1. The document discusses Valentin Fuster's disclosure information and level of involvement as chair of BG Medicine. It then covers several topics related to atrial fibrillation (AF) and antithrombotic treatment including Virchow's triad, different disease compartments, bleeding risks, and new directions in treatment.
2. Several studies and trials are summarized related to anticoagulation therapy for AF, risks of bleeding, outcomes for different antithrombotic regimens, and prevalence and management of AF in clinical practice based on various surveys.
3. The document provides an overview of Valentin Fuster's disclosure statement and then reviews the literature on antithrombotic treatment and
Methods: The current clinical study was conducted at Gaza city. It involved 90 patients who were scheduled for coronary angioplasty procedure. The patients were divided into three groups: The first group (n = 30), underwent BMS implantation and received colchicine 0.5 mg twice daily for six months. The second group (n = 30), underwent BMS implantation alone. The third group (n = 30) underwent DES implantation. All the patients were followed up for six months. The primary endpoint was clinical ISR at 6months. Secondary endpoints included Target Vessel Revascularization (TVR) and Stent Thrombosis (ST).
Methods: The current clinical study was conducted at Gaza city. It involved 90 patients who were scheduled for coronary angioplasty procedure. The patients were divided into three groups: The first group (n = 30), underwent BMS implantation and received colchicine 0.5 mg twice daily for six months. The second group (n = 30), underwent BMS implantation alone. The third group (n = 30) underwent DES implantation. All the patients were followed up for six months. The primary endpoint was clinical ISR at 6months. Secondary endpoints included Target Vessel Revascularization (TVR) and Stent Thrombosis (ST).
Multicenter prospective study in several Spaniard hospital
Anemia and iron deficit in preoperative study
Presented at NATA meeting at Dublin, April 2016
Percutaneous Coronary Intervention [PCI] has been a revolutionary advance in cardiology, and many lives have been saved as a result of the widespread application of primary PCI. However, elective PCI has not yet been proven to save lives or reduce the risk of myocardial infarction. Despite this lack of
evidence, elective PCI has been misused and in some cases, abused for nonmedical reasons. The considerable cost of elective PCI can be reduced, and the resources could potentially be utilized for better public health outcomes. The following.article intends to highlight the lack of evidence supporting the use of elective PCI, which is a problem not only in North America and Europe but also throughout the world.
Better regulation of the elective PCI procedure could reduce health care expenditures and divert resources to cardiovascular disease prevention.
Rivaroxaban for thromboprophylaxis after Hospitalization for Medical IllnessShadab Ahmad
Anticoagulant prophylaxis reduces the risk of in-hospital venous thromboembolism by 50 to 60% but is rarely continued after discharge in accordance with current guidelines
Reducing Perioperative Cardiac Risk: Do Beta blockers Help?Terry Shaneyfelt
Review of the effect of beta blockers on perioperative cardiac events including updated recommendations by the ACC/AHA (August 2014. Watch my YouTube video (http://youtu.be/WPLXDm9Nzoc) describing these slides.
Multicenter prospective study in several Spaniard hospital
Anemia and iron deficit in preoperative study
Presented at NATA meeting at Dublin, April 2016
Percutaneous Coronary Intervention [PCI] has been a revolutionary advance in cardiology, and many lives have been saved as a result of the widespread application of primary PCI. However, elective PCI has not yet been proven to save lives or reduce the risk of myocardial infarction. Despite this lack of
evidence, elective PCI has been misused and in some cases, abused for nonmedical reasons. The considerable cost of elective PCI can be reduced, and the resources could potentially be utilized for better public health outcomes. The following.article intends to highlight the lack of evidence supporting the use of elective PCI, which is a problem not only in North America and Europe but also throughout the world.
Better regulation of the elective PCI procedure could reduce health care expenditures and divert resources to cardiovascular disease prevention.
Rivaroxaban for thromboprophylaxis after Hospitalization for Medical IllnessShadab Ahmad
Anticoagulant prophylaxis reduces the risk of in-hospital venous thromboembolism by 50 to 60% but is rarely continued after discharge in accordance with current guidelines
Reducing Perioperative Cardiac Risk: Do Beta blockers Help?Terry Shaneyfelt
Review of the effect of beta blockers on perioperative cardiac events including updated recommendations by the ACC/AHA (August 2014. Watch my YouTube video (http://youtu.be/WPLXDm9Nzoc) describing these slides.
Cardiovascular risk evaluation and management before renal transplantation sl...Christos Argyropoulos
Presentation focused on pre-operative evaluation of Major Adverse Cardiac Events prior to renal transplantation.
Modified from a presentation I gave in 2007; compared to the original there is a less enthusiastic endorsement of a peri-operative fixed dose beta blockade administration strategy given the discrepant results of the POISE and DECREASE-II studies
A presentation regarding a analysis of the marketplace for stents and also how Abbott could enter the market with their new stent technology in order to acquire the most amount of customers.
Dyslipidemia -Assessment and management based on evidence SYEDRAZA56411
This presentation is focused on cardiovascular risk assessment and application of evidence based principles in choosing right intensity statin therapy for patients with dyslipidemia
Ponencia presentada por la Dra. Marisol Bravo Amaro en el CardioTV Live ‘Debatiendo estrategias actuales para la reducción de eventos CV tras síndrome coronario agudo reciente’, realizado el 21 de mayo de 2024 en la Casa del Corazón
Ponencia presentada por el Dr. Armando Oterino Manzanas en el CardioTV Live ‘Debatiendo estrategias actuales para la reducción de eventos CV tras síndrome coronario agudo reciente’, realizado el 21 de mayo de 2024 en la Casa del Corazón
Ponencia presentada por la Dra. Miriam Martín Toro en el CardioTV Live ‘Debatiendo estrategias actuales para la reducción de eventos CV tras síndrome coronario agudo reciente’, realizado el 21 de mayo de 2024 en la Casa del Corazón
Ponencia presentada por los Dres. M.ª Dolores Mesa Rubio, Javier Mora Robles, Margarita Reina Sánchez, M.ª José Castillo Moraga y José Luis Bianchi Llave en el CardioTV Focus, publicado el 25 de abril de 2024 en la Casa del Corazón (Madrid).
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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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
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
- 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
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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.
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
2. ATHERO-THROMBOSIS- 2009 NOVEL ANTITHROMBOTIC RX - AF AS A MODEL 1. Basic Framework – Virchow’s Triad 2. Vascular Compartment – Platelets vs Fibrin 3. Antithrombotics – The Bleeding Problem 4. Antithrombotic Approaches – The Six Steps 5. New Directions – Non Pharmacological ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700 AHA Guidelines Handbook – Ed. V Fuster 2009
3.
4. ATHERO-THROMBOSIS- 2009 NOVEL ANTITHROMBOTIC RX - AF AS A MODEL 1. Basic Framework – Virchow’s Triad 2. Vascular Compartment - Platelet vs Coagulation 3. Antithrombotics – The Bleeding Problem 4. Antithrombotic Approaches – The Six Steps 5. New Directions – Non Pharmacological ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700 AHA Guidelines Handbook – Ed. V Fuster 2009
8. WASHED RED BLOOD CELLS (HEMATOCRIT = 58%) AND FIBRINOGEN = 493MG/DL R A Merino et al JACC 1992 ;20:1661 R Rastegar et al., JACC 2003 ;41:603 STASIS – SEC – ACTIVATION OF THE COAGULATION SYSTEM
9. ATHERO-THROMBOSIS- 2009 NOVEL ANTITHROMBOTIC RX - AF AS A MODEL 1. Basic Framework – Virchow’s Triad 2. Vascular Compartment - Platelet vs Coagulation 3. Antithrombotics – The Bleeding Problem 4. Antithrombotic Approaches – The Six Steps 5. New Directions – Non Pharmacological ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700 AHA Guidelines Handbook – Ed. V Fuster 2009
10. 1) RISK FACTORS FOR MAJOR BLEEDING IN PATIENTS WITH ACUTE CORONARY SYNDROME Eikelboom et al. Kinnaird et al. Morcucci et al. Rao et al. Manoukian et al. Risk factor 2006 (N=34,126) 2003 (N=10,974) 2003 (N=24,045) 2005 (N=26,452) 2007 (N=13,819) Older age √ √ √ √ √ Diabetes mellitus √ √ √ √ √ Renal dysfunction √ √ √ √ √ Female sex √ √ √ √ History of hypert. √ √ √ √ SBP or MAP √ √ History of stroke √ √ M Cohen. Mayo Clin Proc 2009 ; 84:149
11. 1) RELATIONSHIP BETWEEN AGE AND FREQUENCY OF BLEEDING (95% CI) IN CHARISMA PATIENTS RECEIVING PLACEBO CHARISMA (PB Berger, DL Bhatt, V Fuster et al.,) 2009 (Subm) 0.15 0.14 0.13 0.12 0.11 0.10 0.09 0.08 0.07 0.06 0.05 0.04 0.03 0.02 0.01 0.00 39 41 43 45 47 49 51 53 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83 85 87 89 91 93 95 600 550 500 450 350 250 150 50 400 300 200 100 0 Number of Patients Predicted Bleeding Probability Age
12. Cardiovascular Events Hazard Ratio No Bleed Bleed HR (95% CI) p-value n (%) n (%) CV death/MI/stroke 949 (6.3) 59 (15.2) 2.518 (1.936, 3.276) <0.001 CV death 384 (2.5) 74 (15.5) 6.588 (5.136, 8.449) <0.001 Non-fatal MI 271 (1.8) 15 (3.9) 2.259 (1.343, 3.800) 0.002 Non-fatal stroke 294 (1.9) 3 (0.8) 0.412 (0.132, 1.286) 0.115 All-cause death 630 (4.2) 106 (22.2) 5.791 (4.714, 7.115) <0.001 CV death/MI/stroke/hosp 2464 (16.3) 61 (19.3) 1.183 (0.918, 1.525) 0.194 Hospitalization 1707 (11.3) 21 (6.6) 0.592 (0.385, 0.910) 0.016 2) CHRONIC EVENT RATES OF PATIENTS WHO SUFFERED A MODERATE OR SEVERE BLEED vs THOSE WHO DID NOT 0 1 2 3 4 5 6 7 8 9 CHARISMA (PB Berger, DL Bhatt, V Fuster et al.,) 2009 (Subm)
13. Linking Post-PCI Bleeding With Increased Mortality BJ Doyle et. al., J Am Coll Cardiol . 2009 ;53:2019 .
14. Impact of Storage on RBCs & Tissue Oxygen Delivery BJ Doyle et. al., J Am Coll Cardiol . 2009 ;53:2019
15. Kaplan-Meier Estimates of Survival and Death After Transfusion of Older or Newer Blood DH Adams et. al. JACC 2009 ;53:2389. CG Koch et. al. N Engl J Med . 2008 ;358:1229 .
16. 3) MAJOR BLEEDING IN MATCHED COHORT TRIALS OF STENTING Study Warf+Asp+Clop Asp+Clop RR (fixed) n/N n/N 95% CI De Eugenio et al . 14/97 3/97 Kanaiginen et al. 18/239 4/239 Khurram et al. 7/107 9/107 Total 95% CI 443 443 0.01 0.1 1 10 100 Favours Triple Therapy Favours DoubleTherapy A Sourgounis et al., Circ 2009 ; 119:1682
17. 3a) Efficacy and Safety of Drug-Eluting Stent Use in Patients With Atrial Fibrillation We reviewed 604 patients with AF who had undergone percutaneous coronary intervention with stent over a period of 7 years (January 2001 - January 2008). On the basis of this study, the routine use of DES in patients with AF does not seem to be justified. A higher risk of major bleeding with DES in comparison with BMS raises the possibility that DES should be limited to lesions or patients with a high risk of restenosis. JM Ruiz-Nodar et al., Eur Heart J 2009 ; 30:932
18. 3b) TRIPLE THERAPY WITHIN TARGETED INR VALUES 2.0 TO 2.5 AND THOSE WHO WERE NOT (>2.5) CUMULATIVE EVENT-FREE SURVIVAL FROM OVERALL BLEEDING 0 200 300 450 600 Days 100 90 90 90 90 90 Bleeding event free survival (%) Dual therapy (n=102) Triple therapy (INR: 2.0-2.5) (n=81) Triple therapy (INR > 2.5) (n=21) 66.7% 95.1% 95.1% R Rossini, DJ Angiolillo et al., AJC 2008; 102:1618 (non-randomized)
19. 3c) DES-T (N=6816): CHANGE IN THE RISK OF STENT THROMBOSIS IN RELATION TO CLOPIDOGREL TREATMENT DURATION S Schultz et al., EHJ 2009 (In Press) (Munich) 0 6 12 18 24 30 36 42 48 Clopidogrel treatment duration (months) 0 0.1 0.2 0.3 0.4 Risk of ST within 4 years (%) 0 50 100 150 200 days 0.0 0.025 0.05 0.075 0.10
20. ATHERO-THROMBOSIS- 2009 NOVEL ANTITHROMBOTIC RX - AF AS A MODEL 1. Basic Framework – Virchow’s Triad 2. Vascular Compartment - Platelet vs Coagulation 3. Antithrombotics – The Bleeding Problem 4. Antithrombotic Approaches – The Six Steps 5. New Directions – Non Pharmacological ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700 AHA Guidelines Handbook – Ed. V Fuster 2009
21. 1) PREVALENCE / INCIDENCE OF ADULTS WITH AF IN THE US 1995 AND 2050 1990 1995 2000 2005 2050 2010 2045 2015 2020 2025 2030 2035 2040 Year Adults with Atrial Fibrillation in millions 0 1 2 3 4 5 6 7 2.08 2.26 2.44 2.68 2.94 3.33 3.50 4.34 4.78 5.16 5.42 6.07 ATRIA (AS Go et al.) JAMA 2001 ; 285: 2370 (Kaiser Permanente, North Ca) Age -1% at 60 y….+ 5% decade- , Cardiac Failure (1-25%) etc
22. 40-49 5 0-59 6 0-69 7 0-79 8 0-89 0 1 2 3 4 5 6 7 8 Stroke rate (%/year) 1) STROKE RATES IN RELATION TO AGE AMONG PATIENTS WITH ATRIAL FIBRILLATION Framingham - PA Wolf et al., Ann Int Med 1987;147:1561 – 10% Age Unrelated to Left Atrium (CVD, other Cardiac, aorta) 25% Bogousslavsky J et al & Miller VT et al Neurol 1990 ;40:1046 & 1993;43:32
23. 2) Meta-analysis - Antithrombotic Therapy in Atrial Fibrillation (AF) Thirteen new trials are available since a 1999 meta-analysis of antithrombotic agents for stroke prevention in patients with AF. This updated meta-analysis shows that adjusted-dose warfarin reduces stroke risk by 64% (6 trials) and antiplatelet agents reduce stroke risk by 22% (8 trials). Meta-analysis of 12 trials shows that adjusted-dose warfarin is more effective than antiplatelet therapy, but it doubles the risk for major extracranial and intracranial hemorrhage. But, these adverse events were only 0.2% per year. Additional trials are unlikely to change current estimates of the effectiveness of vitamin K antagonists and antiplatelet agents RG Hart et al., Ann Int Med 2007; 146:857 (San Antonio, Tx)
24. 3) ATRIAL FIBRILLATION - RISK OF STROKE BY CHAD * SCORE CHAD Index Antithrombotics High Risk: TE, MS, PHV Warfarin INR 2.0-3.5 2 RF Warfarin INR 2-3 Moderate Risk: 1 RF ASA 81-325mg Warfarin INR 2-3 (<EF) Low Risk: 0 RF ASA 81-325 mg * RF: C.Fail./ EF <35% 1 , Hypert. 1 , Age >75 1 , Diabetes 1 , ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700
25. 4a) USE OF ORAL ANTICOAGULANT THERAPY TO PREVENT STROKE ATRIAL FIBRILLATION - RESULTS OF RECENT SURVEYS ATRIA: Anticoagulation and Risk Factors in Atrial Fibrillation; NABOR: National Anticoagulation Benchmark and Outcomes Report. SJ Connolly, S Yusuf et al.Circ 2007 ; 116:450 Year Treated w/ Warfarin, % Published Survey Population (Patient Status) 1999 ATRIA Study 11,082 US patients large HMO - No 60 2005 NAROR Study 945 US patients from teaching, 55 community, and VA hospital 2006 Euro Heart Survey 2706 outpatients in 35 European 64 countries 2006 Hylek et al. 402 US patients, 55 years old, 51 learning hospital 2006 Birman-Deych et al. 16,007 US Medicare patients 49
26. 4a) Management of AF in Clinical Practice Prescription of vitamin K antagonists n = 11,379 ATRIA cohort (managed care system, California, U.S.A.) Go AS, et al. JAMA 2003; 290: 2685 n = 5,333 EuroHeart survey Nieuwlaat R, et al. Eur Heart J 2005; 29: 1181 n = 23,657 Medicare cohort, U.S.A. Birman-Deych E, et al. Stroke 2006; 37: 1070 vitamin K antagonists no anticoagulation
27. 4b) EURO HEART SURVEY ON AF ANTITHROMBOTIC Rx AT DISCHARGE 1 (2003-2004) 0 20 40 60 80 100 % Patients OAC OAC + antiplatelet Antiplatelet Other antithrombotic No antithrombotic 1 35 Countries,182 Hosp, 5333 pts - R Nieuwlaat et al.EHJ 2007 ; 26:2422 US - SB Rowan et al., JACC 2007 ; 49:1561 Ineligible (n=517) Eligible (n=517)
28. 4c) PROPORTION OF PATIENTS PERSISTING WITH WARFARIN TREATMENT OVER TIME STRATIFIED BY AGE AND CHADS 2 SCORE 100 80 60 40 20 0 % Warfarin by age 0 2 4 6 Time (years after diagnosis) 100 80 60 40 20 0 % Warfarin by CHADS2 score 0 2 4 6 Time (years after diagnosis) Age 40-64 Age 65-69 Age 70-74 Age 75-79 Age 80-84 Age 85+ CHADS2=0 CHADS2=3 CHADS2=6 CHADS2=1 CHADS2=4 CHADS2=2 CHADS2=5 UK-GPs: n=41910 pts with chronic AF AM Gallagher et al., J Thromb Hemost 2008 ; 6:1500
29. 4d) Anticoagulation with Warfarin Intensity Often Outside the Target Range Ansell J, et al . J Thromb Thrombolysis 2007; 23: 83 International Study of Anticoagulation Management % Time in Target Range 0 20 40 60 80 100 U.S. Canada France Italy Spain INR <2 INR 2–3 INR >3
30. 4d) AF - RELATIONSHIP BETWEEN THE OR (RELATIVE TO C+A) OF STROKE, MI, SYSTEMIC EMBOLISM, VASCULAR DEATH, OR MAJOR HEMORRHAGE AND TTR ACTIVE W (SJ Connolly et al.) Circ 2008 ; 118:2029 – Dot = Country 4.0 3.5 2.0 2.5 2.0 1.5 1.0 0.5 0.0 40 50 60 70 80 Not TTR (%) OR for Primary + Major Bleed OAC
31. Thrombin SCH 530348 AZD0837 ADP ATP P2X 1 P2Y 1 Aspirin P2Y 12 Abciximab Eptifibatide Tirofiban Stable/sustained platelet aggregation Initiation of transient platelet aggregation Stable/sustained platelet aggregation Cross-linking of adjacent platelets TXA 2 and prothrombotic (ADP) molecules Shape change PAR-1 Gq Gr shape change granule release fibrinogen “ GPIIb/IIIa receptor activation” PLC [Ca++] PKC augmented granule release and TXA 2 production Adenyl cyclase downregulation /↓ camp Gi-coupled signaling pathways Gi-coupled signaling pathway Gq and Gi-coupled signaling pathways Ca++ flux COX-1 TXA 2 Shape change Gq G 12 ← Ticlopidine ← Clopidogrel ← Prasugrel Active metabolite Ticagrelor Cangrelor IV hepatic biotransformation Gi 5)
32. The ACTIVE Trial Clopidogrel + Aspirin Atrial Fibrillation + Risk Factors X Double-blind Superiority n~7,500 Open-label Non-inferiority n=6,500 Anticoagulation-eligible OAC Contraindications or Unwilling Irbesartan, 300 mg/d vs. Placebo n ~9,000 Primary outcome : Stroke, systemic embolism, MI or cardiovascular death ACTIVE - W ACTIVE - A ACTIVE - I Risk Factors : Age 75, hypertension, prior stroke/TIA, LVEF<45%, PAD, age 55-74 + CAD or diabetes VKA (INR 2-3) Clopidogrel + Aspirin Aspirin + Placebo Clopidogrel + Aspirin
33. Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation 0 1 2 3 4 0.0 0.1 0.2 0.3 0.4 Aspirin Clopidogrel + aspirin Years Cumulative incidence 0 1 2 3 4 0.0 0.1 0.2 0.3 0.4 Aspirin Clopidogrel + aspirin Years Cumulative incidence Primary Outcome Stroke The Active A Invest . N Engl J Med 2009 ; 360 (In Press) P<0.001 P<0.0001 Major bleeding : 2.0% per year clopidogrel and 1.3% per year placebo (p<0.001).
34. 0 2 4 6 8 10 12 0 2 4 6 8 10 12 0 2 4 6 8 10 12 0 5 10 15 Ticagrelor Clopidogrel Clopidogrel Ticagrelor Months Months Cumulative Incidence of Primary End Point (%) Cumulative Incidence of Major Bleeding (%) Cumulative Kaplan–Meier Estimates of the Time to the First Major Bleeding End Point, According to Study Criteria Cumulative Kaplan–Meier Estimates of the Time to the First Adjudicated Occurrence of Primary Efficacy End Point PLATO (Lars Wallentin et al.,) N Engl J Med 2009 ; 361:1 ACS (N=18624) - TICAGRELOR (180LD-90mgx2d ) VS CLOPIDOGREL (300/600LD-75mgx2d ) End Point: Death (Vascular), MI, Stroke – Ticagrelor: Early reversibility (CABG etc)
35. 6) Investigational Anticoagulant Targets TFPI (tifacogin) Idraparinux Rivaroxaban Apixaban LY517717 YM150 DU-176b Betrixaban TAK 42 Dabigatran ORAL PARENTERAL DX-9065a Otamixaban Xa IIa TF/VIIa X IX IXa VIIIa Va II (thrombin) Fibrin Fibrinogen AT APC (drotrecogin alfa) sTM (ART-123) Adapted from Weitz JI. Thromb Haemost 2007 ; 5 Suppl 1:65-7. TTP889 APC activated protein C AT antithrombin sTM soluble thrombomodulin TF tissue factor FPI tissue factor pathway inhibitor
36. 5B)ANTITHROMBOTIC REGIMENS UNDER INVESTIGATION FOR CHRONIC TREATMENT OF PATIENTS WITH ATRIAL FIBRILLATION Phase 3 trial in AF Drug Class Phase 2 trial in AF Non-inf trial vs OAC Sup trial vs aspirin Dabigatran Dir thromb. inhib Done NCT00262600 (RE-LV) Not done Results 2009 AZD0837 Plat.-thromb. inhib Not done Planned Rivaroxaban Oral Xa inhib Not done NCT00403767 Not done Results 2010 Apixaban Oral Xa inhib Not done NCT00412984 NCT00496769 (AVERROES) (ARISTOTLE) Results 2010 Results 2010 Betrixoban Oral Xa inhib Plan 10/2008 ‒ Not done Du-176b Oral Xa inhib Done NCT00504556 Not done Biotimyl. Idrap. Parent Xa inhib Not done NCT00580216 ( BOREALIS) Not done Results 2010? R Nicuwlaat, SJ Connolly, Heart 2009; 95:95
37. RE-LY ® Trial R andomized E valuation of L ong-term Anticoagulant Therap y with Dabigatran Etexilate Primary objective: noninferiority vs. warfarin Observation period: minimum 1, mean 2, maximum 3 years Primary endpoint: all stroke + systemic embolism Safety measure: bleeding during treatment Connolly SJ, Ezekowitz MD et al. N Engl J Med 2009; 361, August 30, Open-label n = 18,113 Non-valvular AF + > 1 stroke risk factor Warfarin (INR 2.0-3.0) n = 6,022 Dabigatran 110 mg bid n = 6,015 Dabigatran 150 mg bid n = 6,076 Blinded
38. RE-LY ® Trial Primary Events Event Rate (%/year) p <0.001 (Noninferiority) p <0.001 (Superiority) All Strokes and Systemic Embolic Events Connolly SJ, Ezekowitz MD et al. N Engl J Med 2009; 361, August 30,
39. RE-LY ® Trial All-Cause Mortality Event Rate (%/year) p = NS p = 0.051 Connolly SJ, Ezekowitz MD et al. N Engl J Med 2009; 361, August 30, 2009
40. RE-LY ® Trial Hemorrhagic Stroke Events Event Rate (%/year) p <0.001 p <0.001 Connolly SJ, Ezekowitz MD et al. N Engl J Med 2009 ; 361, August 30
41. RE-LY ® Trial All Major Bleeding Event Rate (%/year ) p = 0.003 p = NS Hgb > 2 g/dl or Transfusion > 2 units or Critical Site Connolly SJ, Ezekowitz MD et al. N Engl J Med 2009 ; 361, August 30 p = 0.04
42.
43. 5B)ANTITHROMBOTIC REGIMENS UNDER INVESTIGATION FOR CHRONIC TREATMENT OF PATIENTS WITH ATRIAL FIBRILLATION Phase 3 trial in AF Drug Class Phase 2 trial in AF Non-inf trial vs OAC Sup trial vs aspirin Dabigatran Dir thromb. inhib Done NCT00262600 (RE-LV) Not done Results 2009- AZD0837 Plat.-thromb. inhib Not done Planned Rivaroxaban Oral Xa inhib Not done NCT00403767 Not done Results 2010 Apixaban Oral Xa inhib Not done NCT00412984 NCT00496769 (AVERROES) (ARISTOTLE) Results 2010 Results 2010 Betrixoban Oral Xa inhib Plan 10/2008 ‒ Not done Du-176b Oral Xa inhib Done NCT00504556 Not done Biotimyl. Idrap. Parent Xa inhib Not done NCT00580216 ( BOREALIS) Not done Results 2010? R Nicuwlaat, SJ Connolly, Heart 2009; 95:95
44. APIXABAN AND ACUTE CORONARY SYNDROME Composite of CV Death, MI, Severe Rec. Ischemia , and Ischemic Stroke Composite of Major and Clinically Relevant Nonmajor Bleeding APPRAISE Steering Committee and Invest. – Circ 2009; 119:2877 0 4 8 12 16 20 24 28 0 0.02 0.04 0.06 0.08 0.1 Weeks from Randomization Proportion with ISTH Major or CRNM Bleeding Apix 10 mg OD Apix 2.5 mg BID Placebo 0 4 8 12 16 20 24 28 0 0.02 0.04 0.06 0.08 0.1 Weeks from Randomization Proportion with CV Death, MI, SRI, or Stroke Apix 10 mg OD Apix 2.5 mg BID Placebo
45. APIXABAN AND CLOPIDOGREL CV Death, MI, Severe Ischemia And Ischemic Stroke Major or Clinically Relevant Nonmajor Bleeding APPRAISE Steering Committee and Invest. – Circ 2009 ; 119:2877 0.1 0.08 0.06 0.04 0.02 0 Clopidogrel No Clopidogrel 0.03 0.04 0.02 0.03 0.07 0.09 Placebo Apixaban 2.5 mg BID Apixaban 10 mg OD N 453 230 241 146 85 74 0.16 0.12 0.08 0.04 0 Clopidogrel No Clopidogrel 0.07 0.09 0.13 0.15 0.06 0.05 N 462 232 243 149 85 75
46. ATHERO-THROMBOSIS- 2009 NOVEL ANTITHROMBOTIC RX - AF AS A MODEL 1. Basic Framework – Virchow’s Triad 2. Vascular Compartment - Platelet vs Coagulation 3. Antithrombotics – The Bleeding Problem 4. Antithrombotic Approaches – The Six Steps 5. New Directions – Non Pharmacological ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700 AHA Guidelines Handbook – Ed. V Fuster 2009
47. 1) LAA Closure: Clinical Outcomes Holmes, Reddy, et al. Lancet 2009 ; 374:534. PROTECT-AF Trial LA LV Watchman Device Follow-Up Non-Valvular AF CHADs ≥ 1 Randomization (1:2) Warfarin Watchman Barbs Engage LAA Wall 160 µ PET fabric
50. LAA Closure: Pericardial Suture Ligation V Reddy et al 2009 Pre-Ligation LAA Mitral Valve Post-Ligation Mitral Valve Sternum Needle Liver RV LV Provided by: E Sosa, M Scanavacca, A d’Avila
51. 2) D Display and Integration of Scar Within the Electroanatomic Map FM Bogun et. al. J Am Coll Cardiol . 2009 ;53:1138.
52. AF - CORRELATION BETWEEN ENHANCEMENT ON DE-MRI AND LOW-VOLTAGE REGIONS ON ELECTROANATOMIC (EA) MAP 40 30 20 10 0 0 5 10 15 20 25 30 35 40 45 Extent of Delayed Enhancement (MRI) Low Voltage Tissue (EA Map) R 2 =0.67 P<0.05 95% CI (0.81-1.30) RS Oakes et al., Circulation 2009; 119:1758 (Utah)
53. AF - PATIENTS IN NSR AFTER LA ABLATION. COX REGRESSION CURVES FOR PATIENTS WITH DIFFERENT DEGREES OF DE-MRI RS Oakes et al., Circulation 2009 ; 119:1758 (Utah) 100 200 300 400 500 Time since ablation (days) Proportion of Patients in Sinus Rhythm 0.00 0.25 0.50 0.75 1.00 Mild Moderate Extensive Enhancement
54. ATHERO-THROMBOSIS- 2009 NOVEL ANTITHROMBOTIC RX - AF AS A MODEL 1. Basic Framework – Virchow’s Triad 2. Vascular Compartment - Platelet vs Coagulation 3. Antithrombotics – The Bleeding Problem 4. Antithrombotic Approaches – The Six Steps 5. New Directions – Non Pharmacological ACC/AHA/ESC (Fuster V et al) Circ 2006; 114:700 AHA Guidelines Handbook – Ed. V Fuster 2009
Editor's Notes
A retrospective, multicentre cohort study, conducted in the US, Canada, France, Italy and Spain, randomly recruited 1511 patients from representative practices (routine medical care in the US, Canada and France and anticoagulation clinics in Italy and Spain). Medical records were used to extract data relating to their oral anticoagulant care. All patients included in this study received oral anticoagulation for at least 60 days. These data show that oral anticoagulation care varied considerably and patients spent less between 50.8% and 60.0% of their time within the target INR of 2 – 3. The percentage of time within this range varied from 58.1% to 69.5%. The mean time spent in range did not differ by age or sex. Ansell J et al . Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM). J Thromb Thrombolysis . 2007;23:83–91.
Source: Turpie State of the art presentation EFORT-08 (rivaroxaban, apixaban and dabigatran highlighted and all the others greyed out) Reference Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost 2005;3:1843–1853 All of the drugs in the above figure are to be found in Weitz and Bates (2005) in Figure 2, apart from: Apixaban – this was called BMS-562247 in the original figure Betrixaban and YM150 – see Graham Turpie’s review paper: Turpie AGG. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008;29:155–165 Otamixaban – Guertin KR, Choi YM. The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development. Curr Med Chem 2007;14:2471–2481
Note the initial higher event rate in the device group…this was procedure-related stroke. That is, mostly air embolism during device implantation. Note that the large 12Fr sheath used to implant the device needs careful monitoring to prevent this (there were a total of 5 procedure-related strokes in the Device group).’ In the “Post-Procedure analysis” (a pre-specified analysis that looks at what happens if you ignore events on the day of the procedure), without these early peri-procedural strokes, the RR is now .45 and the Device strategy is actually superior to Warfarin
But there is also an important safety signal…predominantly early (most frequent complication was pericardial effusion)