Abstract Purpose The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for ...a future single-pill combination formulation. Methods This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure SiDBP between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. Findings 420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, –6.0 (8.5) mm Hg; amlodipine 5 mg, –10.6 (9.2) mm Hg; amlodipine 10 mg, –15.9 (7.2) mm Hg; fimasartan 30 mg, –10.1 (9.1) mm Hg; fimasartan 60 mg, –13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, –16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, –19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, –16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, –21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups ( P = 0.0884). The most common AE was headache (12 patients 2.9%), followed by dizziness (11 patients 2.6%) and elevated blood creatine phosphokinase levels (6 patients 1.4%). Implications Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Purpose The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk. Methods This was a ...12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 337 patients were screened. After a 4-week run-in period, 245 of these patients with high or moderately high risk as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines were randomly assigned. Patients received 1 of 6 regimens for 8 weeks as follows: (1) rosuvastatin 5 mg, (2) rosuvastatin 5 mg/ezetimibe 10 mg, (3) rosuvastatin 10 mg, (4) rosuvastatin 10 mg/ezetimibe 10 mg, (5) rosuvastatin 20 mg, or (6) rosuvastatin 20 mg/ezetimibe 10 mg. The primary outcome variable was percentage change in the level of LDL-C at week 8 of drug treatment. Secondary outcome variables included percentage changes of other lipid variables and achievement rates of LDL-C targets. Tolerability analyses were also performed. Findings The percentage change of LDL-C ranged from –45% to –56% (mean, –51%) in the monotherapy groups and from –58% to –63% (mean, –60%) in the combination therapy groups. The percentage change was greater in the pooled combination therapy group than in the counterpart ( P < 0.001 for the pooled groups); this difference was more obvious for regimens with a lower statin dose. The percentage reductions of total cholesterol and triglycerides were greater in the combination groups than in the monotherapy groups. The LDL-C target achievement rates were 64% to 87% (mean, 73%) in the monotherapy groups and 87% to 95% (mean, 91%) in the combination groups ( P = 0.01 for the pooled groups). The rates were significantly greater in patients receiving the combination therapy than in the monotherapy at lower doses of rosuvastatin. The proportions of patients with various adverse events were not significantly different between the groups. Implications Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background Video-assisted thoracoscopic surgery (VATS) is widely performed in patients with resectable non-small cell lung cancer. However, it is unknown whether VATS sublobar resection has ...advantages compared with VATS lobectomy in preserving pulmonary function. Methods Three hundred patients with non-small cell lung cancer who underwent VATS were enrolled. Pulmonary function tests were performed three times: preoperatively, and at 3 and 12 months postoperatively. Pulmonary function was compared between the VATS lobectomy group (n = 227) and the VATS sublobar resection group (n = 73). Results The VATS sublobar resection group had greater preserved pulmonary function than the VATS lobectomy group at 3 and 12 months postoperatively ( p < 0.001). However, a VATS lobectomy of the right upper or right middle lobe revealed no difference in forced vital capacity (−1.21% versus −1.45%; p = 0.88) or the diffusion capacity of carbon monoxide (−3.99% versus −2.45%; p = 0.61) compared with VATS sublobar resection after 12 months. In those who underwent VATS of the right lower lobe, forced expiratory volume in 1 second (−8.60% versus −3.69%; p = 0.12) was not different between the two groups after 12 months. Video-assisted thoracoscopic surgery lobectomy of the left upper or left lower lobe resulted in lower pulmonary function than VATS sublobar resection ( p < 0.05). Conclusions Patients with non-small cell lung cancer who underwent VATS sublobar resection demonstrated greater pulmonary function than those who underwent VATS lobectomy. However, in right-side VATS lobectomy, some differences dissipated at 1 year.
Objectives The object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) ...national database, as well as to provide an overview of the RA patients who are currently registered in KORONA. Methods The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database. Results A total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010. Conclusions KORONA is the first nationwide Korean RA-specific cohort and it will provide valuable “real-world” information for Korean RA patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Objective This study was performed to investigate the association of red cell distribution width (RDW) with 28-day mortality in patients with severe sepsis and septic shock. Methods We ...performed a retrospective analysis of patients with severe sepsis and septic shock. Patients' demographic data, comorbidities, the blood test results including RDW at admission to the emergency department, and Acute Physiologic and Chronic Health Evaluation II score were compared between 28-day survivors and nonsurvivors. Red cell distribution width was categorized into tertiles as 14% or less, 14.1% to 15.7%, and 15.8% or greater. Multivariate Cox proportional hazards regression analysis was performed to determine the risk factors for mortality. Results A total of 566 patients were included, and overall mortality was 29%. Red cell distribution width was significantly higher in nonsurvivors than in survivors, and the corresponding mortality of patients with an RDW of 14% or less, 14.1% to 15.7%, and 15.8% or greater was 13.1%, 30.1%, and 44.9%, respectively ( P < .001). In Cox proportional hazards analysis, groups with higher RDW are independently associated with 28-day mortality compared with groups with an RDW of 14.0% or less: RDW 14.1% to 15.7% (hazard ratio, 1.66; 95% confidence interval CI, 1.00-2.76) and RDW of 15.8% or greater (hazard ratio, 2.57; 95% CI, 1.53-4.34). The area under the receiver operating curve of RDW was 0.68 (95% CI, 0.63-0.72). Conclusion Red cell distribution width is associated with 28-day mortality in patients with severe sepsis and septic shock.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There have been several reports showing that the statin use is associated with new-onset diabetes mellitus (DM). The aim of the present study was to evaluate the impact of chronic statin use on ...development of new-onset DM in a series of Asian population. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2010. A total of 10,994 patients without a history of diabetes were analyzed. Baseline lipid profiles, fasting glucose, Hemoglobin (Hb) A1c, and glucose tolerance tests were measured in all patients before statin treatment. Included patients had HbA1c ≤5.7% and fasting glucose level ≤100 (mg/dl). The patients were divided into 2 groups according to the use of statins (the statin group, n = 2,324 patients and the nonstatin group, n = 8,670 patients). To adjust baseline potential confounders, a propensity score–matched analysis was performed using logistic regression model. After propensity score matching, 2 propensity-matched groups (1,699 pairs, n = 3,398, C statistic = 0.859) were generated and analyzed. After propensity score matching, baseline characteristics of both groups were balanced except that the statin group was older and had higher rate of coronary artery disease compared with the nonstatin group. During a 3-year follow-up, the statin group had higher incidence of new-onset DM compared with the nonstatin group (hazard ratio 1.99, 95% CI 1.36 to 2.92, p <0.001), but the statin group showed lower incidence of major adverse cerebral-cardiovascular events compared with the nonstatin group (hazard ratio 0.40, 95% CI 0.19 to 0.85, p <0.001). In the present study, although the use of statins was associated with higher rate of new-onset DM, it markedly improved 3-year cardiovascular outcomes in Asian population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Skin cancer is the most common malignancy to arise after organ transplantation in Caucasians, but limited data are available on its incidence in Asian transplant recipients. Objective We ...sought to assess the incidence of skin cancer after organ transplantation in a Korean cohort. Methods A cohort study was conducted to determine the incidence and risk factors for skin cancers among kidney, liver, heart, or pancreas transplant recipients, treated at the Asan Medical Center in Seoul, Korea. Results The cumulative incidences of skin cancer were 0.70% at 5 years, 1.66% at 10 years, and 2.31% at 15 years. For all skin cancers, squamous cell carcinoma, basal cell carcinoma, and Kaposi sarcoma, the standardized incidence ratios between the recipients and the Korean general population were 30.9 (95% confidence interval, 12.4-63.6), 61.9 (12.8-180.8), 11.9 (0.3-66.1), and 565.2 (68.4-2041.6) after the end of the fifth posttransplantation year, respectively. Limitations We cannot exclude the possibility of both the underestimation because of potential missing cases and the overestimation because of the ascertainment bias. Conclusion The incidence of posttransplantation skin cancer is very low in Korean patients. However, the risk of skin cancer in organ transplant recipients may be considerably higher than that in the Korean general population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Purpose The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension. ...Methods Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). Findings Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were −2.0 (8.8) mm Hg in the L10 group, −6.7 (8.5) mm Hg in L10/V80 group, and −8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was −4.6 mm Hg (95% CI, −6.5 to −2.6; P < 0.001) in the L10/V80 group and −5.9 mm Hg (95% CI, −7.9 to −4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were −5.6 (7.9)/−8.0 (12.0) mm Hg and −5.5 (7.0)/−8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. Implications Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Stenting for bifurcation lesions is still challenging, and the effect of intravascular ultrasound (IVUS) guidance on long-term outcomes has not been evaluated. We assessed the long-term outcomes of ...IVUS-guided stenting in bifurcation lesions. We evaluated 758 patients with de novo nonleft main coronary bifurcation lesions who underwent stent implantation from January 1998 to February 2006. We compared the adverse outcomes (i.e., death, stent thrombosis, and target lesion revascularization) within 4 years, after adjustment using a multivariate Cox proportional hazard model and propensity scoring. IVUS-guided stenting significantly reduced the long-term all-cause mortality (hazard ratio HR 0.31, 95% confidence interval CI 0.13 to 0.74, p = 0.008) in the total population and in the patients receiving drug-eluting stents (DESs) (HR 0.24, 95% CI 0.06 to 0.86, p = 0.03), but not in the patients receiving bare metal stents (HR 0.41, 95% CI 0.13 to 1.26, p = 0.12). IVUS-guided stenting had no effect on the rate of stent thrombosis (HR 0.48, 95% CI 0.16 to 1.43, p = 0.19) or target lesion revascularization (HR 1.47, 95% CI 0.79 to 2.71, p = 0.21). In patients receiving DESs, however, IVUS guidance reduced the development of very late stent thrombosis (0.4% vs 2.8%, p = 0.03, log-rank test). In conclusion, in patients receiving DESs, IVUS-guided stenting for treatment of bifurcation lesions significantly reduced the 4-year mortality compared to conventional angiographically guided stenting. In addition, IVUS guidance reduced the development of very late stent thrombosis in patients receiving DESs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
