This document provides biographical information about Dr. Wei-Chun Huang, including his academic and professional qualifications. It lists his positions, including serving as the director of the Department of Critical Care Medicine at Kaohsiung Veterans General Hospital, as well as his affiliations with professional organizations in Taiwan and internationally. The document also thanks the ICU departments from 14 hospitals across Taiwan for their participation in a conference.
Impact of statins and beta-blocker therapy on mortality after coronary artery...Paul Schoenhagen
Abstract
Background: We conducted a retrospective cohort study of patients after first-time isolated coronary artery bypass graft surgery (CABG) and assessed the impact of a discharge regimen including beta-blockers and statin therapy and their relationship to long-term all cause mortality and major adverse cardiovascular events (MACE).
Methods: We identified patients age >18 years, undergoing first time isolated CABG from 1993 to 2005. Patients were identified using the Cardiovascular Information Registry (CVIR). We collected follow-up information at 30, 60, 90 days and yearly follow-up. The registry is approved for use in research by the institutional review broad.
Results: We identified 5,205 patients who underwent single isolated CABG between January 1993 and December 2005. The mean age was 64.5±9.7 years and over 70% were male. There was a significant difference in the low density lipoproteins (LDL) concentration between those with or without statin medications (134±41.9 mg/dL) (no statin) vs. 126±44.8 mg/dL (with statin), P=0.001. A discharge regimen with statin therapy was associated with and overall reduction in 30 day, 1 year and long-term mortality. In addition, overall the triple ischemic endpoint of death, myocardial infarction (MI) and stroke was also significantly lower in the statin vs. no-statin group. In addition, statin and beta-blockers exerted synergistic effect on overall mortality outcomes short-term and in the long-term. We note that the predictors of overall death include no therapy with statin therapy and age [hazard ratios (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0, P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two groups starts to diverge immediately post discharge after single isolated CABG and continue to diverge through out the follow-up period.
Conclusions: A post-discharge regimen of statins independently reduces overall and 1 year mortality. These results confirm those of earlier studies within a contemporary surgical population and support the current clinical guidelines.
Impact of statins and beta-blocker therapy on mortality after coronary artery...Paul Schoenhagen
Abstract
Background: We conducted a retrospective cohort study of patients after first-time isolated coronary artery bypass graft surgery (CABG) and assessed the impact of a discharge regimen including beta-blockers and statin therapy and their relationship to long-term all cause mortality and major adverse cardiovascular events (MACE).
Methods: We identified patients age >18 years, undergoing first time isolated CABG from 1993 to 2005. Patients were identified using the Cardiovascular Information Registry (CVIR). We collected follow-up information at 30, 60, 90 days and yearly follow-up. The registry is approved for use in research by the institutional review broad.
Results: We identified 5,205 patients who underwent single isolated CABG between January 1993 and December 2005. The mean age was 64.5±9.7 years and over 70% were male. There was a significant difference in the low density lipoproteins (LDL) concentration between those with or without statin medications (134±41.9 mg/dL) (no statin) vs. 126±44.8 mg/dL (with statin), P=0.001. A discharge regimen with statin therapy was associated with and overall reduction in 30 day, 1 year and long-term mortality. In addition, overall the triple ischemic endpoint of death, myocardial infarction (MI) and stroke was also significantly lower in the statin vs. no-statin group. In addition, statin and beta-blockers exerted synergistic effect on overall mortality outcomes short-term and in the long-term. We note that the predictors of overall death include no therapy with statin therapy and age [hazard ratios (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0, P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two groups starts to diverge immediately post discharge after single isolated CABG and continue to diverge through out the follow-up period.
Conclusions: A post-discharge regimen of statins independently reduces overall and 1 year mortality. These results confirm those of earlier studies within a contemporary surgical population and support the current clinical guidelines.
http://www.theheart.org/web_slides/1283563.do
A study on Anglo-Scandinavian Cardiac Outcomes--Lipid Lowering Arm (ASCOT-LLA) designed to assess the effect on risk of normal MI and fatal CHD of two treatment strategies.
Goal attainments and their discrepancies for low density lipoprotein choleste...Paul Schoenhagen
Purpose: Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM.
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Jeremy Chow
Cardiologist, Electrophysiologist
Asian Heart & Vascular Centre
www.ahvc.com.sg
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
Dyslipidemia management an evidence based approachDr Vivek Baliga
How is dyslipidemia managed in clinical practice? Here is a short review on how current guidelines are shaping clinical practice, and how saroglitazar is playing a role in it.
http://www.theheart.org/web_slides/1283563.do
A study on Anglo-Scandinavian Cardiac Outcomes--Lipid Lowering Arm (ASCOT-LLA) designed to assess the effect on risk of normal MI and fatal CHD of two treatment strategies.
Goal attainments and their discrepancies for low density lipoprotein choleste...Paul Schoenhagen
Purpose: Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM.
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Jeremy Chow
Cardiologist, Electrophysiologist
Asian Heart & Vascular Centre
www.ahvc.com.sg
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
Dyslipidemia management an evidence based approachDr Vivek Baliga
How is dyslipidemia managed in clinical practice? Here is a short review on how current guidelines are shaping clinical practice, and how saroglitazar is playing a role in it.
Presentations by Tawfiq Choudhury and Rocco Hadland from the second webinar of the Mastering Cholesterol webinar series on Thursday 11 May 2023, focusing on Statins.
Un nuevo horizonte en el tratamiento de las dislipemias
14/09/15 18:00h-19:30h Casa del Corazón (Madrid)
http://objetivoLDL.secardiologia.es
#objetivoLDL
Abordaje terapéutico de la dislipemia en el paciente con enfermedad renal crónica
Dr. Jesús Egido de los Ríos, Jefe Servicio Nefrología e Hipertensión Fundación Jiménez Díaz (Madrid)
Atorvastatin: Statins in CVD management. Is just lipid lowering enough Dr Vivek Baliga
When it comes to management of cardiovascular diseases, are achieving lipid lowering targets sufficient. Here Dr Vivek Baliga, Consultant Internal medicine discusses the additional benefits of statins in CVD in India.
Impact of statins and beta-blocker therapy on mortality after coronary artery...Paul Schoenhagen
Background: We conducted a retrospective cohort study of patients after first-time isolated coronary artery bypass graft surgery (CABG) and assessed the impact of a discharge regimen including beta-blockers and statin therapy and their relationship to long-term all cause mortality and major adverse cardiovascular events (MACE).
Methods: We identified patients age >18 years, undergoing first time isolated CABG from 1993 to 2005. Patients were identified using the Cardiovascular Information Registry (CVIR). We collected follow-up information at 30, 60, 90 days and yearly follow-up. The registry is approved for use in research by the institutional review broad.
Results: We identified 5,205 patients who underwent single isolated CABG between January 1993 and December 2005. The mean age was 64.5±9.7 years and over 70% were male. There was a significant difference in the low density lipoproteins (LDL) concentration between those with or without statin medications (134±41.9 mg/dL) (no statin) vs. 126±44.8 mg/dL (with statin), P=0.001. A discharge regimen with statin therapy was associated with and overall reduction in 30 day, 1 year and long-term mortality. In addition, overall the triple ischemic endpoint of death, myocardial infarction (MI) and stroke was also significantly lower in the statin vs. no-statin group. In addition, statin and beta-blockers exerted synergistic effect on overall mortality outcomes short-term and in the long-term. We note that the predictors of overall death include no therapy with statin therapy and age [hazard ratios (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0, P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two groups starts to diverge immediately post discharge after single isolated CABG and continue to diverge through out the follow-up period.
Conclusions: A post-discharge regimen of statins independently reduces overall and 1 year mortality. These results confirm those of earlier studies within a contemporary surgical population and support the current clinical guidelines.
Instability and rupture of atherosclerotic plaques result in acute coronary syndrome.
LDL-C is usually related to ASCVD.
Statin medications are first-line therapy for LDL-C lowering Post ACS.
Rosuvastatin 20mg and 40 mg significantly increase HDL-C levels compared with Atorvastatin 80 mg
Dyslipidemia and CVS by Mohit Soni and Chandan KumarOlgaGoryacheva4
My students Mohit Soni and Chandan Kumar had presented this topic in our 22nd Student Scientific Society Conference in the department of Propaedeutic of Internal Diseases No.2
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
3. 黃偉春部長 Dr. Wei-Chun Huang,
MD, PhD, FESC, FACC, FHQS
• 美國心臟學院院士 FACC
• 歐洲心臟學會院士 FESC
• Stent Save a Life, Champion of TAIWAN
• 國際健康照護品質協會 ISQUa 品質專家 FHQS
• 亞洲緊急心導管治療大會APAC 主席團Course Director
• APAC Handbook of Primary PCI 編輯會議 編輯委員
• 美國心臟學會ACC 心臟衰竭教育計畫編輯委員
• 亞洲復甦醫學聯合會 RCA冠心病 Task Force委員
4. Prevalence of Hyperlipidemia in Taiwan Based on
Various PopulationsAuthor,
year Study period
Study design and
participants Definition Men (%) Women (%)
Pan and
Chiang,
1995
1991-1993
Ju-Dung, n= 77,789, age ≥35
y
Total cholesterol ≥240 mg/dL 9-13 7-18
1991-1993 Pu-Tzu, n= 45,018, age ≥35 y Total cholesterol ≥240 mg/dL 7-18 5-17
1990 National survey, age 35-64 y Triglycerides ≥200 mg/dL 12.0 7.0
Chang et al,
2002 2002
National survey, n= 5643, age
≥45 y
Total cholesterol ≥240 mg/dL or on medication 12.6 24.4
Triglycerides ≥200 mg/dL or on medication 12.3 11.9
LDL-C ≥160 mg/dL 14.8 17.2
HDL-C <35 mg/dL 14.4 9.5
Chien et al,
2005
1990-1991
Chin-Shan, n= 3605, age ≥35
y
Total cholesterol ≥240 mg/dL 14.1 19.8
Triglycerides ≥200 mg/dL or on medication 14.4 12.0
HDL-C <40 mg/dL 26.5 27.0
LDL-C ≥160 mg/dL 24.7 31.5
Pan et al,
2011
1993-1996 National survey, age ≥19 y Total cholesterol ≥240 mg/dL 10.2 11.2
2005-2008 Total cholesterol ≥240 mg/dL 12.5 10.0
1993-1996 Triglycerides ≥200 mg/dL 13.4 6.1
2005-2008 Triglycerides ≥200 mg/dL 20.8 7.9
Journal of the Formosan Medical Association (2017) 116, 217-248
7. 2017 Taiwan Lipid Guidelines for High Risk Patients
7
Disease LDL-C target
Primary target
ACS LDL-C < 70 mg/dL
ACS + DM LDL-C < 55 mg/dL can be considered
Stable CAD LDL-C < 70 mg/dL
Secondary target
ACS/CAD
TG > 200 mg/dL
Non HDL-C <100 mg/dL
J Formos Med Assoc. 2017 Apr;116(4):217-248.
8. Cardiovascular disease is a global crisis
• 50% of the world’s CVD burden is estimated to occur in
Asia1
• More than 26,000 people die from CVD each day in
Asia, that is 1 death every 4 seconds2
• Cardiovascular diseases (CVD) are the world’s leading
killer, which responsible for every third death3
8
Ohira T, Iso H. Cardiovascular disease epidemiology in Asia: an overview. Circ J. 2013;77:1646-52
Roth GA, Johnson C, Abajobir A, et al. Global, Regional, and National Burden of Cardiovascular Diseases
for 10 Causes, 1990-2015. J Am Coll Cardiol. 2017;70:1-25
World Health Organization. Cardiovascular disease fact sheet. Available from:
https://www.who.int/cardiovascular_diseases/en/ [Accessed on 13 Mar 2019]
9. MI and stroke survivors face a high risk of recurrent
events, particularly within the first year after an event
9FT Chiang, et al. JFMA.2014;113:794-802
M Lee, et al. Journal of Stroke 2016;18(1):60-65
Jernberg T, et al. Eur Heart J. 2015;36:1163-70
10. LDL-C reduction has a substantial impact on MI risk
• Uncontrolled LDL-C leaves these patients at risk of disease
progression and recurrent events
10MI=Myocardial infarction
Yusuf S, et al. Lancet. 2004;364:937-52.
11. N=591
Efficacy of High Intensity1 vs Moderate Intensity2 Atorvastatin for ACS
Patients with Diabetes Mellitus
Int J Cardiol. 2016 Nov 1; 222: 22-26.
LDL-C, mmol/L 3.2 ± 0.9 3.1 ± 0.7
High intensity
3 months
LDL-C, mmol/L 1.6 ± 0.5# 1.5 ± 0.5#
1.6 ± 0.6#1.9 ± 0.9 1.8 ± 0.7 1.8 ± 0.6
1High intensity statin: atorvastatin 40mg
2Moderate intensity statin: atorvastatin 20mg
123 119
61 73
12. N=591
Efficacy of High Intensity1 vs Moderate Intensity2 Atorvastatin for ACS
Patients with Diabetes Mellitus
Int J Cardiol. 2016 Nov 1; 222: 22-26.
MACE
(%)
Follow-up months
MACE, n (%)
Spontaneous MI, n (%)
Stroke, n (%)
One-year outcome of the two group
MACE, major adverse coronary events; MI, myocardial
infarction
High intensity
25 (8.4)
8 (2.7)
10 (3.4)
0.02
0.04
0.05
HR [95% CI] 0.61 [0.36 to 0.91], p = 0.026
1High intensity statin: atorvastatin 40mg
2Moderate intensity statin: atorvastatin 20mg
123 119
61
73
13. The Effect of Intensified Low Density Lipoprotein Cholesterol Reduction
on Recurrent Myocardial Infarction and Cardiovascular Mortality.
14. The Effect of Intensified Low Density Lipoprotein Cholesterol Reduction
on Recurrent Myocardial Infarction and Cardiovascular Mortality.
Acta Cardiol Sin. 2013 Sep;29(5):404-12.
17. 1.1.4 6–12 months of intensive statin
therapy
1.1.5 6–12 months of low-dose statin
therapy
The Effect of Statin Therapy on Plaque Regression following
Acute Coronary Syndrome
Coronary Artery Disease 2016, 27:636–649
Duration and doses of statins on plaque volumes N=162
3
18. 2.1.3 >6 months of intensive statin therapy and LDL-C ≤70
mg/dl
2.1.4 >6 months of intensive statin therapy and LDL-C >70
mg/dl
2.1.5 >6 months of low-dose statin therapy and LDL-C >70
mg/dl
Coronary Artery Disease 2016, 27:636–649
The Effect of Statin Therapy on Plaque Regression following Acute Coronary Syndrome
Duration and doses of statins, follow-up LDL-C levels on plaque volumes
N=162
3
19. Effects of Statin Intensity and Adherence on the
Long-Term Prognosis after Acute Ischemic Stroke
Event-free
survival1
Event-free
survival1
Year from index stroke Year from index stroke
Good adherence,
high event-free survival
High intensity statin,
high event-free survival
good adherence, high-
intensity
0.58 0.0270.36–0.94
Hazard ratios for primary outcomes by use of statin over a period of 6 months after acute ischemic stroke
N=8001
Stroke. 2017;48:2723-2730.
21. FDA – Relative LDL –lowering efficacy
http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm#aihp
22. 黃偉春部長 Dr. Wei-Chun Huang,
MD, PhD, FESC, FACC, FHQS
• 美國心臟學院院士 FACC
• 歐洲心臟學會院士 FESC
• Stent Save a Life, Champion of TAIWAN
• 國際健康照護品質協會 ISQUa 品質專家 FHQS
• 亞洲緊急心導管治療大會APAC 主席團Course Director
• APAC Handbook of Primary PCI 編輯會議 編輯委員
• 美國心臟學會ACC 心臟衰竭教育計畫編輯委員
• 亞洲復甦醫學聯合會 RCA冠心病 Task Force委員
23. Clinical Outcome of Statin plus Ezetimibe vs High-intensity Statin
Therapy in Patients with Acute Myocardial Infarction
Int J Cardiol. 2016 Dec 15; 225: 50-59.
High-intensity statin therapy was defined as atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg daily
Changes in the mean LDL levels
70.8 ± 29.28High-intensity statin
12-Months follow-
up
41.9 <0.01
N=3520
24. IMPROVE-IT:
Ezetimibe + Statin Improved CV Outcomes Beyond a Statin Alone
Primary End Point
CV death, nonfatal MI, hospital admission
for UA, coronary revascularization (≥30
days after randomization), or nonfatal
stroke
6.4%
RRR
HR, 0.936 (95% CI, 0.89–0.99)
P=0.016
Simvastatin 40 mga
(n=9,077)
2 3 4 5 6
Years Since Randomization
40
30
20
10
0
0 1 7
Ezetimibe/simvastatin 10/40 mgb
(n=9,067)
EventRate,
%
34.7
32.7
Cannon CP et al. N Engl J Med. 2015;372:2387–2397.
Ezetimibe/simvastatin significantly reduced CV events more than simvastatin alone
25. During the 34 months follow-up period, the risk of
recurrent IS:
SIM group was higher than that of the ATOR (HR,
2.03; 95% CI, 1.46 –2.82) and EZ-SIM (HR, 1.69;
95% CI, 1.14 –2.50) groups.
The risk of recurrent IS was not significantly lower in
the EZ-SIM compared to the ATOR group (HR, 1.20;
95% CI, 0.85–1.69).
Both high intensity statin and Ezetimibe-Simvastatin Therapy Reduce
Recurrent Ischemic Stroke Risks in Type 2 Diabetic Patients
Oneminussurvivalof
ischemicstroke
Days of follow up
SIM: 20 mg simvastatin
EZ-SIM: 10 mg ezetimibe –20 mg simvastatin
ATOR: 40 mg atorvastatin
J Clin Endocrinol Metab. 2016 Aug; 101(8): 2994-3001.
N=241
1
27. 感謝世界27國重症專家走進高榮
波蘭Poland Medical University of Silesia
西里西亞醫科大學
巴拉圭Paraguay
聖文森St. Vincent
拉脫維亞Latvia
印度India
Pune KEM hospital Gadkari教授
馬來西亞 Malaysia University
日本Japan National Cerebral and
Cardiovascular Center Yasuda教授
日本Japan International University of
Health and Welfare Mita Hospital Tamura教
授
烏拉圭Uruguay
日本東京大學
Japan Tokyo University Hatano教授
日本Japan Okayama Medical Center
Hiromi Matsubara 松原廣己教授
英國UK
倫敦帝國學院Imperial College London
越南Vietnam
首德醫院Thu Duc District Hospital 緬甸Myanmar
德國German University Giessen吉森大學
Ralph Schermuly 教授 Hossein A. Ghofranir教授
英國UK 劍橋大學
Cambridge University Deepa Gopalan教
授
馬來西亞Malaysia Universiti Putra
Malaysia Dr Foo Yoke Loong教授
中國China
深圳市孫逸仙心血管醫院 劉強教授中國China 廈門醫院 萬教授
韓國Korea
延世大学Yonsei University Jaewon Oh 教
授
美國 加州大學
UC San Diego Morris教授
新加坡Singapore陳篤生醫院
Tan Tock Seng Hospital Chia Yew Woon 教授
瓜地馬拉Guatemala
新加坡Singapore
黃廷芳綜合醫院 Ng Teng Fong
Hospital
中國China 蘇州明碁醫院
Suzhou BENQ Hospital
中國China 泉州第一醫院
Quanzhou First Hospital李德隆醫師/陳桂香護理長
中國China
南京明碁醫院Naijung BENQ Hospital
史瓦帝尼 Kingdom of Eswatini
尼加拉瓜Nicaragua
聖克里斯多福 St. Christopher
中國China 中日友好醫院
China-Japan Friendship Hospital 李晨 教授
加拿大Canada
新加坡Singapore 新加坡中央醫院
Singapore General Hospital Ng Shin Yi教授
韓國Korea
韓國大學Korea University Soon Jun Hong教
授
韓國Korea
Severance Cardiovascular Hospital Kang 教授
韓國Korea
亞洲大學Ajou University Chae Minjung Kathy教
授
高雄榮總KSVGH
重症醫學部
澳洲Australia 阿德萊德大學
Adelaide University Susanna Margaret
教授
澳洲Australia 蒙納士大學
Monash University David Pilcher教授
澳洲Australia
重症資料庫 ANZICS CORE主席
韓國Korea Samsung Medical Center
Sung- A Chang教授
埃及教授
Yasser Nassef 教授
蒙古專家
Byambatsogt Lkagvasuren醫師
菲律賓St. Luke's Medical Center
Andre Lawrence G. Tojino 醫師
印尼Universitas indonesia
Cardiovascular Hospital Harapan Kita
Nanda Iryuza醫師
希臘Nanjing University/ Emory Healthcare
Bill D. Gogas醫師
29. Loss-of-function Variants in PCSK9, with Lifetime Low
LDL-C, Are Associated With A Lower Risk of CV Events
29
Plasma LDL-C in black subjects
(mg/dL)
PCSK9 nonsense mutation
CHDSerum
LDL-C
Genetic
PCSK9
LDLR
No PCSK9 nonsense mutation (n=3278)PCSK9 nonsense mutation (n=85)
In frequency disribution of plasma LDL-C levels, green represents overlap in frequency of patients with and without PCSK9 mutations.
CHD = coronary heart disease; CV = cardiovascular; LDL-C = low-density lipoprotein cholesterol;
LDL-R = low-density lipoprotein receptor; PCSK9 = proprotein convertase subtilisin–kexin type 9.
Cohen JC, et al. N Engl J Med. 2006;354;1264-1272.
Frequency(%)
YesNo
88%
P=0.00812
8
4
CHD(%)
0
30
20
10
0
50 100 300150 200 250
50th percentile
30. Sever P & Mackay J. Br J Cardiol 2014;21:91-3
Giugliano RP, et al. Lancet 2012;380:2007-17
Sabatine MS, et al. NEJM 2015;372:1500-9
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
– Chaperones LDL-R to destruction → ↑ circulating LDL-C
– Loss-of-fxn genetic variants → ↑ LDL-R → ↓ LDL-C & ↓ risk of MI
Evolocumab
– Fully human anti-PCSK9
mAb
– Up to 77% ↓ LDL-C
– Safe & well-tolerated in Ph
2 & 3 studies
– Exploratory data
suggested ↓ CV events
How does PCSK9 inhibitor work?
evolocumab
30
31. FOURIER Trial to evaluate Evolocumab
and clinical outcomes
31
Objectives:
• Test whether the addition of evolocumab reduces the
incidence of major cardiovascular events
• Examine the long-term safety & tolerability of
evolocumab
• Investigate the efficacy and safety of achieving
unprecedented low levels of LDL-C
32. FOURIER Trial Design
Evolocumab SC
140 mg Q2W or 420 mg QM
Placebo SC
Q2W or QM
RANDOMIZED
DOUBLE BLIND
32
27,564 patients aged 40–85 years
Fasting LDL-C ≥ 70 mg/dL or non–HDL-C ≥ 100 mg/dL
after > 2 weeks of optimized stable lipid-lowering therapy*
Clinically evident CV disease
• History of myocardial infarction
• Nonhemorrhagic stroke
• Symptomatic peripheral artery disease
Plus additional risk factors
Follow-up Q 12 weeks; Median f/up 2.2 yrs
34. Baseline Demographics
34
Characteristics
Evolocumab
(N = 13,784)
Placebo
(N = 13,780)
Demographics
Age – y (SD) 62.5 (9.1) 62.5 (8.9)
Male sex – n (%) 10,397 (75.4) 10,398 (75.5)
White race* – n (%) 11,748 (85.2) 11,710 (85.0)
Weight – kg (SD) 85.0 (17.3) 85.5 (17.4)
Region
North America 2,287 (16.6) 2,284 (16.6)
Europe 8,666 (62.9) 8,669 (62.9)
Latin America 913 (6.6) 910 (6.6)
Asia Pacific and South Africa 1,918 (13.9) 1,917 (13.9)
*Race was self-reported. There were no nominally statistically significant differences in baseline
characteristics between the two arms except for weight (P=0.014).
Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
35. Baseline CV Risk Factors
35
*Race was self-reported. There were no nominally statistically significant differences in baseline
characteristics between the two arms except for weight (P=0.014).
Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
Characteristics
Evolocumab
(N = 13,784)
Placebo
(N = 13,780)
Type of atherosclerosis* – n (%)
Myocardial infarction 11,145 (80.9) 11,206 (81.3)
Non-hemorrhagic stroke 2,686 (19.5) 2,651 (19.2)
Peripheral artery disease 1,858 (13.5) 1,784 (12.9)
Cardiovascular risk factors
Hypertension – n/total n (%) 11,045/13,784 (80.1) 11,039/13,779 (80.1)
Diabetes mellitus – n (%) 5,054 (36.7) 5,027 (36.5)
Current cigarette use – n/total n (%) 3,854/13,783 (28.0) 3,923/13,779 (28.5)
36. Baseline Lipid-Lowering Therapies
and Lipid Parameters
36
*Statin intensity was categorized per the ACC/AHA Guidelines. Note, that in some countries where FOURIER was conducted, higher statin doses
are not approved. HDL, high-density lipoprotein; LDL, low-density lipoprotein; Lp(a) = Lipoprotein(a); IQR = Inter-quartile range
Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
Malinowski HJ, et all. J Clin Pharmacol. 2008;48:900-908
Characteristics
Evolocumab
(N = 13,784)
Placebo
(N = 13,780)
Statin use* – n (%)
High intensity 9,585 (69.5) 9,518 (69.1)
Moderate intensity 4,161 (30.2) 4,231 (30.7)
Low intensity, unknown intensity, or no data 38 (0.3) 31 (0.2)
Ezetimibe – n (%) 726 (5.3) 714 (5.2)
Other cardiovascular medications – n/total n (%)
Aspirin and/or P2Y12 inhibitor 12,766/13,772 (92.7) 12,666/13,767 (92.0)
Beta-blocker 10,441/13,772 (75.8) 10,374/13,767 (75.4)
ACE inhibitor or ARB and/or aldosterone antagonist 10,803/13,772 (78.4) 10,730/13,767 (77.9)
Lipid measures - Median (IQR) – mg/dL
LDL cholesterol – mg/dL 92 (80, 109) 92 (80, 109)
Total cholesterol – mg/dL 168 (151, 188) 168 (151, 189)
HDL cholesterol – mg/dL 44 (37, 53) 44 (37, 53)
Triglycerides – mg/dL 134 (101, 183) 133 (99, 181)
Lp(a) - nmol/L 37 (13, 166) 37 (13, 164)
37. Significant LDL-C Reduction by 59%
37
Placebo
Median 92 mg/dL
Evolocumab
Median 30 mg/dL
13,251 13,151 12,954 12,596 12,311 10,812 6,926 3,352 79013,779Placebo
13,288 13,144 12,964 12,645 12,359 10,902 6,958 3,323 76813,784Evolocumab
No. at risk
4
0
10
20
30
40
50
60
70
80
90
100
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168
Weeks
59% mean reduction (95%CI 58-60), P < 0.001
Absolute reduction: 56 mg/dL (95% CI 55-57)
LDLCholesterol(mg/dL)
Data shown are median values with 95% confidence intervals in the two arms; ITT.
Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
LDL-C was significantly reduced in the evolocumab group (median: 30 mg/dL)
including 42% who achieved levels ≤ 25 mg/dL vs < 0.1% in the placebo group
38. Add on Evolocumab Further Reduce
Cardiovascular Event Risk
38
6.0
10.7
14.6
5.3
9.1
12.6
No. at RiskPlacebo 13,780 13,278 12,825 1,871 7,610 3,690 686
Evolocumab 13,784 13,351 12,939 12,070 7,771 3,746 689
CumulativeIncidence(%)
Placebo
Evolocumab
0
2
4
6
8
10
12
14
16
0 6 1812 24 3630
Months
3.7
6.8
9.9
No. at RiskPlacebo
Evolocumab
CumulativeIncidence(%)
Placebo
Evolocumab
Months
0
2
4
6
8
9
10
11
0 6 1812 24 3630
1
3
5
7
13,780 13,449 13,142 12,288 7,944 3,893 731
13,784 13,501 13,241 12,456 8,094 3,935 724
3.1
5.5
7.9
CV = Cardiovascular; MI = Myocardial infarction; HR = Hazard ratio
Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
Key Secondary Endpoint:
Composite of CV Death, MI, or Stroke
Primary Endpoint:
Composite of CV Death, MI, Stroke, Hospitalization for UA, or
Coronary Revascularization
Hazard ratio 0.85
(95% CI 0.79 to 0.92);
P < 0.001
Hazard ratio 0.80
(95% CI 0.73 to 0.88);
P < 0.001
15% 20%
39. Primary endpoint was driven by reduction of
MI, stroke, and coronary revascularization
39
Outcome
Evolocumab
(n = 13,784)
n (%)
Placebo
(n = 13,780)
n (%)
HR
(95% CI)
P-
value‡
Primary endpoint* 1,344 (9.8) 1,563 (11.3) 0.85 (0.79-0.92) <0.001
Key secondary endpoint† 816 (5.9) 1,013 (7.4) 0.80 (0.73-0.88) <0.001
Other endpoints
CV death 251 (1.8) 240 (1.7) 1.05 (0.88-1.25) 0.62
Death from any cause 444 (3.2) 426 (3.1) 1.04 (0.91-1.19) 0.54
MI 468 (3.4) 639 (4.6) 0.73 (0.65-0.82) <0.001
Hospitalization for UA 236 (1.7) 239 (1.7) 0.99 (0.82-1.18) 0.89
Stroke 207 (1.5) 262 (1.9) 0.79 (0.66-0.95) 0.01
Coronary revascularization 759 (5.5) 965 (7.0) 0.78 (0.71-0.86) <0.001
CV Death or Hospitalization for
Worsening Heart Failure
402 (2.9) 408 (3.0) 0.98 (0.86-1.13) 0.82
Ischemic stroke or TIA 229 (1.7) 295 (2.1) 0.77 (0.65-0.92) 0.003
CTTC composite endpoint** 1,271 (9.2) 1,512 (11.0) 0.83 (0.77-0.90) <0.001
*Time to CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, whichever occurs first †CV death,
myocardial infarction, or stroke, whichever occurs first ‡Given the hierarchical nature of the statistical testing, the P values for the primary and key secondary
endpoint should be considered statistically significant, whereas all other P values should be considered nominal.
**CTTC stands for Cholesterol Treatment Trialists Collaboration and the composite endpoint consists of coronary heart death, nonfatal MI, stroke, or coronary
revascularization
MI = Myocardial infarction; UA = Unstable angina; TIA = Transient ischemic attack
40. The lowest is the best !
By achieved LDL-C Level
40
Giugliano RP, ESC Congress 2017, Barcelona 8/28/2017
LDL-C (mg/dL) Adj HR (95% CI)
<19 0.69 (0.56-0.85)
19-50 0.75 (0.64-0.86)
50-70 0.87 (0.73-1.04)
70-100 0.90 (0.78-1.04)
> 100 referent
P = 0.0001
CV Death, MI, or Stroke
越低
越好
LDL-C (mg/dL) at 4 weeks
19 58 7739 96 116 135 154 174
41. Longer duration of Evolocumab treatment
showed greater benefit over time
41
CV Death, MI, or Stroke
Year 1: RRR 16%
16%
13780 13617 13453 13291 13148
13784 13636 13505 13357 13248
Evolocumab
CumulativeIncidence(%)
0%
2%
4%
6%
8%
0 90 180 270 360DaysNo. at Risk
Placebo
Evolocumab
Placebo
Hazard ratio 0.84
(95% CI, 0.74-0.96)
> Year 1: RRR 25%
25%
13524 12609 8250 4056 925
13548 12721 8359 4051 911
0%
2%
4%
6%
8%
360 540 720 900 1080
CumulativeIncidence(%)
Days
Placebo
Evolocumab
Hazard ratio 0.75
(95% CI, 0.66-0.85)
Landmark analyses were performed in which patients who were alive and in follow-up at the start
of the period of interest formed the group at risk.
Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
(Supplementary Figure S4)
越久
越好
42. Larger benefit with Evolocumab observed
in higher-risk population
42
Subgroup N
3-Year KM Rate (%)
HR (95% CI ARR (95% CI) PintEvolocumab Placebo
All 22,351 8.0 9.9 0.82 (0.74, 0.91) 1.9 (0.7, 3.0)
Time of qualifying MI 0.18
<2 years 8402 7.9 10.8 0.76 (0.64, 0.89) 2.9 (1.2, 4.5)
≥ 2 years 13,918 8.3 9.3 0.87 (0.76, 0.99) 1.0 (-0.7, 2.7)
Number of prior MIs 0.57
≥ 2 5285 12.4 15.0 0.79 (0.67, 0.94) 2.6 (0.02, 5.3)
1 17,047 6.6 8.2 0.84 (0.74, 0.96) 1.7 (0.4, 2.9)
Residual Multivessel CAD 0.03
Present 5618 9.2 12.6 0.70 (0.58, 0.84) 3.4 (1.0, 5.9)
Absent 16,715 7.6 8.9 0.89 (0.79, 1.00) 1.3 (0.0, 2.6)
0.5 1.0 1.25
Favors evolocumab Favors placebo
CV Death, MI, or Stroke
Forest plot of the effect of evolocumab on the key secondary endpoint, overall (diamonds) and stratified by subgroups (squared depicting the point estimate and horizontal lines depicting 95%
confidence intervals). Kaplan-Meier event rate estimates, hazard ratios and absolute risk reductions with 95% confidence intervals are shown, as are the P values for interactions testing for the
hazard ratios.
Key secondary endpoint: composite of cardiovascular death, myocardial infarction, or stroke.
CAD = coronary artery disease; MI = myocardial infarction; CV = cardiovascular; HR = hazard ratio; CI = confidence interval; KM = Kaplan-Meier
Sabatine MS, et al. Circulation. [published online ahead of print April 6, 2018]. doi: 10.1161/CIRCULATIONAHA.118.034309.
Evolocumab reduced the key secondary endpoint by 24% (more recent MI),
21% (multiple prior MIs), and 30% (multivessel disease)
43. Greater risk reduction by Evolocumab in
patients with PAD
43
Bonaca MP, et al. Circ. 2017. [published online ahead of print November 13, 2017]. doi: 10.1161/CIRCULATIONAHA.117.032235.
PAD = Solid lines, n = 3,642; No PAD = Dotted lines, n= 23,922. HR (95% CI) are shown; 2.5 year KM rate.
Primary endpoint = composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularization.
Key secondary endpoint = composite of cardiovascular death, myocardial infarction, or stroke.
ARR = absolute risk reduction; HR = hazard ratio; NNT = number needed to treat; PAD = peripheral artery disease; RRR = relative risk reduction.
Patients with a history of PAD treated with evolocumab experienced a consistent RRR and
greater ARR for both the primary and secondary endpoints compared to those without a
history of PAD
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
0 180 360 540 720 900
Key Secondary Endpoint
Days from Randomization
13.0%
7.6%
9.5%
6.2%
PAD (N = 3,642)
HR: 0.73 (0.59 – 0.91)
P = 0.0040
No PAD (N = 23,922)
HR: 0.81 (0.73 – 0.90)
P < 0.001
PAD
3.5% ARR
NNT 29
No PAD
1.4% ARR
NNT 72
Pinteraction = 0.41
Primary Endpoint
Days from Randomization
RiskofEndpoint
16.8%
12.1%
13.3%
10.5%
No PAD
1.6% ARR
NNT 63
PAD (N = 3,642)
HR: 0.79 (0.66 – 0.94)
P = 0.0098
No PAD (N = 23,922)
HR: 0.86 (0.80 – 0.93)
P < 0.001
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
0 180 360 540 720 900
Pinteraction = 0.40
PAD
3.5% ARR
NNT 29
Evolocumab
Placebo
44. FOURIER
Further cardiovascular OUtcomes Research with
PCSK9 Inhibition in subjects with Elevated Risk:
Efficacy and Safety of Long-term Evolocumab Use
Among Asian Subjects
A Keech, P Sever, L Jiang, A Hirayama, C Lu, L Tay, P
Deedwania, C-W Siu, A Lira Pineda, D Choi, M-J Charng, J
Amerena, W Wan Ahmad, V Chopra, T Pedersen, R Giugliano, M
Sabatine on behalf of the FOURIER Study Group.
ACC Shanghai, December 2018
44
SC-TWN-AMG145-00117-1218
45. Characteristics Asian (N=2,723)
Others
(N=24,841)
Age (yrs) mean 61.4 62.6
Male sex 79.5% 75%
Weight (kg) - mean 70.6 86.9
Type of atherosclerosis
Myocardial infarction alone 67.5% 69.55
Non-hemorrhagic stroke alone 20.6% 11.3%
Peripheral artery disease alone 1.8% 5.9%
Hypertension 71.8% 81.0%
Diabetes mellitus 50.3% 35.1%
Current cigarette use 27.1% 28.3%
High intensity statin use 33.3% 73.3%
Median lipid measures
LDL cholesterol - mg/dl 89 92
Total cholesterol - mg/dl 161 168
HDL cholesterol - mg/dl 41.5 44.0
Triglycerides - mg/dl 126 134
Lipoprotein(a) - mg/dl 39 37
China
Japan
Philippines
South Korea
Taiwan
Malaysia
Hong Kong
Singapore
2215
Other Asian
508
Baseline Characteristics by Race
46. Similar Absolute Reduction in LDL-C with
Evolocumab Regardless of Race
Median
LDL-c
Asian
(2,723)
Others
(24,841)
Difference
Baseline 89 mg/dL 92 mg/dL
48 Weeks 22 mg/dL 30 mg/dL
Median
Change vs
Pbo
-66.5 mg/dL -61.0 mg/dL P<0.0001
46
52. No safety concerns with very low
LDL-C concentrations
52
0
5
10
15
20
25
SAE AE->Discon New DM Cancer Cataract
<0.5
0.5-1.3
1.3-1.8
1.8-2.6
LDL-C (mM) at 4wks
Giugliano RP. et al. Lancet 2017; 390: 1962–71
% pts
53. No safety concerns with very low
LDL-C concentrations
53
0
5
10
Neurocog AST/ALT↑ CK↑ Non-CV death Hem stroke
<0.5
0.5-1.3
1.3-1.8
1.8-2.6
LDL-C (mM) at 4wks
Giugliano RP. et al. Lancet 2017; 390: 1962–71
% pts
54. HbA1c and FPG levels over time remained similar
between the treatment groups in patients with or
without diabetes
54
HbA1c(%)
Weeks
No diabetes
4
5
6
7
8
9
10
0 24 48 72 96 120 144 168
70
80
90
100
110
120
130
140
150
160
170
180
0 24 48 72 96 120 144 168
HbA1c
FPG(mg/dL)
Evolocumab
Placebo
Weeks
FPG
FPG = Fasting plasma glucose
Data are median values in the evolocumab and placebo treatment groups, for patients with and without diabetes.
Error bars are IQRs.
Sabatine MS, et al. Lancet Diab Endocrinol. [published online ahead of print September 15, 2017]. doi: 10.1016/S2213-8587(17)30313-3.
Diabetes
56. Long-term Evolocumab for the
Treatment of Hypercholesterolemia
Michael J. Koren, MD; Marc S. Sabatine, MD, MPH; Robert P. Giugliano, MD, SM; Gisle
Langslet, MD, PhD; Stephen D. Wiviott, MD; Andrea Ruzza, MD, PhD, Yuhui Ma, PhD;
Andrew W. Hamer, MD; Scott M. Wasserman, MD; Frederick J. Raal, MBBCh, MMED,
PhD
Jacksonville Center for Clinical Research, Jacksonville, FL (MJK); Brigham and Women’s Hospital, Harvard
Medical School, Boston, MA (MSS, RPG, SDW); Lipid Clinic, Oslo University Hospital, Nydalen, Oslo, Norway
(GL); Amgen Inc., Thousand Oaks, CA (AR, YM, AWH, SMW); University of the Witwatersrand, Johannesburg,
South Africa (FJR)
FINAL REPORT OF THE OSLER-1 STUDY
November 12, 2018, George Lyman Duff Memorial Lecture
American Heart Association Scientific Sessions, Chicago, Illinois
57. Prevalence of Hyperlipidemia in Taiwan Based on
Various PopulationsAuthor,
year Study period
Study design and
participants Definition Men (%) Women (%)
Pan and
Chiang,
1995
1991-1993
Ju-Dung, n= 77,789, age ≥35
y
Total cholesterol ≥240 mg/dL 9-13 7-18
1991-1993 Pu-Tzu, n= 45,018, age ≥35 y Total cholesterol ≥240 mg/dL 7-18 5-17
1990 National survey, age 35-64 y Triglycerides ≥200 mg/dL 12.0 7.0
Chang et al,
2002 2002
National survey, n= 5643, age
≥45 y
Total cholesterol ≥240 mg/dL or on medication 12.6 24.4
Triglycerides ≥200 mg/dL or on medication 12.3 11.9
LDL-C ≥160 mg/dL 14.8 17.2
HDL-C <35 mg/dL 14.4 9.5
Chien et al,
2005
1990-1991
Chin-Shan, n= 3605, age ≥35
y
Total cholesterol ≥240 mg/dL 14.1 19.8
Triglycerides ≥200 mg/dL or on medication 14.4 12.0
HDL-C <40 mg/dL 26.5 27.0
LDL-C ≥160 mg/dL 24.7 31.5
Pan et al,
2011
1993-1996 National survey, age ≥19 y Total cholesterol ≥240 mg/dL 10.2 11.2
2005-2008 Total cholesterol ≥240 mg/dL 12.5 10.0
1993-1996 Triglycerides ≥200 mg/dL 13.4 6.1
2005-2008 Triglycerides ≥200 mg/dL 20.8 7.9
Journal of the Formosan Medical Association (2017) 116, 217-248
58. Prevalence of Hyperlipidemia in Taiwan Based on
Various PopulationsAuthor,
year Study period
Study design and
participants Definition Men (%) Women (%)
Pan and
Chiang,
1995
1991-1993
Ju-Dung, n= 77,789, age ≥35
y
Total cholesterol ≥240 mg/dL 9-13 7-18
1991-1993 Pu-Tzu, n= 45,018, age ≥35 y Total cholesterol ≥240 mg/dL 7-18 5-17
1990 National survey, age 35-64 y Triglycerides ≥200 mg/dL 12.0 7.0
Chang et al,
2002 2002
National survey, n= 5643, age
≥45 y
Total cholesterol ≥240 mg/dL or on medication 12.6 24.4
Triglycerides ≥200 mg/dL or on medication 12.3 11.9
LDL-C ≥160 mg/dL 14.8 17.2
HDL-C <35 mg/dL 14.4 9.5
Chien et al,
2005
1990-1991
Chin-Shan, n= 3605, age ≥35
y
Total cholesterol ≥240 mg/dL 14.1 19.8
Triglycerides ≥200 mg/dL or on medication 14.4 12.0
HDL-C <40 mg/dL 26.5 27.0
LDL-C ≥160 mg/dL 24.7 31.5
Pan et al,
2011
1993-1996 National survey, age ≥19 y Total cholesterol ≥240 mg/dL 10.2 11.2
2005-2008 Total cholesterol ≥240 mg/dL 12.5 10.0
1993-1996 Triglycerides ≥200 mg/dL 13.4 6.1
2005-2008 Triglycerides ≥200 mg/dL 20.8 7.9
Journal of the Formosan Medical Association (2017) 116, 217-248
59. At Year 5, mean (SE)/ median (IQR) percentage change in LDL-C from baseline:
Evolocumab plus SOC: –56% (1%)* / –59% (–71%, –44%)*
Parent SOC-controlled period
Baseline 12 24 36 52 64 76 88 100 112 124 136 148 160 172 184 196 208 220 232 244 260
OSLER-1 Study Period, wk
–100
–75
–50
–25
0
25
%ChangeFromBaseline
All-evolocumab period
4: EvoMab/EvoMab + SoC/EvoMab + SoC (N = 643)
2: Control/EvoMab + SoC/EvoMab + SoC (N = 239)
3: EvoMab/SoC/EvoMab + SoC (N = 322)
1: Control/SoC/EvoMab + SoC (N = 120)
Phase 2
parent
study
wk 12
*P<0.001 vs placebo
EvoMab, evolocumab; Wk, week
Results
OSLER-1: LDL-C % change from baseline
60. Summary
Year 2 Year 3 Year 4 Year 5
Persistent reductions in LDL-C over 5 years
56% 57% 56% 56%
LDL-C
Mean
% change
from
baseline
Consistent safety over 5 years treatment
• AEs stayed stable or tracked lower over the treatment course
• Discontinued evolocumab due to AEs: 1.4%/year
• 4 instances of transient binding antibodies (2 SOC, 2 evolocumab)
• No neutralizing antibodies detected over 5 years
61. Summary: Evolocumab significantly reduce major cardiovascular
events beyond statin therapy in established CVD
• ↓ CV outcomes in patients already on statin therapy
– 15% ↓ broad primary endpoint; 20% ↓ CV death, MI, or stroke
– Evolocumab reduced the key secondary endpoint by
• 24% (more recent MI)
• 21% (multiple prior MIs)
• 30% (multivessel disease)
– 25% reduction in CV death, MI, or stroke after 1st year
• Safe and well-tolerated
– Similar rates of AEs, incl DM & neurocog events w/ Evolocumab & pbo
– Rates of Evolocumab discontinuation low and no greater than pbo
– No neutralizing antibodies developed
61
71. National Taiwan University Hospital
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