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.

Effect of edaravone in diabetes mellitus-induced nephropathy in rats

Varatharajan, Rajavel,Lim, Li Xin,Tan, Kelly,Tay, Chai Sze,Teoh, Yi Leng,Akhtar, Shaikh Sohrab,Rupeshkumar, Mani,Chung, Ivy,Abdullah, Nor Azizan,Banik, Urmila,Dhanaraj, Sokkalingam A.,Balakumar, Pitch The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.4

Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i .p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a significant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i .p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.

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

( Chang-wook Nam ),( Dong-soo Kim ),( Jianyong Li ),( Marie T. Baccara-dinet ),( Ivy Li ),( Ji-hyun Kim ),( Chong-jin Kim ) 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.

A Survey of Osteoporosis and Breast Cancer Risk Perception among Menopausal and Postmenopausal Women in Hong Kong

( Louis Wc Chow ),( Michael Mc Cheung ),( Jennifer Wj Chu ),( Ivy Cf Li ) 대한폐경학회 2017 대한폐경학회지 Vol.23 No.2

Objectives: A lack of understanding in menopausal and postmenopausal women`s (PMW) risk perception towards osteoporosis and breast cancer still exists, which is explored in this study. This information might allow health professionals to conduct interventions to improve health behaviors before menopause-related diseases are imminent. Methods: Between 10 December 2015 and 31 January 2016, 573 menopausal or PMW were successfully interviewed on 17 questions, comprising separate sections for osteoporosis and breast cancer. The target respondents were menopausal or PMW aged 45 to 60 years, with no previous diagnosis of osteoporosis or breast cancer, who attended private clinics across Hong Kong for annual physical examination. Results: Regarding menopausal issues, the top three concerns were osteoporosis and fracture (72%), breast cancer (44%), and sleep disorder/insomnia/headache (40%). Among 314 respondents (55%) who tried to prevent osteoporosis, 74% of them began to do it after they were 40 years old. On the other hand, 65% of respondents never had a bone density test. For respondents who said “I`m too young, so I don`t need to check”, their mean age was 52 years old. Ninety percent of respondents mistakenly believed that regular breast examination, regular breast massage, drink soy milk, or vaccine can prevent breast cancer. Conclusions: This survey revealed osteoporosis and breast cancer as the top concerns among menopausal and PMW in Hong Kong. Inadequate health behaviors and misconceptions still exist despite widespread health education in the recent years. (J Menopausal Med 2017;23:102-107)