasartan 60 mg group compared with the candesartan 8 mg group (difference, 3.50 [12.63] mm Hg; P = .06). The SBP-lowering effect of fimasartan 120 mg was statistically larger than candesartan 8 mg (difference, 4.98 [13.99] mm Hg; P = .02). Response rate (DBP <90 mm Hg or DBP lowering >10 mm Hg at week 12) was also nonsignificantly greater in both fimasartan groups (Fimasartan 60 mg, 81%; fimasartan 120 mg, 72%; candesartan 8 mg, 71%). The safety profile of the fimasartan 60 mg and 120 mg was similar to candesartan 8 mg, with a slightly higher, but statistically not significant, incidence of hepatic enzyme elevation in fimasartan 120 mg. IMPLICATIONS: The antihypertensive effect of fimasartan, a newly available angiotensin II receptor type 1 blocker, is comparable, although not superior, to candesartan with a good safety profile. ClinicalTrials.gov identifier: NCT01135212.

Beneficial Effect on Surrogate Markers of Heart Failure with Bisoprolol Up-Titration to Recommended Targets in Korean Patients with Heart Failure and Left Ventricular Systolic Dysfunction.

INTRODUCTION: The objective of this study was to establish the benefit of bisoprolol up-titration toward recommended dosage targets, versus lower-dose maintenance, in heart failure (HF) patients with systolic dysfunction. METHODS: Korean HF patients received bisoprolol 1.25 mg/day, incrementally up-titrated toward 10 mg/day in the absence of contraindications. After 26 weeks' treatment, patients were grouped as low-dose (<3.75 mg/day) or high-dose (≥3.75 mg/day). Primary endpoint was change in serum N-terminal probrain natriuretic peptide (NT-proBNP). Other markers of HF were also evaluated. RESULTS: 159 of 180 enrolled patients were evaluable. After 16 weeks' follow-up, there were 52 and 107 patients in the low- and high-dose groups respectively. Mean bisoprolol dosage was 5.4 mg/day; 24% of patients achieved target (10 mg/day). Mean logNT-proBNP significantly decreased in both groups, with no significant difference in the magnitude of change between groups. Mean heart rate (HR) and blood pressure decreased significantly in both groups, but only HR showed a significantly greater change in high-dose versus low-dose patients. In both groups, mean left ventricular (LV) end-systolic and end-diastolic dimensions were significantly decreased and mean LV ejection fraction was significantly improved. Mean 6-min walk test distances improved in both groups (significant in low-dose patients only). Functional class improvement was observed in both low- and high-dose patients. No patients were rehospitalized due to aggravated HF. CONCLUSIONS: In HF patients with systolic dysfunction, any bisoprolol dose is beneficial, but an attempt to up-titrate toward guideline-recommended dosages offers additional benefit in terms of restoration of LV systolic function and remodeling.

Association between the N-terminal plasma brain natriuretic peptide levels or elevated left ventricular filling pressure and thromboembolic risk in patients with non-valvular atrial fibrillation.

BACKGROUND: We aimed to investigate the role of brain natriuretic peptide (BNP) levels and left ventricular (LV) filling pressures in thromboembolic risk in patients with non-valvular atrial fibrillation (AF). METHODS: Among 327 patients with non-valvular AF, the ratio of peak early filling velocity to mitral annulus velocity (E/Ea) and N-terminal proBNP (NT-proBNP) was compared according to the presence of left atrial appendage (LAA) dysfunction [presence of spontaneous echo contrast (SEC)≥grade 3 and/or reduced LAA emptying flow velocity <20cm/s]. RESULTS: Compared to patients without LAA dysfunction, patients with LAA dysfunction presented with significantly higher CHADS2 scores (1.24±1.14 vs. 1.68±1.31, p=0.005), high-sensitivity C-reactive protein (0.36±1.18mg/dl vs. 0.66±1.32mg/dl, p=0.043), and NT-proBNP (765.3±2534.8pg/ml vs. 2266.9±6117.4pg/ml, p=0.002). Furthermore, patients with LAA dysfunction showed significantly higher left atrial volume index (LAVI, 25.1±10.9 vs. 43.1±22.1, p<0.001) and E/Ea (10.8±7.27 vs. 7.97±2.50mg/dl, p<0.001). Plasma logNT-proBNP levels were significantly correlated with the presence of SEC (r=0.276, p<0.001), LAA emptying flow velocity (r=-0.492, p<0.001), LAVI (r=0.405, p<0.001), and E/Ea (r=0.353, p<0.001). Binary logistic regression analysis showed that high NT-proBNP level >249.7pg/ml (odds ratio, OR 6.79, 95% confidence interval, CI 3.16-15.55, p<0.001) and E/Ea >10 (OR 4.41, 95% CI 2.39-8.15, p<0.001) were independent predictors of LAA dysfunction after adjustment of known thromboembolic risk factors. CONCLUSION: Elevated plasma NT-proBNP concentrations and LV filling pressures represented by LAA dysfunction may be reliable surrogate markers for predicting thromboembolic risk in patients with AF.

Epicardial Fat Thickness and Neutrophil to Lymphocyte Ratio are Increased in Non-Dipper Hypertensive Patients.

BACKGROUND: In this study, we aimed to investigate the relationship between echocardiographic epicardial fat thickness (EFT), neutrophil to lymphocyte ratio (NLR; an important inflammatory marker), and diurnal blood pressure (BP) changes in patients with recently diagnosed essential hypertension. METHODS: A total of 647 patients underwent echocardiography and 24 hours of ambulatory BP monitoring. EFT was measured by echocardiography, while NLR was measured by dividing the neutrophil count by the lymphocyte count. Patients were categorized into three groups according to BP pattern: the normotensive group, the dipper group, and the non-dipper group. RESULTS: The mean EFT was highest in the non-dipper group (non-dipper group, 7.3 ± 3.0 mm; dipper group, 6.1 ± 2.0 mm; control group, 5.6 ± 2.0 mm; p < 0.001). NLR was also highest in the non-dipper group (non-dipper, 2.75 ± 2.81; dipper, 2.01 ± 1.32; control, 1.92 ± 1.11; p < 0.001). EFT was significantly correlated with age (r = 0.160, p < 0.001) and NLR (r = 0.353, p < 0.001). Furthermore, an EFT ≥ 7.0 mm was associated with the non-dipper BP pattern with 51.3% sensitivity and 71.6% specificity [95% confidence interval (CI) = 0.56-0.65, p < 0.001]. In a multivariate analysis, EFT [adjusted odds ratio (OR) = 3.99, 95% CI = 1.22-13.10, p = 0.022] and NLR (OR = 1.34, 95% CI = 1.05-1.71, p = 0.018) were independent parameters that distinguished a non-dipper pattern after adjustment for cardiovascular risk factors. CONCLUSION: EFT and NLR are independently associated with impaired diurnal BP profiles in hypertensive individuals. EFT (as measured by echocardiography) and NLR appear to be helpful in stratifying cardiometabolic risk.

Comparative effect on platelet function of a fixed-dose aspirin and clopidogrel combination versus separate formulations in patients with coronary artery disease: A phase IV, multicenter, prospective, 4-week non-inferiority trial.

BACKGROUND/OBJECTIVES: The effect of aspirin and clopidogrel in a fixed-dose combination (FDC) on platelet function was compared with separate formulations in patients that had undergone percutaneous coronary intervention (PCI) with drug-eluting stent (DES). METHODS: This was a phase IV, prospective, multicenter, single-arm, non-inferiority study. Patients that had taken aspirin 100 mg and clopidogrel 75 mg once daily as separate formulations for >6 months after PCI with DES were enrolled, and then switched to an aspirin/clopidogrel FDC once-daily for 4 weeks. Platelet reactivity was determined using the VerifyNow® P2Y12 assay at baseline (immediately prior to switching) and 4 weeks later. RESULTS: A total of 648 patients (the full-analysis population; age, 63.6±9.0 years; male, 76.5%) finished the study, and 565 (the per-protocol population) completed without protocol violations. In the per-protocol population, the % inhibitions of P2Y12 and ARU were not significantly different between baseline and after 4 weeks of FDC treatment (29.2±20.0% to 29.0±19.9%, P=0.708; 445.1±69.2 to 446.2±63.0, P=0.799, respectively) and the difference in P2Y12 inhibition observed did not exceed the predetermined limit of non-inferiority (95% CI, -0.9 to 1.3). In the full-analysis population, the % inhibitions of P2Y12, PRU, and ARU were not significantly changed after 4 weeks of FDC treatment. CONCLUSIONS: This study demonstrates that the efficacy of platelet inhibition by an aspirin/clopidogrel FDC was not inferior to that of separate aspirin and clopidogrel formulations in patients that had undergone PCI with DES.

Erratum to: Additive Beneficial Effects of Valsartan Combined with Rosuvastatin in the Treatment of Hypercholesterolemic Hypertensive Patients.

[This corrects the article on p. 225 in vol. 45, PMID: 26023311.].

Impact of Gender on the Association of Epicardial Fat Thickness, Obesity, and Circadian Blood Pressure Pattern in Hypertensive Patients.

This study aimed to investigate the effects of gender on the association between epicardial fat thickness (EFT) and circadian blood pressure (BP) changes in patients with recently diagnosed essential hypertension (EH). A total of 441 patients with EH (male/female: 236/205, mean age: 50.7 ± 13.8) and 83 control patients underwent 24-hour ambulatory BP monitoring and echocardiography. Obese EH patients had higher circadian BP profile with BP variability, wall thickness, and left ventricular mass than nonobese EH patients and controls (all p's <0.05) without gender differences. EFT was higher in female than in male patients (7.0 ± 2.5 versus 5.9 ± 2.2 mm, p < 0.001) and higher in the obese female EH group (7.5 ± 2.6 mm) than in the control (6.4 ± 2.8 mm) or nonobese EH group (6.7 ± 2.8 mm) among women, whereas EFT did not vary among males (5.9 ± 1.9 versus 6.0 ± 2.7 versus 5.9 ± 2.4 mm, p = 0.937). Multivariate logistic regression analysis demonstrated that the 24-hour mean BP variability was associated with SBP (p = 0.018) and EFT (p = 0.016) in female patients, but not in male patients. The relationships among circadian BP variability, obesity, and EFT were affected by gender in different manners. EFT may be a more valuable parameter in the evaluation of BP severity and obesity in women than in men.

Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients.

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.

The Impact of Subclinical Hypothyroidism or Thyroid Autoimmunity on Coronary Vasospasm in Patients without Associated Cardiovascular Risk Factors.

BACKGROUND AND OBJECTIVES: Subclinical hypothyroidism is associated with endothelial dysfunction and impaired coronary flow reserve. However, the effect of subclinical hypothyroidism or thyroid autoimmunity on variant angina has yet to be determined. SUBJECTS AND METHODS: Among 385 consecutive patients without associated cardiovascular risk factors who underwent coronary angiography with the ergonovine provocation test (EPT), 165 had a positive EPT {EPT(+)} and 220 had a negative EPT {EPT(-)}. The relationship between coronary artery spasm and the presence of subclinical thyroid dysfunction as well as serum thyroid peroxidase autoantibody (TPO Ab) was evaluated. RESULTS: The proportion of patients with subclinical hypothyroidism among those who were EPT(+) was significantly higher than that in those who were EPT(-) (18% vs. 11%, p=0.001). However, there was no significant difference in the proportion of patients with subclinical hyperthyroidism between the groups. Moreover, EPT(+) patients showed significantly more positive TPO Ab (33% vs. 14%, p<0.001) than those with EPT(-). There was a positive correlation between EPT(+) and TPO positivity (r=0.226, p<0.001), subclinical hypothyroidism (r=0.112, p=0.033), and body mass index (r=0.123, p=0.018). Binary logistic regression analysis revealed that the significant predictors of EPT(+) were body mass index {adjusted odds ratio (OR)=1.042, 95% confidence interval (CI)=1.005-1.080}, presence of subclinical hypothyroidism (OR=3.047, 95% CI=1.083-8.572), TPO Ab titer (OR=1.028, 95% CI=1.015-1.041), and the presence of TPO Ab (OR=4.904, 95% CI=1.544-15.567). CONCLUSION: Subclinical hypothyroidism and the presence of TPO Ab are significantly associated with coronary vasospasm in patients without cardiovascular risk factors.

The Korean Heart Rhythm Society's 2014 Statement on Antithrombotic Therapy for Patients with Nonvalvular Atrial Fibrillation: Korean Heart Rhythm Society.

In patients with nonvalvular atrial fibrillation (AF), the risk of stroke varies considerably according to individual clinical status. The CHA2DS2-VASc score is better than the CHADS2 score for identifying truly lower risk patients with AF. With the advent of novel oral anticoagulants (NOACs), the strategy for antithrombotic therapy has undergone significant changes due to its superior efficacy, safety and convenience compared with warfarin. Furthermore, new aspects of antithrombotic therapy and risk assessment of stroke have been revealed: the efficacy of stroke prevention with aspirin is weak, while the risk of major bleeding is not significantly different from that of oral anticoagulant (OAC) therapy, especially in the elderly. Reflecting these pivotal aspects, previous guidelines have been updated in recent years by overseas societies and associations. The Korean Heart Rhythm Society has summarized the new evidence and updated recommendations for stroke prevention of patients with nonvalvular AF. First of all, antithrombotic therapy must be considered carefully and incorporate the clinical characteristics and circumstances of each individual patient, especially with regards to balancing the benefits of stroke prevention with the risk of bleeding, recommending the CHA2DS2-VASc score rather than the CHADS2 score for assessing the risk of stroke, and employing the HAS-BLED score to validate bleeding risk. In patients with truly low risk (lone AF, CHA2DS2-VASc score of 0), no antithrombotic therapy is recommended, whereas OAC therapy, including warfarin (international normalized ratio 2-3) or NOACs, is recommended for patients with a CHA2DS2-VASc score ≥2 unless contraindicated. In patients with a CHA2DS2-VASc score of 1, OAC therapy should be preferentially considered, but depending on bleeding risk or patient preferences, antiplatelet therapy or no therapy could be permitted.