1.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
2.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
3.Cilostazol and Probucol for Cognitive Decline after Stroke: A Cognitive Outcome Substudy of the PICASSO Trial
Jae-Sung LIM ; Sun U. KWON ; Kyung-Ho YU ; Sungwook YU ; Jong-Ho PARK ; Byung-Chul LEE ; Mi Sun OH ; Yong-Jae KIM ; Joung-Ho RHA ; Yang-Ha HWANG ; Ji Sung LEE ; Sung Hyuk HEO ; Seong Hwan AHN ; Woo-Keun SEO ; Jong-Moo PARK ; Ju-Hun LEE ; Jee-Hyun KWON ; Sung-Il SOHN ; Jin-Man JUNG ; Hahn Young KIM ; Eung-Gyu KIM ; Jae-Kwan CHA ; Man-Seok PARK ; Hyo Suk NAM ; Hee-Joon BAE ; Dong-Eog KIM ; Jaeseol PARK ; Yeonwook KANG ; Jimi CHOI ; Juneyoung LEE
Journal of Stroke 2021;23(1):128-131
4.Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial
Eun-Jae LEE ; Sun U. KWON ; Jong-Ho PARK ; Yong-Jae KIM ; Keun-Sik HONG ; Sungwook YU ; Yang-Ha HWANG ; Ji Sung LEE ; Juneyoung LEE ; Joung-Ho RHA ; Sung Hyuk HEO ; Sung Hwan AHN ; Woo-Keun SEO ; Jong-Moo PARK ; Ju-Hun LEE ; Jee-Hyun KWON ; Sung-Il SOHN ; Jin-Man JUNG ; Hahn Young KIM ; Eung-Gyu KIM ; Sung Hun KIM ; Jae-Kwan CHA ; Man-Seok PARK ; Hyo Suk NAM ; Dong-Wha KANG ;
Journal of Stroke 2020;22(1):108-118
Background:
and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study.
Methods:
Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm.
Results:
One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint.
Conclusions
Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.
5.Impact of Continuous Care on Health Outcomes and Cost for Type 2 Diabetes Mellitus: Analysis Using National Health Insurance Cohort Database
Ji Hyun NAM ; Changwoo LEE ; Nayoung KIM ; Keun Young PARK ; Jeonghoon HA ; Jaemoon YUN ; Dong Wook SHIN ; Euichul SHIN
Diabetes & Metabolism Journal 2019;43(6):776-784
BACKGROUND: The objective of the study was to determine the impact of continuous care on health outcomes and cost of type 2 diabetes mellitus (T2DM) in Korea.METHODS: A nationwide retrospective, observational case-control study was conducted. Continuity of treatment was measured using Continuity of Care (COC) score. Information of all patients newly diagnosed with T2DM in 2004 was retrieved from the National Health Insurance database for the period of 2002 to 2013. The study examined 2,373 patients after applying exclusion criteria, such as for patients who died from conditions not related to T2DM. Statistical analyses were performed using frequency distribution, simple analysis (t-test and chi-squared test), and multi-method analysis (simple linear regression, logistic regression, and survival analysis).RESULTS: The overall COC score was 0.8±0.24. The average incidence of diabetic complications was 0.39 per patient with a higher COC score, whereas it was 0.49 per patient with a lower COC score. In both survival and logistic analyses, patients who had high COC score were significantly less likely to have diabetic complications (hazard ratio, 0.69; 95% confidence interval, 0.54 to 0.88). The average medical cost was approximately 3,496 United States dollar (USD) per patient for patients with a higher COC score, whereas it was 3,973 USD per patient for patients with a lower COC score during the 2006 to 2013 period, with a difference of around 477 USD, which is statistically significant after adjusting for other factors (β=−0.152).CONCLUSION: Continuity of care for diabetes significantly reduced health complications and medical costs from patients with T2DM.
Case-Control Studies
;
Cohort Studies
;
Continuity of Patient Care
;
Diabetes Complications
;
Diabetes Mellitus, Type 2
;
Humans
;
Incidence
;
Korea
;
Linear Models
;
Logistic Models
;
National Health Programs
;
Retrospective Studies
;
United States
6.Long-term rivaroxaban for the treatment of acute venous thromboembolism in patients with active cancer in a prospective multicenter trial
Ho Young YHIM ; Won Il CHOI ; Sung Hyun KIM ; Seung Hyun NAM ; Kyoung Ha KIM ; Yeung Chul MUN ; Doyeun OH ; Hun Gyu HWANG ; Keun Wook LEE ; Eun Kee SONG ; Yong Shik KWON ; Soo Mee BANG
The Korean Journal of Internal Medicine 2019;34(5):1125-1135
BACKGROUND/AIMS:
Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients.
METHODS:
In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication.
RESULTS:
Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died.
CONCLUSIONS
Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.
7.Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping.
Sang Won HAN ; Yong Jae KIM ; Seong Hwan AHN ; Woo Keun SEO ; Sungwook YU ; Seung Hun OH ; Hyo Suk NAM ; Hye Yeon CHOI ; Sung Sang YOON ; Seo Hyun KIM ; Jong Yun LEE ; Jun Hong LEE ; Yang Ha HWANG ; Kee Ook LEE ; Yo Han JUNG ; Jun LEE ; Sung Il SOHN ; Youn Nam KIM ; Kyung A LEE ; Cheryl D BUSHNELL ; Kyung Yul LEE
Journal of Stroke 2017;19(3):356-364
BACKGROUND AND PURPOSE: To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms. METHODS: This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke. RESULTS: The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60–2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26–1.79). CONCLUSIONS: Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.
Cytochrome P-450 CYP2C19
;
Cytochrome P-450 Enzyme System*
;
Cytochromes*
;
Genotype
;
Humans
;
Metabolism
;
Platelet Aggregation Inhibitors
;
Prospective Studies
;
Random Allocation
;
Recurrence
;
Sample Size
;
Secondary Prevention*
;
Stroke*
8.Importance of Specimen Type and Quality in Diagnosing Middle East Respiratory Syndrome.
Hee Jae HUH ; Jae Hoon KO ; Young Eun KIM ; Chang Hun PARK ; Geehay HONG ; Rihwa CHOI ; Shinae YU ; Sun Young CHO ; Ji Man KANG ; Myoung Keun LEE ; Chang Seok KI ; Eun Suk KANG ; Nam Yong LEE ; Jong Won KIM ; Yae Jean KIM ; Young Eun HA ; Cheol In KANG ; Doo Ryeon CHUNG ; Kyong Ran PECK ; Jae Hoon SONG
Annals of Laboratory Medicine 2017;37(1):81-83
9.Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction.
Doo Sun SIM ; Myung Ho JEONG ; Ho Chun SONG ; Jahae KIM ; Ari CHONG ; Hee Seung BOM ; In Seok JEONG ; Sang Gi OH ; Jong Min KIM ; Dae Sung PARK ; Jung Ha KIM ; Kyung Seob LIM ; Min Suk KIM ; Shi Hyun RYU ; Hyun Kuk KIM ; Sung Soo KIM ; Su Young JANG ; Jae Yeong CHO ; Hae Chang JEONG ; Ki Hong LEE ; Keun Ho PARK ; Nam Sik YOON ; Hyun Ju YOON ; Kye Hun KIM ; Young Joon HONG ; Hyung Wook PARK ; Ju Han KIM ; Youngkeun AHN ; Jeong Gwan CHO ; Jong Chun PARK ; Jung Chaee KANG
Journal of Korean Medical Science 2015;30(1):34-43
Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
3-Iodobenzylguanidine
;
Angiotensin II Type 1 Receptor Blockers/therapeutic use
;
Angiotensin Receptor Antagonists/*therapeutic use
;
Angiotensin-Converting Enzyme Inhibitors/therapeutic use
;
Animals
;
Anterior Wall Myocardial Infarction/*drug therapy/physiopathology
;
Biphenyl Compounds/*therapeutic use
;
Cardiotonic Agents/*therapeutic use
;
Disease Models, Animal
;
Echocardiography
;
Fluorodeoxyglucose F18
;
Perindopril/therapeutic use
;
Positron-Emission Tomography
;
Pyrimidines/*therapeutic use
;
Random Allocation
;
Swine
;
Tetrazoles/*therapeutic use
;
Tomography, Emission-Computed, Single-Photon
;
Valsartan/therapeutic use
;
Ventricular Function, Left/*physiology
10.Comparison of Coronary Plaque and Stenosis Between Coronary Computed Tomography Angiography and Virtual Histology-Intravascular Ultrasound in Asymptomatic Patients with Risk Factors for Coronary Artery Disease.
Young Joon HONG ; Myung Ho JEONG ; Yun Ha CHOI ; Soo Young PARK ; Hyun Ju SEON ; Hyun Sung LEE ; Yun Hyun KIM ; Sang Cheol CHO ; Jae Young CHO ; Hae Chang JEONG ; Soo Young JANG ; Jong Hyun YOO ; Ji Eun SONG ; Ki Hong LEE ; Keun Ho PARK ; Doo Sun SIM ; Nam Sik YOON ; Hyun Ju YOON ; Kye Hun KIM ; Hyung Wook PARK ; Ju Han KIM ; Youngkeun AHN ; Jeong Gwan CHO ; Jong Chun PARK ; Jung Chaee KANG
Journal of Lipid and Atherosclerosis 2014;3(2):79-87
OBJECTIVES: The purpose of the study was to compare plaque characteristics by coronary computed tomography angiography (CCTA) with those by virtual histology-intravascular ultrasound (VH-IVUS). METHODS: We enrolled 50 asymptomatic patients with diabetes mellitus or more than two risk factors for coronary artery disease such as hypertension, smoking, and hyperlipidemia. If the patient had a coronary lesion (plaque with more than 50% stenosis or calcium score more than 100), we recommended coronary angiography and VH-IVUS and compared CCTA findings with VH-IVUS findings. RESULTS: 35 patients (70%) had coronary lesions, and we performed both CCTA and VH-IVUS in 23 patients. All 23 patients had multiple risk factors, and the majority of target lesions were located at left anterior descending artery (73.9%), and calcium score of lesion site was 106+/-162 with plaque volume of 232+/-153 mm3 by CCTA. Calcium score of lesion site was significantly greater in diabetic patients (n=14) than non-diabetic patients (n=9) (118+/-159 vs. 88+/-175, p=0.038). By VH-IVUS, plaque volume was 174+/-127 mm3, absolute necrotic core (NC) volume was 22+/-21 mm3, and relative NC volume was 20.8+/-8.7%. Absolute dense calcium (DC) volume and absolute NC volumes were significantly greater in diabetic patients than non-diabetic patients (11.5+/-13.8 mm3 vs. 9.1+/-11.0 mm3, p=0.028, and 23.9+/-24.7 mm3 vs. 18.1+/-14.3 mm3, p=0.035, respectively). Plaque volume by CCTA correlated with that of VH-IVUS (r=0.742, p<0.001), and plaque volume by CCTA correlated with absolute NC volume by VH-IVUS (r=0.621, p<0.001), and calcium score of lesion site by CCTA correlated with absolute dense calcium volume by VH-IVUS (r=0.478, p=0.028). CONCLUSION: Coronary lesion was detected by CCTA in 70% of asymptomatic patients with multiple coronary risk factors, and parameters detected by CCTA correlated well with those detected by VH-IVUS.
Angiography*
;
Arteries
;
Calcium
;
Constriction, Pathologic*
;
Coronary Angiography
;
Coronary Artery Disease*
;
Diabetes Mellitus
;
Humans
;
Hyperlipidemias
;
Hypertension
;
Risk Factors*
;
Smoke
;
Smoking
;
Ultrasonography*

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