Efficacy and safety of alirocumab in Korean patients with hypercholesterolemia and high cardiovascular risk: subanalysis of the ODYSSEY-KT study

남창욱,김동수,Jianyong Li,Marie T. Baccara-Dinet,Ivy Li,김지현,김종진 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.6

Background/Aims: Efficacy and safety data of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), is not yet well established in the Korean population. We assessed them in ODYSSEY-KT through the pre-specified Korean subanalysis. Methods: In the ODYSSEY-KT study, South Korean and Taiwanese patients with hypercholesterolemia and high cardiovascular risks were randomized (1:1) to alirocumab or placebo. Alirocumab was self-administered subcutaneously at 75 mg every 2 weeks with a maximally tolerated statin dose with or without other lipid- modifying therapies. Alirocumab dose was increased to 150 mg every 2 weeks at week 12 if low density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL at week 8. Primary endpoint was percent change in LDL-C from baseline to week 24. Results from Korean cohort (n = 83: 40 for alirocumab and 43 for placebo, respectively) analyses are reported here. Results: In alirocumab group, the least square of mean change percent in LDL-C levels was –65.7% (placebo: 11.1%; p < 0.0001) and 92.0% of them achieved LDL-C < 70 mg/dL (placebo: 12.7%; p < 0.0001) at week 24. Alirocumab also showed significantly greater improvements in high density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, lipoprotein(a), and apolipoprotein B than placebo (p < 0.05). Two consecutive calculated LDL-C values < 25 mg/dL were observed in 37.5% of alirocumab-treated patients. Overall, 45.0% alirocumab-treated and 51.2% placebo-treated patients experienced treatment-emergent adverse events (TEAEs) without discontinuation of treatment due to TEAEs. Conclusions: Alirocumab has demonstrated to be effective in improvement of LDL-C and related lipid profiles in Korean cohort. Alirocumab was generally well tolerated with no significant safety signals.

정상 성인에서 고주파 초음파도를 이용한 혈관 내피세포의 기능평가: 가령에 따른 기능평가

남창욱,김기식,이상준,이인규 한국심초음파학회 2000 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.8 No.1

연구배경: 혈관 내피세포의 기능 평가에 비침습적인 방법인 고해상도 초음파를 이용한 상완동맥의 혈관 내피세포 의존성 및 비의존성 혈관이완능검사가 많이 이루어지고 있으나 정확한 활성도 평가에 한계가 있어왔으며 저자들은 특수제작된 고정장치를 이용하여 혈관의 활성도가 언제 시작되어 최고치에 이르는지 알아보고, 또한 가령이 내피세포의 기능에 미치는 영향을 확인하였다. 방 법: 건강한 성인 2명을 대상으로 연령별로 두 군으로 나누고, 초음파탐촉자를 고정할 수 있는 특수장치를 이용하여 동일 위치의 혈관변화를 연속 촬영하였다. 검사 30분전부터 침대에서 안정을 시킨 후 상완동맥의 기저치 내경을 측정하고, 혈압계 cuf를 전완 근위부에 착용한 후 300 mHg의 압력으로 상완동맥을 5분간 압박한 후 cuf를 이완시켜 상완동맥에 일시적인 과혈류를 유발하였으며 이후 60초간 내경의 변화를 연속녹화하였다. 이후 15분 뒤에 다시 기저치 내경을 측정하고 니트로글리세린 0.6 mg을 설하로 투여하여 4분간 측정하였다. 결 과: 혈관 내피세포 의존성 혈관이완능검사에서 과혈류 유발에 의한 초기반응은 청년군에서 24.3±2.8초에 발생하고 노년군에서는 28.8±3.6초로 늦게 나타났다. 최고 혈관활성도는 청년군에서 35.5±4.7초에 8.4±1.7%로 나타났고, 노년군에서는 34.5±2.6초에 6.9±1.5%로 청년군에서 혈관의 활성도가 높은 경향이었으나 통계적으로 유의한 차이는 없었다. 혈관 내피세포 비의존성 혈관이완능검사에서 과혈류 유발에 의한 초기반응과 최고 혈관활성도가 나타나는 시기는 유의한 차이가 없었으나 최고 활성도는 청년군에서 19.1±3.1%로 노년군 15.9±2.5%에 비해 유의하게 크게 나타났다. 결 론:노령에 의한 내피세포의 기능장애는 혈관활성의 반응 시간뿐만 아니라 활성의 정도에도 나타난다. 또한 앞으로 진행될 연구에서 혈관 내피세포 의존성 혈관이 완능은 재관류 50초 전후에, 혈관 내피세포 비의존성 혈관이완능은 3분 후에 측정하는 것이 최고 혈관 활성도를 잘 표현한다 하겠으며 혈관의 이완이 30초 이내에 발생하는 것이 정상적인 내피세포의 기능을 가졌다고 평가하겠다. Background and Objectives:Flow-mediated brachial artery vasoactivity has been proposed as a noninvasive means for assessing endothelial function. The present study is designed to assess the influence of aging on endothelial function and when vasoactivity developed initially, peaked. Materials and Method:We measured brachial artery diameter for 60 seconds continuously using 7.5 MHz ultrasound following 5 minutes of lower arm occlusion in 22 normal volun-teers (young group:10 volunteers, 26.5±1.9 years;old group:12 volunteers, 55.9±3.3 years). After sublingual administration of 0.6 mg nitroglycerine, 240 seconds continuously. And then we mea-sure vasoactivity every 3 seconds. Results:Flow-mediated vasodilation (FMD) was started earlier in young group (24.3±2.8 sec;old group 28.8±3.6 sec, p=0.017). After release of occlusion, peak vasoacitivity time was at 35.5±4.7 seconds and peak vasoactivity was 8.4± 1.7% in young group (old group 6.9±1.5%, p=0.099). Endothelial independent vasodilation (EID) was started at 80.7±13.3 seconds after sublingual nitroglycerine in young group (vs 80.0±19.0 sec), peaked at 177.5±16.9 seconds (vs 171.3±13.8 sec). Peak vasoactivity was higher in young group (19.1±3.1%;old group 15.9±2.5%, p=0.033). Conclusion:We conclude that 1) Aging has influence on endothelial function about initiating time of vasoactivity as well as peak vaso- activity. 2) FMD can be measured around 50 seconds after release of brachial artery occlusion and EID at 180 seconds after application of sublingual nitroglycerine. 3) The initiating time of vasoactivity (under 30 seconds) can be used for evaluation of endothelial function.

Fractional Flow Reserve Versus Angiography in Left Circumflex Ostial Intervention After Left Main Crossover Stenting

남창욱,허승호,구본권,도준형,조윤경,박형섭,윤혁준,김형섭,정인성,김윤년,William F. Fearon,탁승제,김권배 대한심장학회 2011 Korean Circulation Journal Vol.41 No.6

Background and Objectives: Discrepancy between angiographic percent (%) diameter stenosis and fractional flow reserve (FFR) exists in non-left main bifurcation lesions. The aim of this study was to compare angiographic stenosis severity and FFR in jailed ostial left circumflex artery (LCX) lesions after left main (LM)-to-left anterior descending artery (LAD) crossover stenting. Subjects and Methods: Twenty-nine (n=29) patients with distal LM or ostial LAD lesions treated by LM-to-LAD crossover stenting were consecutively enrolled. After successful stenting, FFR was measured at the jailed LCX. Additional intervention was performed in lesions with FFR <0.8. Results: The mean reference diameter of LCX was 3.1±0.4 mm, and percent diameter stenosis after crossover stenting was 56±21%. Angiographically significant stenosis (>50%) at the ostial LCX occurred in 59% (17/29) of cases. Among them, only five (29%) lesions had functional significance, and underwent additional procedure. During follow-up, three patients in the deferral group and two patients in the additional intervention group had target lesion revascularization. Conclusion: There was a discrepancy between angiographic percent diameter stenosis and FFR in jailed LCX lesions after LM crossover stenting.

Impact of Optimal Stent Expansion on Late Outcomes after Sirolimus-Eluting Stent Implantation: An Intravascular Ultrasound Study

남창욱,김권배,허승호,조윤경,김경섭,한성욱,김윤년,정인성,이영수,김기식 대한심장학회 2007 Korean Circulation Journal Vol.37 No.6

Background and Objectives:Sirolimus-eluting stents (SESs) have a considerably lower optimal minimal stent area (MSA) threshold compared to bare metal stents (BMSs). In the SIRIUS IVUS sub study, the absolute optimal stent expansion (OSE) of SESs was described as ≥5.0 mm2. The purpose of this study was to evaluate the impact of the OSE on long-term outcomes following SES implantation using absolute IVUS criteria. Subjects and Methods:The study included 157 patients (BMS: 57; SES; 100), who underwent 6-month follow-up angiography and 18-month clinical follow-up after bare metal stent or drug-eluting stent (DES) implantation. According to the absolute measurement IVUS criteria, patients were divided into two groups: OSE and non-OSE. The IVUS criteria for OSE were MSA ≥6.5 mm2 for BMS implantation and MSA ≥5.0 mm2 for SES implantation. Results:Angiographic binary restenosis was higher in the non-OSE than the OSE group with BMS (33.3% vs. 11.4%; p<0.039), but the rates were similar between the two groups with SES (4.5% vs. 3.2%; p=1.00). With the BMS, the MACE rates were 5.7% and 30% in the OSE and non-OSE group, respectively (p=0.017). However, with the SES, the MACE rates were similar between the two groups (OSE group, 3.2% vs. non-OSE group, 4.5%, p=1.00). Conclusion:After SES implantation, there were no significant differences in the late outcomes in relation to the achievement of absolute OSE. A variety of restenosis related factors should be considered for better outcomes after DES implantation. Therefore, the concept of OSE in the era of DESs might need to be revisited. (Korean Circulation J 2007;37:244-250)

Diethylhexyl Phthalate 처치후 건양단이 정자 생성능 및 운동성에 미치는 영향 연구

남창욱,박경수,마진열,Nam, Chang-Uk,Park, Kyeong-Soo,Ma, Jin-Yeul 한국한의학연구원 2006 한국한의학연구원논문집 Vol.12 No.1

We treated KunYangDan (KYK) in SD rats in order toexamine the protective effect against cell damage induced by diethylhexyl phthalate (DEHP). KYD reduced DEHP toxicity by increasing the function of immune cell numbers weight increase of spleen.red blood cells,HB,and HCT content,sperm number and mobility,resulting in improving reproductive function by judging from the recovery of testosterone content. Interestingly the hormone change of testosterone by KYD significantly recovered the decreased its leve. Taken together,these results suggest that KYD specifically affect the reproductive function induced by DEHP,an endocrine disruptor.

Very Late Stent Thrombosis Related to Fracture of a Sirolimus-Eluting Stent

남창욱,김권배,정인성 대한심장학회 2007 Korean Circulation Journal Vol.37 No.8

Although late stent thrombosis is a very rare complication after a drug-eluting stent implantation, this could induce significant sequelae. Several mechanisms for very late stent thrombosis have been suggested. We experienced a new possible mechanism of very late stent thrombosis after the implantation of a sirolimus-eluting stent. A sirolimus-eluting stent fracture might induce mechanical injury of the endothelium and then thrombotic occlusion at 24 months after the stent procedure. (Korean Circulation J 2007;37:385-387)

헤파린 부착 JO 스텐트와 미부착 JO 스텐트 삽입술 후의 장기 추적 성적 비교

남창욱,김권배,김기영,김성열,권택근,이영수,조봉기,손봉준,한성욱,김기식,김윤년 계명대학교 의과학연구소 2000 계명의대학술지 Vol.19 No.2

The risk of acute or subacute closure after angioplasty has been minimized by using stent deployment. However, restenosis rating 20% ∼30% after stenting is still most important limiting factor for stenting. We investigated a long-term effect of implantation of a heparin-coated JO stent compared with the use of un-coated JO steno. Thirty eight patients were assigned heparin-coated JO stent{21 patients, JO(H)} or uncoated JO stent(17 patients, JO). All clinical and angiographic parameters were retrogradely reviewed. They were followed up monthly and performed follow-up coronary angiography 7 months later. The clinical and angiographic parameters were statistically not different between two groups, except hypertension {JO:18%, JO(H):52%, p<0.05}. The reference diameter was 3.12±0.53mm in 10 and 2.85 ±0.43mm in JO(H) (p=0.071). The minimum luminal diameter after stenting was not significantly different{2.91±0.52mm in JO, 2.78±0.42mm in JO(H), p=0.381}. The restenosis rate of JO was 32% and JO(H), 35%(p=0.545). Over seven months follow up, it seems that a strategy of elective stenting with heparin-coated JO stent was not more effective than uncoated JO stent.

The Incidence of Gastro-Esophageal Disease for the Patients with Typical Chest Pain and a Normal Coronary Angiogram

남창욱,김기식,이영수,이상훈,한성욱,허승호,김윤년,김권배,장병국 대한내과학회 2006 The Korean Journal of Internal Medicine Vol.21 No.2

Background : Although patients may present with typical chest pain and exhibit ischemic changes on the cardiac stress test, they are frequently found to have a normal coronary angiogram. Thus, we wanted to determine which procedures should be performed in order to make an adequate diagnosis of the cause of chest pain. Methods : 121 patients (males: 42, 34.7%) who had a normal coronary angiogram with typical chest pain were included in this study. All the patients underwent upper endoscopy, Bernstein’s test and esophageal manometry. Results : Among the 121 patients, clinically stable angina was noted in 107 (88.4%). Stress testing was done in 82 (67.8%); it was positive in 52 (63.4%). Endoscopic findings were erosive gastritis in 18 (14.8%), gastric ulcer in 4 (3.3%), duodenal ulcer in 5 (4.1%), and reflux esophagitis in 16 (13.2%). Positive results were observed on Berstein’s test for 68 patients (56.2%); 59 (86.8%) of them had non-erosive reflux disease. On the esophageal manometry, 35 (28.9%) of these patients had motility disorders. Nutcracker esophagus was observed in 27 patients (22.3%), nonspecific esophageal motility disorder was observed in 5 (4.1%), and hypertensive lower esophageal sphincter was observed in 3 (2.5%). Among the 52 patients with positive cardiac stress testing and a negative coronary angiogram (this clinically corresponded to microvascular angina), 46 patients (85.1%) showed abnormal findings on the gastro-esophageal studies. Conclusions : In our study, 85.1% of the patients with microvascular angina revealed positive results of gastric or esophageal disease. In spite of any existing evidence of microvascular angina or cardiac syndrome X, it would be more advisable to perform gastro-esophageal studies to adequately manage chest pain.

종설 : 관상동맥 질환에서 압력철선의 유용성

남창욱 ( Chang Wook Nam ) 대한내과학회 2011 대한내과학회지 Vol.81 No.6

To get the best clinical outcome after revascularization, understanding of patient and lesion should proceed. Although coronary angiography has been regarded as the gold standard for assessing coronary artery disease for several decades, it has several well-known limitations. Fractional flow reserve (FFR), measured with a coronary pressure wire, is an accurate and lesion-specific index for determining the functional significance (myocardial ischemia) of a particular stenosis. The selection of target vessels, the decision and method for revascularization, and the determination of prognosis in patients with CAD can be helped by FFR in daily practice. In this manuscript, we will review the role of pressure wire and discuss the limitation of it in evaluating CAD. (Korean J Med 2011;81:708-715)

Clinical Outcomes in Patients with Deferred Coronary Lesions according to Disease Severity Assessed by Fractional Flow Reserve

원기범,남창욱,조윤경,윤혁준,박형섭,김형섭,한성욱,허승호,김윤년,박상현,한정규,구본권,김효수,도준형,이성윤,양형모,임홍석,윤명호,탁승제,김권배 대한의학회 2016 Journal of Korean medical science Vol.31 No.12

Data on the clinical outcomes in deferred coronary lesions according to functional severity have been limited. This study evaluated the clinical outcomes of deferred lesions according to fractional flow reserve (FFR) grade using Korean FFR registry data. Among 1,294 patients and 1,628 lesions in Korean FFR registry, 665 patients with 781 deferred lesions were included in this study. All participants were consecutively categorized into 4 groups according to FFR; group 1: ≥ 0.96 (n = 56), group 2: 0.86–0.95 (n = 330), group 3: 0.81–0.85 (n = 170), and group 4: ≤ 0.80 (n = 99). Primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and target vessel revascularization. The median follow-up period was 2.1 years. During follow-up, the incidence of MACE in groups 1–4 was 1.8%, 7.6%, 8.8%, and 13.1%, respectively. Compared to group 1, the cumulative rate by Kaplan-Meier analysis of MACE was not different for groups 2 and 3. However, group 4 had higher cumulative rate of MACE compared to group 1 (log-rank P = 0.013). In the multivariate Cox hazard models, only FFR (hazard ratio [HR], 0.95; P = 0.005) was independently associated with MACE among all participants. In contrast, previous history of percutaneous coronary intervention (HR, 2.37; P = 0.023) and diagnosis of acute coronary syndrome (ACS) (HR, 2.35; P = 0.015), but not FFR, were independent predictors for MACE in subjects with non-ischemic (FFR ≥ 0.81) deferred coronary lesions. Compared to subjects with ischemic deferred lesions, clinical outcomes in subjects with non-ischemic deferred lesions according to functional severity are favorable. However, longer-term follow-up may be necessary.