Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

Public Reporting on the Quality of Care in Patients with Acute Myocardial Infarction: The Korean Experience.

Public reporting is a way to promote quality of healthcare. However, evidence supporting improved quality of care using public reporting in patients with acute myocardial infarction (AMI) is disputed. This study aims to describe the impact of public reporting of AMI care on hospital quality improvement in Korea. Patients with AMI admitted to the emergency room with ICD-10 codes of I21.0 to I21.9 as the primary or secondary diagnosis were identified from the national health insurance claims data (2007-2012). Between 2007 and 2012, 43,240/83,378 (51.9%) patients manifested ST segment elevation myocardial infarction (STEMI). Timely reperfusion rate increased (ß = 2.78, p = 0.001). The mortality rate of STEMI patients was not changed (ß = -0.0098, p = 0.384) but that of NSTEMI patients decreased (ß = -0.465, p = 0.001). Public reporting has a substantial impact on the process indicators of AMI in Korea because of the increased reperfusion rate. However, the outcome indicators such as mortality did not significantly change, suggesting that public reporting did not necessarily improve the quality of care.

Prediction of Judkins Left Catheter Size during Left Transradial Coronary Angiography by Simple Chest Radiographic and Echocardiographic Index.

Background and Objectives: Appropriate catheter selection when conducting transradial coronary angiography (CAG) helps shorten examination time, preventing vascular complications and lowering medical expense. However, catheter selection is made based on the practitioner's experience in almost all cases. Therefore, we undertook this study to define radiologic and echocardiographic indices that would enable physicians to anticipate appropriate catheter selection. Materials and Methods: This is a retrospective study of 244 undergoing transradial diagnostic CAG at an established center from February 2006 to April 2014. Patients who successfully underwent angiography with a JL3.5 catheter were defined as the control group, and patients who successfully underwent angiography after the catheter was replaced with a JL4.0 or higher were defined as the switched group. To identify predictors for appropriate catheter selection, radiologic and echocardiographic indices were analyzed. Results: A total of 122 patients in the switched group and 122 patients in the control group were analyzed in this study. Average age was 64.65 ± 8.6 years. In the radiographic index, the switched group exhibited a significantly higher mediastinal-thoracic ratio (0.27 ± 0.05 vs. 0.23 ± 0.03, p < 0.001. Additionally, the mediastinal-cardiac ratio was significantly greater in the switched group (0.50 ± 0.08 vs. 0.45 ± 0.05, p < 0.001). Aortic root diameter, which is used here as the echocardiographic index, was significantly larger in the switched group compared to the control group (34.94 ± 4.18 mm vs. 32.66 ± 3.99 mm, p < 0.001). In the multivariable logistic regression model, mediastinal-cardiac ratio (OR 5.197, 95% CI 2.608-10.355, p < 0.001) and increased aortic root (OR 2.115, 95% CI 1.144-3.912, p = 0.017) were significantly associated with catheter change. Conclusions: Mediastinal-cardiac ratio and aortic root diameter provide helpful and effective indices for appropriate catheter selection during transradial coronary angiography.

Clinical characteristics and outcomes of infective endocarditis: impact of haemodialysis status, especially vascular access infection on short-term mortality.

BACKGROUND: Patients on haemodialysis (HD) are at high risk of infective endocarditis (IE). Research comparing the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE is limited. Specifically, no data focussed on vascular access infections (VAIs) have been reported. METHODS: The medical records of patients with IE were retrospectively reviewed from January 2010 to February 2020 in a referral hospital in Korea. Those with definite or possible IE by modified Duke criteria were included in the study. The clinical characteristics, microbiological features, echocardiographic findings and outcomes of the patients were analysed. RESULTS: Of the 80 patients with IE, 34 had undergone HD and 46 had not. HD patients with IE had a higher in-hospital mortality rate (50% vs. 17.4%, p = .004) than non-HD patients. In multivariable stepwise Cox proportional hazards regression analysis, HD (hazard ratio = 2.633; 95% confidential interval: 1.053-6.582; p = .038) was predictors of 60-day mortality in IE patients. In HD patients, the presence of VAI was associated with a high in-hospital mortality rate (70.59% vs. 29.41%, p = .039) and all of the patients with VAIs (100%) had methicillin-resistant S. aureus (MRSA) as a causative pathogen. CONCLUSIONS: HD patients with IE showed high in-hospital mortality. HD, high C-reactive protein levels and lower left ventricular ejection fraction were predictors of 60-day mortality in IE patients. In particular, HD patients with VAIs had higher mortality rates and MRSA should be considered as the causative microorganism.

Neutrophil-Lymphocyte Ratio as a Predictor of Venous Thromboembolism after Total Knee Replacement.

Venous thromboembolism (VTE) is a potentially serious complication after total knee replacement (TKR), and recent guideline recommends thromboprophylaxis for VTE after TKR. The neutrophil-lymphocyte ratio (NLR) has emerged as a simple and new prognostic biomarker for several cardiovascular diseases. This study was performed to investigate the precise incidence of postoperative VTE and the role of NLR for predicting VTE in patients receiving thromboprophylaxis after TKR. We retrospectively enrolled 264 patients undergoing TKR who underwent routine screening enhanced pulmonary artery and lower extremity venography computed tomography (CT) scan within 7 postoperative days. Biochemical tests were performed within 2 weeks prior to surgery, and the NLR was defined as the absolute neutrophil count in peripheral blood divided by lymphocyte count. All patients received thromboprophylaxis with enoxaparin postoperatively. Of 264 patients, 102 (38.6%) were diagnosed with deep vein thrombosis (DVT) or pulmonary embolism on CT scan. Preoperative NLR was significantly higher in patients with postoperative VTE compared with that in patients without VTE (2.57 ± 1.59 vs. 2.11 ± 1.10, p = 0.011). Receiver operating characteristic curve analysis showed that a preoperative NLR of 1.90 was the best cutoff value for the prediction of postoperative VTE (sensitivity 57.8%, specificity 55.6%, and area under curve 0.589). In the multivariate analysis, a preoperative NLR ≥1.90 was a sole independent predictor of postoperative VTE (odds ratio: 1.95, 95% computed tomography: 1.16-3.31, p = 0.013). The present study shows a higher incidence of VTE (38.6%) after TKR in patients receiving thromboprophylaxis than that reported in previous studies. Furthermore, preoperative NLR was significantly higher in patients with postoperative VTE, and a high preoperative NLR (≥1.90) was an independent predictor of VTE after TKR. NLR measurement may be a simple and useful method for the prediction of VTE in patients undergoing TKR.

Association of low T3 level with increased in-hospital mortality in patients with stress cardiomyopathy.

BACKGROUND: Stress cardiomyopathy (SCMP) is an acute but reversible heart failure syndrome with varying clinical outcomes. Although low triiodothyronine (T3) levels are closely associated with heart failure, it is uncertain whether total T3 levels on admission might be correlated with clinical outcomes in patients with SCMP. The aim of this study was to investigate the prognostic value of total T3 level for in-hospital mortality in patients with SCMP. METHODS: Patients presenting with SCMP at a single tertiary hospital between January 2013 and May 2019 were retrospectively reviewed. The diagnosis of SCMP was confirmed using the International Takotsubo Diagnostic Criteria and echocardiography was performed at least twice at the time of admission. Comorbidities, antecedent triggers, and other cardiac and metabolic parameters were measured in the survivor group compared with the non-survivor group. We evaluated the correlation between these parameters, especially total T3 and the prevalence of in-hospital mortality and the predictive values of total T3. RESULTS: Of the 134 SCMP patients (69.4 ± 15.5 years old, 94 women), 29 (21.6%) died during hospitalisation. The median follow-up period (interquartile range) was 480 days (63.25-1052.50). Total T3 levels were significantly lower in the non-survival group than in the survival group (33.38 ± 22.58 ng/dL vs. 65.72 ± 34.68 ng/dL, p < 0.0001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤64.37 ng/dL) for in-hospital mortality (area under curve [AUC] = 0.764, p < 0.001). In multivariable analysis, the T3 level (odds ratio [OR], 0.957; 95% confidential interval [CI], 0.934 to 0.982; p < 0.001), left ventricular ejection in follow-up echocardiography (OR, 0.935; 95% CI, 0.889-0.983; p = 0.008), and shock at initial presentation (OR, 3.389; 95% CI, 1.076-10.669; p = 0.037) were independent predictors for in-hospital mortality in SCMP patients. In patients with low T3 (<64.37 ng/dL), the 30-day survival rate was also significantly lower (81.58 vs. 100%, Log rank p = 0.001). CONCLUSIONS: Lower levels of total T3 were strongly correlated with in-hospital mortality in patients with SCMP. A low T3 level might suggest poor prognosis in patients with SCMP.

Impact of Hospital Volume of Percutaneous Coronary Intervention (PCI) on In-Hospital Outcomes in Patients with Acute Myocardial Infarction: Based on the 2014 Cohort of the Korean Percutaneous Coronary Intervention (K-PCI) Registry.

BACKGROUND AND OBJECTIVES: The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes. METHODS: We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI. RESULTS: Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE. CONCLUSIONS: Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry.

Role and Prognosis of Extracorporeal Life Support in Patients Who Develop Cardiac Arrest during or after Office-Based Cosmetic Surgery.

BACKGROUND: Cardiac arrest during or after office-based cosmetic surgery is rare, and little is known about its prognosis. We assessed the clinical outcomes of patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics. METHODS: Between May 2009 and May 2016, 32 patients who developed cardiac arrest during or after treatment at cosmetic surgery clinics were consecutively enrolled. We compared clinical outcomes, including complications, between survivors (n=19) and non-survivors (n=13) and attempted to determine the prognostic factors of mortality. RESULTS: All 32 of the patients were female, with a mean age of 30.40±11.87 years. Of the 32 patients, 13 (41%) died. Extracorporeal life support (ECLS) was applied in a greater percentage of non-survivors than survivors (92.3% vs. 47.4%, respectively; p=0.009). The mean duration of in-hospital cardiopulmonary resuscitation (CPR) was longer for the non-survivors than the survivors (31.55±33 minutes vs. 7.59±9.07 minutes, respectively; p=0.01). The mean Acute Physiology and Chronic Health Evaluation score was also higher among non-survivors than survivors (23.85±6.68 vs. 16.79±7.44, respectively; p=0.01). No predictor of death was identified in the patients for whom ECLS was applied. Of the 19 survivors, 10 (52.6%) had hypoxic brain damage, and 1 (5.3%) had permanent lower leg ischemia. Logistic regression analyses revealed that the estimated glomerular filtration rate was a predictor of mortality. CONCLUSION: Patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics experienced poor prognoses, even though ECLS was applied in most cases. The survivors suffered serious complications. Careful monitoring of subjects and active CPR (when necessary) in cosmetic surgery clinics may be essential.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

Randomized Comparison of Everolimus- and Zotarolimus-Eluting Coronary Stents With Biolimus-Eluting Stents in All-Comer Patients.

BACKGROUND: There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES). METHODS: This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively. RESULTS: Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference -1.4% [upper limit of 1-sided 95% CI: -3.2%]; Pfor noninferiority <0.001; BES versus ZES: absolute risk difference -1.7% [upper limit of 1-sided 95% CI: -3.6%]; Pfor noninferiority <0.001). CONCLUSIONS: The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01397175.

Impact of Overweight/Obesity on Clinical Outcomes of Patient with Vasospastic Angina: From the Vasospastic Angina in Korea Registry.

Obesity is associated with a high risk of morbidity and mortality in the general population and is a major independent risk factor for cardiovascular disease. We sought to evaluate the effect of overweight/obesity on clinical outcomes of patients with vasospastic angina (VA) at 1-year follow-up. The VA-KOREA (Vasospastic Angina in Korea) registry was a cohort of 11 centers from 2010 to 2015. The primary endpoint was a composite of cardiac death (CD), new-onset arrhythmia, and acute coronary syndrome (ACS). Using the body mass index (BMI) cut-off for Asians, 517 patients with definite VA were divided into either an overweight/obese (BMI ≥ 23 kg/m2) group (n = 378) or a normal weight (BMI 18.5-22.9 kg/m2) group (n = 139). The overweight/obese group showed a significantly lower rate of the primary endpoint composite (2.4% vs 7.9%, p = 0.004) and ACS (0.8% vs 4.3%, p = 0.007) than the normal weight group in the crude population. Similarly, in propensity-score matched analysis, the overweight/obese group showed a significantly lower rate of the primary endpoint composite (2.3% vs 8.4%, p = 0.006) and ACS (1.1% vs 4.6%, p = 0.035) than the normal weight group. However, there were no significant differences in CD and new-onset arrhythmia between the two groups in both the crude and propensity-score matched population. Independent predictors of the primary endpoint were overweight/obesity and dyslipidemia. In patients with VA, the overweight/obese group was associated with a favorable 1-year primary endpoint and the difference was mainly driven by the lower rate of ACS compared with the normal weight group.

Efficacy and Safety of Triple Therapy With Telmisartan, Amlodipine, and Rosuvastatin in Patients With Dyslipidemia and Hypertension: The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial.

PURPOSE: Fixed-dose combination therapy with telmisartan, amlodipine, and rosuvastatin is needed in patients with hypertension and dyslipidemia for better adherence and cost-effectiveness than free-equivalent combination therapies. This study aimed to compare the efficacy and safety of combination therapy with telmisartan, amlodipine, and rosuvastatin versus telmisartan plus amlodipine or telmisartan plus rosuvastatin in patients with hypertension and dyslipidemia. METHODS: The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial (J-TAROS-RCT) was an 8-week, multicenter, randomized, double-blind, parallel, Phase III clinical trial conducted at 9 hospitals in Korea. After a run-in period of >4 weeks, patients who fulfilled the criteria of the National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for randomization to receive 1 of 3 treatments for 8 weeks: (1) telmisartan/amlodipine 80 mg/10 mg plus rosuvastatin 20 mg, (2) telmisartan/amlodipine 80 mg/10 mg, or (3) telmisartan 80 mg plus rosuvastatin 20 mg. The primary end point was efficacy evaluation of combination therapy with telmisartan/amlodipine/rosuvastatin by comparing the change in mean sitting systolic blood pressure (msSBP) and mean percentage change in LDL-C from baseline after 8 weeks of treatment. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: Among 148 patients, the changes in msSBP from baseline after 8 weeks of treatment were a mean (SD) of -24.41 (2.38) versus -9.31 (2.36) mm Hg in the telmisartan/amlodipine/rosuvastatin and telmisartan/rosuvastatin groups, respectively. Significantly more participants achieved the target BP at week 8 in the telmisartan/amlodipine/rosuvastatin group (41 patients [87.2%]) than in the telmisartan/rosuvastatin group (24 [50.0%], P < 0.001). The changes in mean (SD) LDL-C at 8 weeks compared with baseline values were -57.59% (11.59%) versus 6.08% (20.98%) in the telmisartan/amlodipine/rosuvastatin and telmisartan/amlodipine groups, respectively. The percentages of patients who achieved the target LDL-C according to their risk factors after 8 weeks of treatment were 97.87% vs 6.12% in the telmisartan/amlodipine/rosuvastatin and the telmisartan/amlodipine groups (P < 0.0001), respectively. No significant differences were found in the incidence of overall AEs and adverse drug reactions, and serious AEs were comparable among 3 groups. IMPLICATIONS: Fixed-dose combinations of telmisartan, amlodipine, and rosuvastatin decreased BP and LDL-C in patients with hypertension and dyslipidemia. The safety and tolerability profiles of fixed-dose telmisartan, amlodipine, and rosuvastatin combination therapy were comparable with those of telmisartan plus amlodipine or telmisartan plus rosuvastatin. ClinicalTrials.gov identifier: NCT03088254.

Left Ventricular Ejection Fraction Predicts Poststroke Cardiovascular Events and Mortality in Patients without Atrial Fibrillation and Coronary Heart Disease.

BACKGROUND AND OBJECTIVES: It is controversial that decreased left ventricular function could predict poststroke outcomes. The purpose of this study is to elucidate whether left ventricular ejection fraction (LVEF) can predict cardiovascular events and mortality in acute ischemic stroke (AIS) without atrial fibrillation (AF) and coronary heart disease (CHD). METHODS: Transthoracic echocardiography was conducted consecutively in patients with AIS or transient ischemic attack at Soonchunhyang University Hospital between January 2008 and July 2016. The clinical data and echocardiographic LVEF of 1,465 patients were reviewed after excluding AF and CHD. Poststroke disability, major adverse cardiac events (MACE; nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) and all-cause mortality during 1 year after index stroke were prospectively captured. Cox proportional hazards regressions analysis were applied adjusting traditional risk factors and potential determinants. RESULTS: The mean follow-up time was 259.9±148.8 days with a total of 29 non-fatal strokes, 3 myocardial infarctions, 33 cardiovascular deaths, and 53 all-cause mortality. The cumulative incidence of MACE and all-cause mortality were significantly higher in the lowest LVEF (<55) group compared with the others (p=0.022 and 0.009). In prediction models, LVEF (per 10%) had hazards ratios of 0.54 (95% confidence interval [CI], 0.36-0.80, p=0.002) for MACE and 0.61 (95% CI, 0.39-0.97, p=0.037) for all-cause mortality. CONCLUSIONS: LVEF could be an independent predictor of cardiovascular events and mortality after AIS in the absence of AF and CHD.

Transradial versus transfemoral intervention in non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention: the Korean transradial intervention registry of 1 285 patients.

INTRODUCTION: Although the implementation of transradial intervention (TRI) has increased over the last few years, there are limited data on the impact of TRI on efficacy and safety in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We sought to compare one-year clinical outcomes and bleeding complications of TRI with those of transfemoral intervention (TFI) in patients with NSTE-ACS. METHODS: The Korean TRI registry was a cohort of 20 centres from 2012 to 2015. The primary efficacy endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiac death (CD), non-fatal myocardial infarction (MI) and repeat revascularisation (RR). Among the 1 319 patients with NSTE-ACS, 1 285 were finally analysed after excluding 34 due to lack of follow-up data. The patients were divided into TRI and TFI groups according to the final access site. RESULTS: At one-year follow up, the TRI group showed a significantly lower rate of MACE, and a marginally significantly lower rate of CD than the TFI group in the crude population. However, in propensity-score matched analysis, the rate of MACE did not differ between the TRI and TFI groups. Regarding bleeding complications, the TRI group was associated with significantly lower rates of major bleeding in both the crude and matched populations. Independent predictors of MACE were chronic kidney disease (CKD) and multi-vessel disease (MVD). CONCLUSIONS: In patients with NSTE-ACS, TRI was associated with favourable one-year clinical outcomes and lower bleeding complications compared to TFI. Independent predictors of MACE were clinical and angiographic profiles (CKD, MVD) rather than vascular access sites.

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

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

Efficacy and Safety of Ezetimibe and Rosuvastatin Combination Therapy Versus Those of Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia. METHODS: This multicenter, randomized, double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study. In the extension study, ezetimibe 10 mg was also administered to subjects who had received rosuvastatin (5, 10, and 20 mg) alone in the main study, and the same treatment was continued for subjects who had received a combination of rosuvastatin with ezetimibe in the main study. FINDINGS: At the end of the main study (week 8), LDL-C levels were significantly lower in subjects receiving combination therapy than in those receiving rosuvastatin monotherapy. Other lipid profiles also significantly improved in the combination therapy group. These improvements continued in the extension study. The combination therapy of rosuvastatin and ezetimibe was generally well tolerated. At the end of the main study, more subjects achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the combination therapy group than in the monotherapy group. The increased dosage of rosuvastatin was also well tolerated in the combination treatment. IMPLICATIONS: Combination therapy of ezetimibe 10 mg with varying doses of rosuvastatin that are commonly used in the clinical field improved the lipid profile and allowed more subjects to reach the LDL-C goal in primary hypercholesterolemia compared with rosuvastatin monotherapy. In addition, the efficacy of the combination therapy was maintained for the extended period. Additional beneficial changes were also achieved with combination therapy even in patients who responded well to rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT03288038.

Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.

PURPOSE: Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. METHODS: This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. FINDINGS: A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. IMPLICATIONS: Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.

A Phase III, Multicenter, Randomized, Double-blind, Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial.

PURPOSE: Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia. METHODS: I-ROSETTE (Ildong ROSuvastatin & ezETimibe for hypercholesTElolemia) was an 8-week, double-blind, multicenter, Phase III randomized controlled trial conducted at 20 hospitals in the Republic of Korea. Patients with hypercholesterolemia who required medical treatment according to National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for participation in the study. Patients were randomly assigned to receive ezetimibe 10 mg/rosuvastatin 20 mg, ezetimibe 10 mg/rosuvastatin 10 mg, ezetimibe 10 mg/rosuvastatin 5 mg, rosuvastatin 20 mg, rosuvastatin 10 mg, or rosuvastatin 5 mg in a 1:1:1:1:1:1 ratio. The primary end point was the difference in the mean percent change from baseline in LDL-C level after 8 weeks of treatment between the ezetimibe/rosuvastatin and rosuvastatin treatment groups. All patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. FINDINGS: Of 396 patients, 389 with efficacy data were analyzed. Baseline characteristics among 6 groups were similar. After 8 weeks of double-blind treatment, the percent changes in adjusted mean LDL-C levels at week 8 compared with baseline values were -57.0% (2.1%) and -44.4% (2.1%) in the total ezetimibe/rosuvastatin and total rosuvastatin groups, respectively (P < 0.001). The LDL-C-lowering efficacy of each of the ezetimibe/rosuvastatin combinations was superior to that of each of the respective doses of rosuvastatin. The mean percent change in LDL-C level in all ezetimibe/rosuvastatin combination groups was >50%. The number of patients who achieved target LDL-C levels at week 8 was significantly greater in the ezetimibe/rosuvastatin group (180 [92.3%] of 195 patients) than in the rosuvastatin monotherapy group (155 [79.9%] of 194 patients) (P < 0.001). There were no significant differences in the incidence of overall AEs, adverse drug reactions, and serious AEs; laboratory findings, including liver function test results and creatinine kinase levels, were comparable between groups. IMPLICATIONS: Fixed-dose combinations of ezetimibe/rosuvastatin significantly improved lipid profiles in patients with hypercholesterolemia compared with rosuvastatin monotherapy. All groups treated with rosuvastatin and ezetimibe reported a decrease in mean LDL-C level >50%. The safety and tolerability of ezetimibe/rosuvastatin therapy were comparable with those of rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT02749994.