In the NOACs era , how to deal with liver cirrhosis needing anticoagulation?magdy elmasry
Is My Cirrhotic Patient Auto-anticoagulated?
Does "Auto-anticoagulation" Protect Against thrombosis in Patients with Liver Disease?
The normal balance of hemostasis and rebalanced hemostasis in liver disease.Should we anti-coagulate patients with cirrhosis?How safe is anticoagulation therapy to use in those with chronic liver disease?
In the NOACs era , how to deal with liver cirrhosis needing anticoagulation?magdy elmasry
Is My Cirrhotic Patient Auto-anticoagulated?
Does "Auto-anticoagulation" Protect Against thrombosis in Patients with Liver Disease?
The normal balance of hemostasis and rebalanced hemostasis in liver disease.Should we anti-coagulate patients with cirrhosis?How safe is anticoagulation therapy to use in those with chronic liver disease?
http://www.theheart.org/web_slides/1425587.do
A randomized to placebo or ivabradine study on Systolic Heart Failure Treatment with the If Inhibitor Ivabradine (SHIFT) with patients on standard HF medications according to guidelines
Atrial fibrillation (afib) is one of the main causes of strokes in the US. New treatment options are available - both medical therapy (such as new blood thinners) and procedures (watchman left atrial appendage closure).
- Describe the basic characteristics of new oral anticoagulants (OACs)
- Recognize potential candidates for new anticoagulants for atrial fibrillation and treatment of venous thrombosis
Dabigatran for Atrial Fibrillation: Cardioversion and Ablationlarriva
The presentation covers background information regarding atrial fibrillation (A-fib) and the use of oral anticoagulant dabigatran surrounding cardioversion and ablation for A-fib. The information surrounds a patient case in which the patient prefers dabigatran over warfarin. Available literature on the topic is analyzed to make a patient specific recommendation.
Journal Club evaluation, effect of Rivaroxaban in heart failure
background of heart failure, pathophysiology, epidemiology and the treatment algorithm.
Anticoagulation in CKD patients with AFد.محمود نجيب
chronic kidney disease is associated with increased risk of both thrombosis and bleeding, so in CKD patients with AF it is a challenging problem whether to be anticoagulated or not
Newer Oral Anticoagulants In Atrial Fibrillation - Dr Vivek BaligaDr Vivek Baliga
In this presentation, Dr Vivek Baliga, Baliga Diagnostics Bangalore, discusses the role of new oral anticoagulants in the management of non-valvular atrial fibrillation.
What are anti-coagulants?
What are the difference between antiplatelet, anticoagulants and thrombolytics?
Coagulation cascade
Virchows Triad
Classification of anti-coagulants?
Indications of anti-coagulants?
Mechanism and site of action of different anti-coagulants?
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
http://www.theheart.org/web_slides/1425587.do
A randomized to placebo or ivabradine study on Systolic Heart Failure Treatment with the If Inhibitor Ivabradine (SHIFT) with patients on standard HF medications according to guidelines
Atrial fibrillation (afib) is one of the main causes of strokes in the US. New treatment options are available - both medical therapy (such as new blood thinners) and procedures (watchman left atrial appendage closure).
- Describe the basic characteristics of new oral anticoagulants (OACs)
- Recognize potential candidates for new anticoagulants for atrial fibrillation and treatment of venous thrombosis
Dabigatran for Atrial Fibrillation: Cardioversion and Ablationlarriva
The presentation covers background information regarding atrial fibrillation (A-fib) and the use of oral anticoagulant dabigatran surrounding cardioversion and ablation for A-fib. The information surrounds a patient case in which the patient prefers dabigatran over warfarin. Available literature on the topic is analyzed to make a patient specific recommendation.
Journal Club evaluation, effect of Rivaroxaban in heart failure
background of heart failure, pathophysiology, epidemiology and the treatment algorithm.
Anticoagulation in CKD patients with AFد.محمود نجيب
chronic kidney disease is associated with increased risk of both thrombosis and bleeding, so in CKD patients with AF it is a challenging problem whether to be anticoagulated or not
Newer Oral Anticoagulants In Atrial Fibrillation - Dr Vivek BaligaDr Vivek Baliga
In this presentation, Dr Vivek Baliga, Baliga Diagnostics Bangalore, discusses the role of new oral anticoagulants in the management of non-valvular atrial fibrillation.
What are anti-coagulants?
What are the difference between antiplatelet, anticoagulants and thrombolytics?
Coagulation cascade
Virchows Triad
Classification of anti-coagulants?
Indications of anti-coagulants?
Mechanism and site of action of different anti-coagulants?
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Internal Medicine Board Review: Anticoagulation in atrial fibrillation - CHAD...Knowmedge
ABIM internal medicine exam review: Patients with atrial fibrillation should be stratified according to their risk of stroke so that they can be placed on the appropriate antithrombotic regimen. A simple clinical tool to perform this risk stratification is the CHADS2 score. A revised extension of the CHA2DS2-VASc score has been developed and has shown incremental improvement in the classification of a patient’s risk.
Huy Tran is a lab and clinical haematologist at Peninsula Health. He has research interests in haemostasis and thrombosis and is a member of the Australasian committee for anticoagulation reversal. Here he presents on the new oral anticoagulants and what can be done when they cause critical bleeding
Warfarin is an anticoagulant normally used in the prevention of thrombosis and thromboembolism, the formation of blood clots in the blood vessels and their migration elsewhere in the body, respectively.
WATCHMAN™ Left Atrial Appendage Closure Device is a first-of-its-kind, proven alternative to long-term warfarin therapy for stroke risk reduction in patients with non-valvular atrial fibrillation.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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!
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Evaluation of antidepressant activity of clitoris ternatea in animals
New Oral anticoagulants
1. An Updated Review of
Target-Specific Oral Anticoagulants Used in
Stroke Prevention in Atrial Fibrillation
Diya Saleh
Registrar, BPT
2. Question #1
An 82 year old man. What is the chance he has
atrial fibrillation?
A.
B.
C.
D.
1%
5%
10%
25%
3. Prevalence of Diagnosed AF
Stratified by Age and Sex
12.0
10.0
Women
Men
11.1
10.3
9.1
8.0
7.3
6.0
5.0
4.0
3.0
1.7
2.0
0.0
0.1 0.2 0.4
<55
0.9
7.2
5.0
x-axis = %
y-axis = # of
men/women
3.4
1.7
1.0
55-59
60-64
65-69
70-74
75-79
80-84
> 85
# Women
530
310
566
896
1498
1572
1291
1132
# Men
1529
634
934
1426
1907
1886
1374
759
Go AS, JAMA. 2001 May 9;285(18):2370-5. Pub Med PMID: 11343485
4. Question #2
A 46 year old. What is his lifetime risk of
developing AF?
A.
B.
C.
D.
1%
5%
10%
25%
5. Incidence of AF
Lifetime Risk for AF at Selected Index Ages by Sex
Index Age, yrs
Men
Women
40
26.0% (24.0 – 27.0)
23.0% (21.0 – 24.0)
50
25.9% (23.9 – 27.0)
23.2% (21.3 – 24.3)
60
25.8% (23.7 – 26.9)
23.4% (21.4 – 24.4)
70
24.3% (22.1 – 25.5)
23.0% (20.9 – 24.1)
80
22.7% (20.1 – 24.1)
21.6% (19.3 – 22.7)
1 in 4
Men & women
>40 Years
will develop AF
Lifetime risk if
currently free
of AF
Lloyd-Jones DM, et al. Circulation. 2004 Aug 31;110(9):1042-6. Pub Med PMID: 15313941.
6. Question #3
68 year old female with atrial fibrillation and no
other co-morbidities. How would you classify
her stroke risk?
A. Low
B. Moderate
C. High
7. CHA2DS2-VASc
2009 Birmingham Schema Expressed as a Point-Based Scoring System
Risk Factor
Congestive heart failure/LV dysfunction
Hypertension
Age ≥ 75 y
Diabetes mellitus
Stroke/TIA/TE
Vascular disease
(prior myocardial infarction, peripheral artery disease, or aortic plaque)
Age 65-74 y
Sex category
(i.e. female gender)
LV = left ventricular; TE = thromboembolism
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest. 2010 Feb;137(2):263-72. Pub Med PMID: 19762550.
Score
1
1
2
1
2
1
1
1
8. Question #3
68 year old female with atrial fibrillation and no
other co-morbidities. How would you classify
her stroke rate per year?
A.
B.
C.
D.
1%
2%
3%
4%
9.
10. Question #4
78 year old male with atrial fibrillation and
hypertension (CHADS2 score = 2 [4% stroke rate per
year]). What is his annual major bleeding rate?
A.
B.
C.
D.
E.
1%
2%
3%
5%
10%
12. Bleeding Risk Scores in AF
ATRIA
HAS-BLED
HEMORR2HAGES
Anemia1
3
Hypertension4
1
Hepatic10 or
disease2
1
1
Severe renal disease2
3
Abnormal Renal5 or
1
1
Ethanol abuse
1
Age ≥75 yrs
2
Stroke
1
Malignancy
1
Any prior hemorrhage
1
Bleeding
1
Older Age (>75 yrs)
1
Hypertension3
1
Labile INR8
1
Reduced platelet number
1
Elderly (>65 yrs)
1
Rebleeding12
2
Drugs9 or
1
1
Hypertension4
1
Anemia13
1
Genetic factors14
1
Excessive fall risk15
1
Stroke
1
1.
2.
3.
4.
5.
6.
8.
9.
10.
11.
12.
13.
14.
15.
Liver
function6
Hemoglobin <13 g/dl men; <12 g/dl women
Estimated glomerular filtration rate <30 ml/min or dialysis-dependent
Diagnosed hypertension
Systolic blood pressure >160 mmHg
Presence of chronic dialysis or renal transplantation or serum creatinine ≥200 mmol/L
Chronic hepatic disease (eg cirrhosis) or biochemical evidence of significant hepatic derangement (eg bilirubin 2 x upper limit of normal, in
association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3 x upper limit normal, etc.)
Unstable/high INRs or poor time in therapeutic range (eg <60%)
Concomitant use of drugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse etc.
Cirrhosis, two-fold or greater elevation of AST or APT, or albumin <3.6 g/dl
Platelets <75,000, use of antiplatelet therapy (eg daily aspirin) or NSAID therapy; or blood dyscrasia
Prior hospitalization for bleeding
Most recent hematocrit <30 or hemoglobin <10 g/dl
CYP2C9*2 and/or CYP2C9*3
Alzheimer's dementia, Parkinson's disease, schizophrenia, or any condition predisposing to repeated falls
Alcohol
Renal
or function11
Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. J Am Coll Cardiol 2012;60:000–000. 2012 Jul 24. [Epub ahead of print] Online Appendix.
PMID: 22858389.
13. Question #5
78 year old female with atrial fibrillation on
warfarin, hypertension and CHF.
How many times she needs to fall in a year for the
calculated risk of subdural hematoma from falling
to outweigh the stroke reduction benefit of
warfarin?
A.
B.
C.
D.
E.
10 times
30 times
100 times
300 times
600 times
14. Anticoagulation and Risk of Falls in the Elderly –
Putting Matters in Perspective
• The risk of a subdural hematoma from falling is so small.
• A patient with a 5% annual stroke risk from AF would
need to fall 300 times in a year for the calculated risk of
subdural hematoma from falling to outweigh the stroke
reduction benefit of warfarin.
•
•
Man-Son-Hing M, Laupacis A. Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians' fears often
unfounded. Arch Intern Med 2003; 163:1580.
Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation
who are at risk for falls. Arch Intern Med 1999; 159:677.
• Sellers MB, Newby LK. Atrial fibrillation, anticoagulation, fall risk, and
outcomes in elderly patients. Am Heart J 2011; 161:241.
18. Warfarin the underdog!
• Is NOT rat poison
– Rats have evolved (and so
should you…)
• Advantages of warfarin
– Active by the oral route
– Once daily dosing
– Can be monitored
•
•
•
•
Surgeries
Bleeding episodes
Recurrent events
Adherence
– Rapidly-acting antidote
available
– Low cost
19. Problems with Warfarin
•
Food and drug interactions
•
Genetic variation in metabolism
•
dosage adjustments &
freq. monitor with INR
narrow therapeutic window
overlap with parenteral drugs
•
slow onset of action
20. A Cardiologist’s Perspective:
On The Shifting Role of Warfarin
• Warfarin has important limitations that
contribute to underutilization and poor INR
control
– 3 of 4 patients with AF are unprotected or poorly
protected against stroke
• Warfarin will continue to play an important
role:
– For other indications (e.g., prosthetic valves)
– In patients with renal impairment (i.e., CrCl < 15
ml/min)
24. Why Bother To Innovate?
• It’s just too bad that
•
•
•
•
You wouldn’t necessarily get there on time
Comfort would be a significant problem
Forget about “hands free” anything
And who needs seat belts, automatic transmission,
parking/lane change/braking assist, etc., anyway?
25. Why Bother To Innovate?
Safety and convenience are overrated and not worth the money;
you’ll still get from point A to point B… Maybe...
• If you are unlucky enough to crash you will probably survive
• And while you are unlikely ever to be able to replace any broken
parts, well… just get someone else to drive you the next time
26. AN “IDEAL” ANTI COAGULANT
•
•
•
•
•
„Fixed‟ „oral‟ dose
No need for dose adjustment
Wide therapeutic range
Acceptable bleeding risks
No need for monitoring
29. Potential Limitations of New
Anticoagulants
• Antidotes
– None of the newer agents has a specific antidote
•
•
•
•
•
•
Monitoring
Adverse Drug Events
Compliance
Cost
Clinical Trials vs. Actual Clinical Practice
Patient populations not even studied (i.e. Cancer)
30. No blood monitoring is an advantage of
NOACs
but it is also a major disadvantage…
33. Primary Endpoints
Atrial Fibrillation Trials
Study
NOAC
VKA
Outcome
RE-LY
Dabigatran
1.1%
Warfarin
1.7%
RR 0.66
95% CI 0.53-0.82
P < 0.001
superiority
ARISTOTLE
Apixaban
1.3%
Warfarin
1.6%
HR 0.79
95% CI 0.66-0.95
P= < 0.001 Non- I
P= 0.01
Superiority
ROCKET-AF
Rivaroxaban
1.7%
Warfarin
2.2%
HR 0.79
95% CI 0.66-0.96
P = <0.001
Non-Inferiority
34. Major Bleeding
Atrial Fibrillation Trials
Study
NOAC
VKA
Outcome
RE-LY
Dabigatran
3.3%
Warfarin
3.6%
RR 0.93
95% CI 0.81-1.07
P = 0.31
ARISTOTLE
Apixaban
2.1%
Warfarin
3.1%
HR 0.69
95% CI 0.60-0.8
P = < 0.001
ROCKET-AF
Rivaroxaban
5.6%
Warfarin
5.4%
HR 1.04
95% CI 0.90-1.20
P = 0.58
35. Intracranial Hemorrhage
Atrial Fibrillation Trials
Study
NOAC
VKA
Outcome
RE-LY
Dabigatran
0.3%
Warfarin
0.7%
RR 0.40
95% CI 0.27-0.60
P= <0.001
ARISTOTLE
Apixaban
0.3%
Warfarin
0.8%
HR 0.42
95% CI 0.30-0.58
P = <0.001
ROCKET-AF
Rivaroxaban
0.5%
Warfarin
0.7%
HR 0.67
95% CI 0.47-0.93
P = 0.02
36.
37.
38.
39.
40.
41.
42.
43.
44.
45. Meta-analysis of Efficacy and Safety of
New Oral Anticoagulants
Dabigatran, Rivaroxaban, Apixaban vs. Warfarin in AF patients
All cause stroke/SEE
Ischemic and unspecified stroke
Hemorrhagic stroke
Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Am J Cardiol. 2012 Aug 1;110(3):453-60. Pub Med PMID: 22537354..
46. Meta-analysis of Efficacy and Safety of
New Oral Anticoagulants
Dabigatran, Rivaroxaban, Apixaban vs. Warfarin in AF patients
Major bleeding
Intracranial bleeding
GI Bleeding
Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Am J Cardiol. 2012 Aug 1;110(3):453-60. Pub Med PMID: 22537354.
47. Reversal of NOACs
Suggestions for Reversal of New Oral Anticoagulants
Apixaban
Dabigatran
Rivaroxaban
Oral activated charcoal
Yes
Yes
Yes
Hemodialysis
No
Yes
No
Hemoperfusion with
activated charcoal
Possible
Yes
Possible
Fresh frozen plasma
No
No
No
Activated factor VIIa
Unclear
Unclear
Unclear
3-factor PCC
Unclear
Unclear
Unclear
4-factor PCC
Possible
Possible
Possible
PCC: prothrombin complex concentrate, PCCs with normal amounts of VII are known as 4-factor PCCs whilst the products
without VII are 3-factor PCCs
Kaatz S, et al. Am J Hematol. 2012 May;87 Suppl 1:S141-5. Pub Med PMID: 22473649.
48. Laboratory Testing New Oral Agents
Lab
Tests
Useful Dabigatran Rivaroxaban
Lab Test
Strong
ECT
Chromogenic
Anti-Xa
TT
Apixaban
Chromogenic
Anti -Xa
aPTT, PT
aPTT
Weak
PT / INR
ECT: Ecarin clotting time
Palladino M et al A J Hem 2012;87 Suppl:S127-S132
49. Optimal Candidates for New Drugs
Patients who:
•Find INR testing burdensome
•Despite adherence to provider
recommendations, have low ‘time-in-range’
•Can afford (or arrange to get) the new drugs
•Have normal renal function
50. Optimal Candidates for Warfarin
Patients who:
•Have (borderline) renal insufficiency
•Are taking stable dose of warfarin and do not
find INR testing burdensome
•Have access to self-testing machine
•Are concerned about the lack of an evidencebased reversal strategy
51. Choice of Anticoagulant Based on Patient Characteristics?
Characteristic
Drug Choice
Rationale
Mechanical or valvular AF
Warfarin
New agents not studied
Liver dysfunction with elevated
INR
Warfarin
New agents require hepatic metabolism
Poor compliance
Warfarin or nothing
Missed doses of greater consequence with shorter
acting agents
Stable on warfarin
Warfarin
Consider switching at patient request
CrCl < 30 mL/min
Warfarin
Such patients were excluded from trials with new
agents
CrCl of 30-50 mL/min
Rivaroxaban or
Apixaban
Oral Xa inhibitors are less affected by impaired
renal function than dabigatran
Dyspepsia or upper GI complaints
Rivaroxaban or
Apixaban
Dyspepsia in up to 10% given dabigatran
Recent GI bleed
Apixaban
More GI bleeding with dabigatran (150 mg BID) or
rivaroxaban than with warfarin
Recent ischemic stroke on
Warfarin
Dabigatran
Dabigatran (150 mg BID) associated with lowest
risk of ischemic stroke vs warfarin
Recent acute coronary syndrome
Rivaroxaban or
Apixaban
Small MI signal with dabigatran
Poor compliance with BID
regimen or desire for once daily
Rivaroxaban
Only oral agent that is currently once a day
Adapted/modified from Weitz & Gross, Hematology 2012:536-40
52. A Cardiologist's Perspective:
On The Evolving Treatment Paradigm for Stroke Prevention in AF
• Compared with warfarin, each of the 3 new
agents:
– Are at least as effective in preventing
stroke/systemic embolism
– Are associated with less intracranial bleeding
– Are associated with similar or less major bleeding
– Offer greater ease of use
53. Some Final Insane Musings
• Imagine if the novel anticoagulants had been
established therapy for some 6 decades and a new
drug appeared that:
– Was unpredictable in terms of patient therapeutic
response
– Had slow therapeutic onset and offset
– Had a narrow therapeutic window
– Required close monitoring via frequent blood tests
– Required frequent dose adjustment
– Was plagued by drug-drug and drug-food interactions
– Was associated with more intracranial haemorrhage
– Resulted in a 10% increase in mortality
Would anyone in their right mind think it had a chance of getting to
market and, if it did, would anyone prescribe it?
54. • “HAD WARFARIN INTRODUCED INTO THE
MARKET TODAY, THE US FDA WOULD HAVE
REJECTED”
-A FAMOUS CARDIOLOGIST DURING THE ESC
“BUT STILL, WARFARIN REMAINS OUR POOR MAN‟S CHOICE”
JAMA. 2001 May 9;285(18):2370-5.Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE.Source Division of Research, Kaiser Permanente of Northern California, 3505 Broadway, 12th Floor, Oakland, CA 94611, USA. axg@dor.kaiser.orgCONTEXT: Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described.OBJECTIVE: To estimate prevalence of atrial fibrillation and US national projections of the numbers of persons with atrial fibrillation through the year 2050.DESIGN, SETTING, AND PATIENTS: Cross-sectional study of adults aged 20 years or older who were enrolled in a large health maintenance organization in California and who had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997.MAIN OUTCOME MEASURES: Prevalence of atrial fibrillation in the study population of 1.89 million; projected number of persons in the United States with atrial fibrillation between 1995-2050.RESULTS: A total of 17 974 adults with diagnosed atrial fibrillation were identified during the study period; 45% were aged 75 years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years or older, prevalence of atrial fibrillation was higher in whites than in blacks (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently have atrial fibrillation. We project that this will increase to more than 5.6 million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50% of affected individuals aged 80 years or older.CONCLUSIONS: Our study confirms that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States. The number of patients with atrial fibrillation is likely to increase 2.5-fold during the next 50 years, reflecting the growing proportion of elderly individuals. Coordinated efforts are needed to face the increasing challenge of optimal stroke prevention and rhythm management in patients with atrial fibrillation.PMID: 11343485
Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Circulation. 2004 Aug 31;110(9):1042-6. Epub 2004 Aug 16.PMID: 15313941 Circulation. 2004 Aug 31;110(9):1042-6. Epub 2004 Aug 16. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ.Source Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore Drive, Suite 1102, Chicago, IL, 60611, USA. dlj@northwestern.eduBACKGROUND: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated.METHODS AND RESULTS: We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%.CONCLUSIONS: Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.
Chest. 2010 Feb;137(2):263-72. Epub 2009 Sep 17.Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ.Source University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK. g.y.h.lip@bham.ac.ukBACKGROUND: Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included.METHODS: We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF.RESULTS: Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003).CONCLUSIONS: Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.Comment inCHA2DS2-VASc risk scheme: not ready for clinical use. [Chest. 2010]Obstructive sleep apnea is a risk factor for stroke and atrial fibrillation. [Chest. 2010]