The document summarizes key findings from the CHARISMA clinical trial which evaluated the benefits of dual antiplatelet therapy with clopidogrel and aspirin compared to aspirin alone in patients at risk of cardiovascular events. The trial found no significant reduction in the primary endpoint of heart attack, stroke or cardiovascular death in the overall population, but did see a reduction in the secondary endpoint which included hospitalizations. Subgroup analysis found dual therapy beneficial for patients with established cardiovascular disease but not for those with multiple risk factors only. The REACH registry aims to study characteristics and management of stable patients at risk of atherosclerotic events globally.
Platelet Aggregation Inhibitor Ticagrelor(274693-27-5) for saleticagrelor
Ticagrelor(274693-27-5) is a platelet aggregation inhibitor, It keeps the platelets in your blood from coagulating (clotting) to prevent unwanted blood clots. Visit: http://www.aasraw.com/products/ticagrelor-powder/
PLATO (Platelet Inhibition and Patient Outcomes)theheart.org
- Background:
Ticagrelor, a new antiplatet agent and not a thienopyridine, has a unique mechanism of action in that it is reversible
- Population and treatment:
18 624 ACS patient, with or without ST-segment elevation, randomized in a double-blind, double-dummy fashion to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg thereafter) for one year
Patients also received aspirin 75 mg to 100 mg day, unless they could not tolerate the drug
- Primary outcome:
A composite of death from vascular causes, MI, or stroke
See the article at http://www.theheart.org/article/995621.do
Platelet Aggregation Inhibitor Ticagrelor(274693-27-5) for saleticagrelor
Ticagrelor(274693-27-5) is a platelet aggregation inhibitor, It keeps the platelets in your blood from coagulating (clotting) to prevent unwanted blood clots. Visit: http://www.aasraw.com/products/ticagrelor-powder/
PLATO (Platelet Inhibition and Patient Outcomes)theheart.org
- Background:
Ticagrelor, a new antiplatet agent and not a thienopyridine, has a unique mechanism of action in that it is reversible
- Population and treatment:
18 624 ACS patient, with or without ST-segment elevation, randomized in a double-blind, double-dummy fashion to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg thereafter) for one year
Patients also received aspirin 75 mg to 100 mg day, unless they could not tolerate the drug
- Primary outcome:
A composite of death from vascular causes, MI, or stroke
See the article at http://www.theheart.org/article/995621.do
Impact of access site on bleeding and ischemic events in patients with non-ST-segment elevation myocardial infarction treated with prasugrel at the time of percutaneous coronary intervention or as pretreatment at the time of diagnosis: the ACCOAST access substudy
Excelencia en el Manejo del Síndrome Coronario Agudo.
Cambiando el paradigma de tratamiento de los pacientes con Cardiopatía Isquémica.
15/04/2015 18:00h - 20:00h Casa del corazón. Sociedad Española de Cardiología
http://cvvt.secardiologia.es
Antiagregación en los pacientes con Cardiopatía Isquémica
Dr. Héctor Bueno Zamora. Hospital General Universitario Gregorio Marañón (Madrid)
Pierre Janin talks targets in neuro-icu, zoning in on blood pressure management in patients with ICH. This resource was recorded at Bedside Critical Care Conference 4.
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
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.
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.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
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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
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.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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.
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
1. CVD Critical Pathways Group 2006 Teleconferences March 22, 2006 This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership.
2. Faculty Gregg C. Fonarow, MD Eliot Corday Professor of Medicine and Cardiovascular Science Director, Ahmanson-UCLA Cardiomyopathy Center UCLA Division of Cardiology UCLA Medical Center Los Angeles, California
3. The Network for Continuing Medical Education requires that CME faculty disclose, during the planning of an activity, the existence of any personal financial or other relationships they or their spouses/partners have with the commercial supporter of the activity or with the manufacturer of any commercial product or service discussed in the activity. Disclosure Statement
4. Gregg C. Fonarow, MD, has served as a consultant to and has received research support and honoraria from Bristol-Myers Squibb Company, GlaxoSmithKline, Merck & Co., Inc., Pfizer Inc, sanofi-aventis, Schering-Plough Corporation, and Scios, Inc. The team from Aurora Health Care reports no such relationships. Faculty Disclosure Statement
5.
6. Highlights From the American College of Cardiology 2006 Annual Scientific Session Gregg C. Fonarow, MD
10. C lopidogrel for H igh A therothrombotic R isk and I schemic S tabilization, M anagement, and A voidance (CHARISMA): Study Design Double-blind treatment up to 1040 primary efficacy events occur* Aspirin 75–162 mg o nce daily Clopidogrel 75 mg o nce daily Placebo 1 tab o nce daily Aspirin 75–162 mg o nce daily Final study visit (fixed study end date) 1-month visit 3-month visit Patients 45 years or older who are at high risk of atherothrombotic events R = randomization. N=15,603 R Bhatt DL, et al. Am Heart J . 2004;148:263-268. *Event-driven trial: primary efficacy outcome of vascular death, MI, stroke Visits every 6 months (12 m, 18 m…), and intermediate phone calls in between (15 m, 21m…) 6-month visit
11. Overall Population: Primary Efficacy Outcome (MI, Stroke, or CV Death) † † First Occurrence of MI (fatal or non-fatal), stroke (fatal or non-fatal), or cardiovascular death *All patients received ASA 75-162 mg/day § The number of patients followed beyond 30 months decreases rapidly to zero and there are only 21 primary efficacy events that occurred beyond this time (13 clopidogrel and 8 placebo) Adapted with permission from Bhatt DL, et al. N Engl J Med. 2 006;354. Placebo + ASA* 7.3% Clopidogrel + ASA* 6.8% RRR: 7.1% [95% CI: -4.5%, 17.5%] P = 0.22 Months since randomization § 0 2 4 6 8 0 6 12 18 24 30 Cumulative event rate (%)
12. Overall Population: Principal Secondary Efficacy Outcome (MI/Stroke/CV Death/Hospitalization) † Placebo + ASA * 17.9% Clopidogrel + ASA * 16.7% RRR: 7.7% [95% CI: 0.5%, 14.4%] P = 0.04 Cumulative event rate (%) 0 5 10 15 20 Months since randomization § 0 6 12 18 24 30 *All patients received ASA 75-162mg/day † First Occurrence of MI, Stroke, CV Death, or Hospitalization for UA, TIA, or Revascularization § The number of patients followed beyond 30 months decreases rapidly to zero and there are only 38 primary efficacy events that occurred beyond this time (23 clopidogrel and 15 placebo) Adapted with permission from Bhatt DL, et al. N Engl J Med. 2 006;354.
13. Overall Population: Secondary Efficacy Results *Intention to treat analysis † First occurrence of MI (fatal or not), stroke (fatal or not), cardiovascular death (including hemorrhagic death), or hospitalization for UA, TIA, or a revascularization procedure ‡ For UA, TIA, or revascularization Bhatt DL, et al. N Engl J Med. 2006;354. 0.02 0.90 (0.82, 0.98) 957 (12.3) 866 (11.1) Hospitalization ‡ 0.05 0.80 (0.65, 0.997) 185 (2.4) 149 (1.9) Stroke 0.10 0.82 (0.66, 1.04) 160 (2.1) 132 (1.7) Ischemic Stroke 0.48 0.92 (0.74, 1.16) 159 (2.0) 147 (1.9) Myocardial Infarction 0.68 1.04 (0.87, 1.25) 229 (2.9) 238 (3.1) Cardiovascular Mortality 0.90 0.99 (0.86, 1.14) 374 (4.8) 371 (4.8) All Cause Mortality 0.04 0.92 (0.86, 0.995) 1395 (17.9) 1301 (16.7) Principal Secondary Endpoint † P value RR (95% CI) Placebo + ASA (n=7801) Clopidogrel + ASA (n=7802) Endpoint* – N (%)
14. Overall Population: Safety Results *Adjudicated outcomes by intention to treat analysis ICH= Intracranial Hemorrhage Bhatt DL, et al. N Engl J Med. 2006;354. <0.001 1.62 (1.27, 2.10) 101 (1.3) 164 (2.1) GUSTO Moderate Bleeding 0.89 0.96 (0.56, 1.65) 27 (0.3) 26 (0.3) Primary ICH 0.17 1.53 (0.83, 2.82) 17 (0.2) 26 (0.3) Fatal Bleeding 0.09 1.25 (0.97, 1.61) 104 (1.3) 130 (1.7) GUSTO Severe Bleeding P value RR (95% CI) Placebo + ASA (n=7801) Clopidogrel + ASA (n=7802) Safety Outcome* – N (%)
15. Primary Efficacy Results (MI/Stroke/CV Death) by Pre-Specified Entry Category Population RR (95% CI) P value Qualifying CAD, CVD or PAD 0.88 (0.77, 0.998) 0.046 (n=12,153) Multiple Risk Factors 1.20 (0.91, 1.59) 0.20 (n=3284) Overall Population* 0.93 (0.83, 1.05) 0.22 (n=15,603) 0.6 0.8 1.4 1.2 Clopidogrel Better Placebo Better 1.6 0.4 * A statistical test for interaction showed marginally significant heterogeneity ( P = 0.045) in treatment response for these pre-specified subgroups of patients Bhatt DL, et al. N Engl J Med. 2006;354.
16. Primary Efficacy Results (MI/Stroke/CV Death)* by Category of Inclusion Criteria Population N RR (95% CI) P value Qualifying CV Disease 12,153 0.88 (0.77, 0.998) 0.046 Coronary 5,835 0.86 (0.71, 1.05) 0.13 Cerebrovascular 4,320 0.84 (0.69, 1.03) 0.09 PAD 2,838 0.87 (0.67, 1.13) 0.29 Multiple Risk Factors 3,284 1.20 (0.91, 1.59) 0.20 Overall Population 15,603 0.93 (0.83, 1.05) 0.22 0.6 0.8 1.4 1.2 Clopidogrel Better Placebo Better 1.6 0.4 * First occurrence of MI (fatal or not), Stroke (fatal or not), or CV Death Bhatt DL. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
17. Multiple Risk Factor Population: Secondary Efficacy Results *Intention to treat analysis † First occurrence of MI (fatal or not), stroke (fatal or not), cardiovascular death (including hemorrhagic death), or hospitalization for UA, TIA, or a revascularization procedure ‡ For UA, TIA, or revascularization Bhatt DL, et al. N Engl J Med. 2006;354. 0.55 0.93 (0.74, 1.18) 147 (9.0) 140 (8.4) Hospitalization ‡ 0.84 0.95 (0.60, 1.52) 36 (2.2) 35 (2.1) Stroke 0.73 0.91 (0.54, 1.54) 29 (1.8) 27 (1.6) Ischemic Stroke 0.45 1.19 (0.75, 1.89) 33 (2.0) 40 (2.4) Myocardial Infarction 0.01 1.74 (1.16, 2.62) 36 (2.2) 64 (3.9) Cardiovascular Mortality 0.04 1.41 (1.02, 1.95) 62 (3.8) 89 (5.4) All Cause Mortality 0.88 1.01 (0.84, 1.22) 216 (13.3) 224 (13.5) Principal Secondary Endpoint † P value RR (95% CI) Placebo + ASA (n=1625) Clopidogrel + ASA (n=1659) Endpoint* – N (%)
18. Multiple Risk Factor Population: Safety Results *Adjudicated outcomes by intention to treat analysis Bhatt DL, et al. N Engl J Med. 2006;354. 0.08 1.60 (0.95, 2.71) 22 (1.4) 36 (2.2) GUSTO Moderate Bleeding 0.81 1.14 (0.38, 3.39) 6 (0.4) 7 (0.4) Primary ICH 0.38 1.71 (0.50, 5.84) 5 (0. 2) 7 (0.4) Fatal Bleeding 0.07 1.67 (0.96, 2.88) 20 (1.2) 34 (2.0) GUSTO Severe Bleeding P value RR (95% CI) Placebo + ASA (n=1625) Clopidogrel + ASA (n=1659) Safety Outcome* – N (%)
19. Documented CV Disease Population: Safety Results *Adjudicated outcomes by Intention to treat analysis Bhatt DL, et al. N Engl J Med. 2006;354. <0.001 1.63 (1.23, 2.15) 79 (1.3) 128 (2.1) GUSTO Moderate Bleeding 0.65 0.87 (0.47, 1.60) 21 (0.3) 19 (0.3) Primary ICH 0.28 1.47 (0.73, 2.97) 13 (0.2) 19 (0.3) Fatal Bleeding 0.39 1.14 (0.85, 1.52) 84 (1.4) 95 (1.6) GUSTO Severe Bleeding P value RR (95% CI) Placebo + ASA (n=6091) Clopidogrel + ASA (n=6062) Safety Outcome* – N (%)
24. REACH Registry: >67,000 Patients From 5,473 Sites* in 44 Countries North America Latin America Eastern Europe Middle East Asia (incl. Japan) Australia 27,746 1,931 17,886 846 5,903 2,872 Western Europe 5,048 5,656 *Up to 15 patients/site (up to 20 in the US) Bhatt DL, et al. JAMA . 2006;295:180-189.
25.
26. 1-Year Results: Single vs Multiple and Overlapping Atherothrombotic Locations: The Example of CAD Rates adjusted for age and risk factors *TIA, unstable angina, other ischemic arterial event including worsening of PAD Steg PG. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga. (%)
27. Major Endpoints as a Function of Single vs Multiple and Overlapping Locations 1 p<0.05; 2 p<0.01; 3 p<0.001 (ref class: CAD alone) 1 p<0.05; 2 p<0.01; 3 p<0.001 (ref class: CAD + CVD) *TIA, unstable angina, other ischemic arterial event including worsening of PAD Steg PG. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga. Polyvascular disease Single arterial bed 26.9 (3) 7.4 4.0 1.8 3.6 (3) CAD + CVD + PAD 24.4 (1) 7.0 4.8 1.3 1.8 CVD + PAD 23.3 (3) 4.8 (3) 1.3 (3) 1.4 2.9 (2) CAD + PAD 20.0 6.4 3.7 1.6 2.0 CAD + CVD 22.0 6.0 3.1 1.5 2.4 Overall 18.2 (3) 10.0 (3) 13.3 12.8 CV death/MI/ stroke/ hospitalization 2.3 4.5 (3) 3.1 3.4 CV death/MI/stroke 0.6 3.5 (3) 0.9 1.5 Non-fatal stroke 1.0 0.5 (3) 1.4 1.2 Non-fatal MI 1.2 1.4 1.5 1.5 CV death PAD alone CVD alone CAD alone Overall
30. Study Design – First Randomization Moderate- high risk ACS Aspirin in all clopidogrel dosing and timing per local practice Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800) *Stratified by pre-angiography thienopyridine use or administration Stone GW, et al. Am Heart J . 2004;148:764-775. Angiography within 72h UFH or Enoxaparin + GP IIb/IIIa Bivalirudin + GP IIb/IIIa Bivalirudin alone R* Medical management PCI CABG
31. Study Design – Second Randomization Moderate- high risk ACS Angiography within 72h Aspirin in all clopidogrel dosing and timing per local practice Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800) Stone GW, et al. Am Heart J . 2004;148:764-775. Medical management PCI CABG Bivalirudin alone UFH or enoxaparin Routine upstream GPI in all pts GPI started in CCL for PCI only R Bivalirudin R Routine upstream GPI in all pts GPI started in CCL for PCI only
32. Primary Endpoint Measures (ITT) 11.7% 7.3% 5.7% 5.3% 11.8% 7.7% Net clinical outcome Ischemic composite Major bleeding 30 day events (%) UFH/Enoxaparin+GPI (N=4603) Bivalirudin+GPI (N=4604) P NI < 0.0001 P Sup = 0.93 P NI = 0.007 P Sup = 0.39 P NI = 0.0001 P Sup = 0.38 UFH/Enoxaparin + GPI vs Bivalirudin + GPI Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
33. Primary Endpoint Measures (ITT) 0 1 2 11.7% 11.8% 1.01 (0.90-1.12) <0.001 0.93 Risk ratio ±95% CI Primary endpoint Net clinical outcome Ischemic composite Major bleeding Bivalirudin + IIb/IIIa better UFH/Enox + IIb/IIIa better Bival + IIb/IIIa UFH/Enox + IIb/IIIa RR (95% CI) P value (noninferior) (superior) 7.3% 7.7% 1.07 (0.92-1.23) 0.015 0.39 5.7% 5.3% 0.93 (0.78-1.10) <0.001 0.38 Upper boundary noninferiority UFH/Enoxaparin + GPI vs Bivalirudin + GPI Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
34. Primary Endpoint Measures (ITT) 11.7% 7.3% 5.7% 3.0% 10.1% 7.8% Net clinical outcome Ischemic composite Major bleeding 30 day events (%) UFH/Enoxaparin+GPI (N=4603) Bivalirudin alone (N=4612) P NI <0.0001 P Sup = 0.015 P NI = 0.011 P Sup = 0.32 P NI <0.0001 P Sup <0.0001 UFH/Enoxaparin + GPI vs Bivalirudin Alone Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
35. Primary Endpoint Measures (ITT) Bivalirudin alone better UFH/Enox + IIb/IIIa better Risk ratio ±95% CI Primary endpoint Bival alone UFH/Enox + IIb/IIIa RR (95% CI) Net clinical outcome Ischemic composite Major bleeding Upper boundary non-inferiority 11.7% 10.1% 0.86 (0.77-0.97) <0.001 0.015 7.3% 7.8% 1.08 (0.93-1.24) 0.02 0.32 5.7% 3.0% 0.53 (0.43-0.65) <0.001 <0.001 P value (non inferior) (superior) UFH/Enoxaparin + GPI vs Bivalirudin Alone 0 1 2 Upper boundary noninferiority Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
36. Components of the Ischemic Composite 7.3% 1.3% 4.9% 2.3% 2.7% 2.4% 5.0% 7.7% 1.5% 1.6% 7.8% 5.4% Ischemic composite Death Myocardial infarction Unplanned revasc for ischemia 30 day events (%) UFH/Enox+GPI (N=4603) Bivalirudin+GPI (N=4604) Bivalirudin alone (N=4612) UFH/Enoxaparin + GPI vs Bivalirudin + GPI vs Bivalirudin Alone Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga. P Sup = 0.32 P Sup = 0.34 P Sup = 0.35 P Sup = 0.78
37. Major Bleeding Endpoints P Sup = 0.38 P Sup < 0.0001 P Sup = 0.31 P Sup < .001 UFH/Enoxaparin + GPI vs Bivalirudin + GPI vs Bivalirudin Alone 11.8% 5.7% 11.1% 5.3% 3.0% 9.1% All major bleeding Non-CABG major bleeding (primary endpoint) 30 day events (%) Heparin+GPI (N=4603) Bivalirudin+GPI (N=4604) Bivalirudin alone (N=4612) Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
38. Conclusions: Primary Results NI = noninferiority; Sup = superiority Stone G. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga. P Value Rate P Value Rate Rate Observed <0.001 Sup 3.0% 0.001 NI 5.3% 5.7% Major bleeding 0.011 NI 7.8% 0.007 NI 7.7% 7.3% Ischemic events 0.015 Sup 10.1% <0.001 NI 11.8% 11.7% Net clinical outcome Endpoint Bivalirudin alone Bivalirudin + GP IIb/IIIa UFH/Enox + GP IIb/IIIa
41. Protocol Design STEMI < 6 h Lytic eligible Lytic choice by MD (TNK, tPA, rPA, SK) UFH 60 U / kg bolus (4000 U) Inf 12 U / kg / h (1000 U / h) Duration: at least 48 h Cont’d at MD discretion ENOX < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) ≥ 75 y: No bolus SC 0.75 mg / kg q 12 h (Hosp DC) CrCl < 30: 1.0 mg / kg q 24 h Double-blind, double-dummy ASA Day 30 1 ° Efficacy Endpoint: Death or Nonfatal MI 1° Safety Endpoint: TIMI Major Hemorrhage Antman EM, et al. N Engl J Med . 2006;354.
42. Primary End Point (ITT) Death or Nonfatal MI Primary End Point (%) ENOX UFH Relative Risk 0.83 (0.77 to 0.90) P <0.001 Days after Randomization 9.9% 12.0% Lost to follow-up = 3 17% RRR Adapted with permission from Antman EM, et al. N Engl J Med . 2006;354.
43. Major Secondary End Point Death or Nonfatal MI or Urgent Revascularization (ITT) Secondary End Point (%) Days ENOX UFH 11.7% (1199) 14.5% (1479) 5.3% 6.1% RR 0.88 (0.79 to 0.98) P =0.02 48 h UFH ENOX 280 events 19% RRR RR 0.81 (0.75 to 0.87) P <0.001 12% RRR Adapted with permission from Antman EM, et al. N Engl J Med . 2006;354.
44. Death or Nonfatal MI – Day 30 Major Subgroups Adapted with permission from Antman EM, et al. N Engl J Med . 2006;354. > Median < Median Fibrin-specific Streptokinase Prior MI No Prior MI DM No DM Other Anterior 0.5 1 2 PRIOR MI OVERALL DIABETES FIBRINOLYTIC INFARCT LOCATION ENOX Better UFH Better Relative Risk TIME TO Rx 20,479 11 23 17 21 17 20 13 18 23 12 17 Reduction In Risk (%) > 75 < 75 AGE (y) 20 6 Female Male SEX 18 16 All Interaction Tests P = NS P < 0.0001
45. Bleeding Endpoints (TIMI) 30 Days UFH ENOX % Events Major Bleed (fatal + nonfatal) ICH ARD 0.7% RR 1.53 P<0.001 ARD 0.1% RR 1.27 P = 0.14 Nonfatal Major Bleed ARD 0.4% RR 1.39 P = 0.014 Antman EM, et al. N Engl J Med . 2006;354.
46. Net Clinical Benefit at 30 Days 1 1.25 0.9 0.8 Death or Nonfatal MI or Nonfatal ICH Death or Nonfatal MI or Nonfatal Major Bleed Death or Nonfatal MI or Nonfatal Disabl. Stroke ENOX Better UFH Better RR UFH (%) ENOX (%) RRR (%) 12.3 10.1 18 12.8 11.0 14 12.2 10.1 17 Prespecified Definitions P <0.001 P <0.001 P <0.001 Antman EM, et al. N Engl J Med . 2006;354.
47. Clinical Implication A strategy of enoxaparin is preferable to the current standard of unfractionated heparin as the antithrombin to support fibrinolysis, the most common form of reperfusion for STEMI used worldwide.
60. ISAR REACT 2: Cumulative Incidence of Death, MI, or Urgent TVR Adapted with permission from Kastrati A, et al. JAMA . 2006;295. Published online March 13, 2006. 20 15 10 5 0 0 5 10 15 20 25 30 Days After Randomization Cumulative Rate of Primary End Point, % Placebo Group Abciximab Group Log-Rank P =.03
61. ISAR REACT 2: 30-Day Ischemic Events Abbreviations: CI, confidence interval; MI, myocardial infarction; RR, relative risk. Adapted with permission from Kastrati A, et al. JAMA . 2006;295. Published online March 13, 2006. No. (%) 0.64 (0.25-1.63) 11 (1.1) 7 (0.7) PCI 2.99 (0.24-157) 1 (0.1) 3 (0.3) Aortocoronary bypass surgery 0.83 (0.36-1.92) 12 (1.2) 10 (1.0) Urgent target vessel revascularization 0.78 (0.36-1.72) 14 (1.4) 11 (1.1) Q-wave MI 0.77 (0.59-1.02) 106 (10.5) 82 (8.1) MI 0.69 (0.32-1.47) 16 (1.6) 11 (1.1) Death 0.75 (0.57-0.97) 116 (11.5) 87 (8.6) Death or MI 0.75 (0.58-0.97) 120 (11.9) 90 (8.9) Death, MI, or urgent target vessel revascularization RR (95% CI) Placebo (n=1010) Abciximab (n=1012) Event
62. ISAR REACT 2: Cumulative Incidence of Death, MI, or Urgent TVR in Subsets With and Without Elevated Troponin Levels (>0.03 µg/L) Adapted with permission from Kastrati A, et al. JAMA . 2006;295. Published online March 13, 2006. 20 15 10 5 0 0 5 10 15 20 25 30 Days After Randomization Cumulative Rate of Primary End Point, % Placebo Group Abciximab Group Troponin >0.03 µg/L Log-Rank P = .02 Troponin < 0.03 µg/L Log-Rank P = .98
63. ISAR REACT 2: 30-Day Incidence and Relative Risk of Death, MI, or Urgent TVR in Subgroups Error bars indicate 95% confidence intervals. Adapted with permission from Kastrati A, et al. JAMA . 2006;295. Published online March 13, 2006. Abciximab Placebo All Participants 90/1012 (8.9) 120/1010 (11.9) Troponin Level >0.03 µg/L 67/513 (13.1) 98/536 (18.3) ≤ 0.03 µg/L 23/499 (4.6) 22/474 (4.6) Clopidogrel Pretreatment Duration >3 h 27/475 (5.7) 35/461 (7.6) ≤ 3 h 63/537 (11.7) 85/549 (15.5) Diabetes Yes 26/252 (10.3) 32/284 (11.3) No 64/760 (8.4) 88/726 (12.1) Primary End Point, No. of Events/Total No. (%) 0.4 1 2 Relative Risk
64. ISAR-REACT 2 Trial: Secondary Endpoint In-hospital Major and Minor Bleeding (%) p=NS Kastrati A, et al. JAMA . 2006;295. Published online March 13, 2006.
69. ASTEROID: Example of Regression of Atherosclerosis in a Patient in the Trial Adapted with permission from Nissen S, et al. JAMA . 2006;295. Published online March 13, 2006.
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75. Relationship Between Mean LDL-C Levels and Median Change in % Atheroma Volume for Several Intravascular Ultrasound Trials Adapted with permission from Nissen S, et al. JAMA . 2006;295. Published online March 13, 2006. REVERSAL Pravastatin CAMELOT Placebo A-Plus Placebo REVERSAL Atorvastatin ASTEROID Rosuvastatin r 2 = 0.97 P <.001
80. Progress Checklist: Immediate Goals Circulate discharge plan and other tools to all cardiology, ED, and CV nursing staff for comments Circulate pathways to all cardiology, ED, and CV nursing staff for comments Develop draft pathways Assemble team and set up meeting of working group
81. Progress Checklist: Short-term Goals/Activities Grand rounds/conference: Cardiology/IM Grand rounds/conference: Emergency Dept. Grand rounds/conference: Nursing Circulate memo Launch critical pathways Finalize critical pathways
82. Progress Checklist: Long-term Goals/Activities NRMI AHA Get With The Guidelines ACC National Cardiovascular Data Registry CRUSADE GRACE REACH Other Monitor data: which registry?
84. Concluding Remarks Gregg C. Fonarow, MD Next program: Wednesday, April 19, 2006 - 3PM ET (12N PT) Topic: Preliminary Findings From the REACH Registry Faculty: Gregg C. Fonarow, MD