This 3-sentence summary provides the key details about the PEGASUS-TIMI 54 trial:
The PEGASUS-TIMI 54 trial investigated whether adding ticagrelor to low-dose aspirin would reduce cardiovascular events in patients with a history of heart attack 1-3 years prior, randomizing over 21,000 patients to ticagrelor 90mg twice daily, ticagrelor 60mg twice daily, or placebo on a background of aspirin. The trial found that both doses of ticagrelor significantly reduced the primary composite endpoint of cardiovascular death, heart attack, or stroke compared to placebo with an increased risk of major bleeding, demonstrating the benefit of extended dual antiplatelet therapy beyond
Ticagrelor in acute myocardial infarctionVasif Mayan
Potential benefits of dual antiplatelet therapy beyond 1 year after an MI has not been studied
Patients with MI are at increased risk of RECURRENT ISCHAEMIC EVENTS
Intensive secondary prevention is theoretically beneficial
Finding an ideal drug with best risk-benefit ratio is a challenge
TICAGRELOR
--- Direct acting
Not a pro-drug; does not require metabolic activation
Rapid onset of inhibitory effect on the P2Y12 receptor
Greater inhibition of platelet aggregation than clopidogrel
--- Reversibly bound
Degree of inhibition reflects plasma concentration
Faster offset of effect than clopidogrel
Functional recovery of circulating platelets within ~48 hours
PLATO trial
PEGASUS TIMI trial
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/
http://www.theheart.org/web_slides/1144191.do
A randomized to prasugrel or clopidogrel study on TRITON-TIMI 38 with patients who have moderate- to high-risk ACS.
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
Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients
with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal
treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from ei ther shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor
monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of
treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk
scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores
have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms
of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function
testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint
on the use of different risk stratification methods alongside clinical judgement in current clinical practice.
Dyslipidemia and CVS by Mohit Soni and Chandan KumarOlgaGoryacheva4
My students Mohit Soni and Chandan Kumar had presented this topic in our 22nd Student Scientific Society Conference in the department of Propaedeutic of Internal Diseases No.2
Antiplatelet therapy there is a gap between guidelines and implementationA.Salam Sharif
platelets play an important role in cardiovascular diseases, the final event leading to ACS is a spontaneous atherosclerotic plaques which initiates a platelet response with platelet adhesion to vascular wall with activation and agregation and finally clot formation with clinical sequences od CV deaths, MI and myocardial ischemia and arrhythmias, so atiplatelet therapy is crucial in treatment of ACS, in the topic I review the traditional agents and new agents , focusing on guidelines and real world of their cinical uses .
Ticagrelor in acute myocardial infarctionVasif Mayan
Potential benefits of dual antiplatelet therapy beyond 1 year after an MI has not been studied
Patients with MI are at increased risk of RECURRENT ISCHAEMIC EVENTS
Intensive secondary prevention is theoretically beneficial
Finding an ideal drug with best risk-benefit ratio is a challenge
TICAGRELOR
--- Direct acting
Not a pro-drug; does not require metabolic activation
Rapid onset of inhibitory effect on the P2Y12 receptor
Greater inhibition of platelet aggregation than clopidogrel
--- Reversibly bound
Degree of inhibition reflects plasma concentration
Faster offset of effect than clopidogrel
Functional recovery of circulating platelets within ~48 hours
PLATO trial
PEGASUS TIMI trial
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/
http://www.theheart.org/web_slides/1144191.do
A randomized to prasugrel or clopidogrel study on TRITON-TIMI 38 with patients who have moderate- to high-risk ACS.
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
Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients
with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal
treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from ei ther shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor
monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of
treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk
scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores
have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms
of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function
testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint
on the use of different risk stratification methods alongside clinical judgement in current clinical practice.
Dyslipidemia and CVS by Mohit Soni and Chandan KumarOlgaGoryacheva4
My students Mohit Soni and Chandan Kumar had presented this topic in our 22nd Student Scientific Society Conference in the department of Propaedeutic of Internal Diseases No.2
Antiplatelet therapy there is a gap between guidelines and implementationA.Salam Sharif
platelets play an important role in cardiovascular diseases, the final event leading to ACS is a spontaneous atherosclerotic plaques which initiates a platelet response with platelet adhesion to vascular wall with activation and agregation and finally clot formation with clinical sequences od CV deaths, MI and myocardial ischemia and arrhythmias, so atiplatelet therapy is crucial in treatment of ACS, in the topic I review the traditional agents and new agents , focusing on guidelines and real world of their cinical uses .
A comprehensive approach to Atrial Fibrillation. Everything you need to know about Atrial fibrillation. Including recent 2014 AHA guidelines of management.
Dr. mahajna muhammad MD
sackler faculty of medicine
Tel-Aviv Uni.
The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context.
Ohio State's ASH Review 2017 - Benign HematologyOSUCCC - James
Spero R. Cataland, MD
Professor of Clinical Internal Medicine
The Ohio State University Comprehensive Cancer Center -
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Introduction: Recent times have witnessed almost half, or sometimes more cardiac surgical procedures are performed in patients above 75 years of age. Traditionally, the EuroSCORE II and STS risk scoring systems have been widely used across the globe. Extensive reviews have shown that EuroSCORE II probably overestimates the perioperative risk at lower score levels while the STS score tends to underestimate the risk.
Frailty is a broad term that encircles aspects of nutrition, lack of agility, inactivity, lack of strength and wasting; and is seen in 25-50% of elderly patients. It has been defined as a geriatric syndrome reflecting a state of reduced physiological reserve and increased vulnerability to poor resolution of homeostasis after a stressor event. Conversely, pre-frailty, which is potentially reversible, is associated with higher risk of older adults developing cardiovascular disease.
Frailty assessment includes a variety of physical and cognitive tests, functional assessments and evaluating nutritional status. Literature has highlighted what is referred to as the ‘obesity paradox’, meaning obese patients with heart failure fair better than leaner patients, possibly because they have more metabolic reserve and also because weight loss in itself is a risk factor for frailty.
Patient Selection: To comprehensively assess a patient, factors that describe the biological status of the patient should be incorporated. There are various methods of assessment and modified Fried criteria or comprehensive assessment of frailty are a couple of systems commonly used.
Conclusion: Systematic reviews have shown that frail patients have higher chance of mortality, major adverse cardiac and cerebrovascular events and functional decline after cardiac surgery. A holistic assessment not only categorises patients into the apt risk category and hence match goals and treatments; but also, will pick up patients with pre-frailty who will benefit from multidisciplinary intervention and be better prepared for the intervention.
Clinical trials are medical research studies conducted on human subjects. The human subjects are assigned to one or more interventions, and the investigators evaluate the effects of those interventions. The progress and results of clinical trials are analyzed statistically. The aim of statistical analysis in a randomized clinical trial is the comparison of the benefit of treatment compared to control or other groups. This enables medical researchers to analyze the entirety of primary and secondary-use patient data records for unparalleled epidemiological and clinical data. One of the main components of the analysis is the statistical analysis plan (SAP). This plan ensures that the analyses to evaluate all planned study hypotheses. So this explanation in presentation talk about : How to do clinical trials.
Fundación EPIC _ Tratamiento anticoagulante/antiagregante al alta en TAVIFundacion EPIC
Presentación de la ponencia "Tratamiento anticoagulante/antiagregante al alta en TAVI" Por el Dr. Ferreiro en los Diálogos EPIC_Retos Clínicos en Válvulas Transcatéter/ Clinical Challenges in TAVR today, el 10 de Mayo de 2018 en Barcelona (España)
Современное лечение ВИЧ: лечение ВИЧ у женщин.2017/Contemporary Management of...hivlifeinfo
In this downloadable slideset, Kathleen E. Squires, MD, and Program Director Joseph J. Eron, Jr., MD, review key data and optimal strategies in caring for HIV-infected women, including ART safety and efficacy in women, reproductive health management, ART and pregnancy, and preventing HIV infection in women.
Format: Microsoft PowerPoint (.ppt)
File size: 1.59 MB
Date posted: 4/25/2017
Heart summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013
Contemporary Management of HIV. New Data From IDWeek 2018 and Other Fall 2018...hivlifeinfo
Contemporary Management of HIV. New Data From IDWeek 2018 and Other Fall 2018 HIV Conferences
Format: Microsoft PowerPoint (.ppt)
File Size: 690 KB
Released: December 5, 2018
My talk in April 2015 Malaysia on Best Practices and Resuscitation Workflow. The new 2015 resuscitation guidelines is expected to be released in Oct 2015.
What is the place of CT coronary angiography in ED chest pain?kellyam18
CT coronary angiography is a relatively new modality for identifying coronary artery disease. What is its place in ED chest pain assessment. See the evidence -and the evidence gaps- and judge for yourself where it might fit!
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.
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.
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.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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
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
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.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
1. Prevention of Cardiovascular Events
in Patients With Prior Heart Attack Using
Ticagrelor Compared to Placebo on a
Background of Aspirin
Marc S. Sabatine, MD, MPH
on behalf of the PEGASUS-TIMI 54
Executive & Steering Committees and Investigators
NCT00526474
2. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Background
• Current guidelines recommend adding a P2Y12
receptor antagonist to aspirin only for the first year
after an acute coronary syndrome (ACS)
• However, several lines of evidence suggest more
prolonged therapy may be beneficial in Pts w/ prior MI
– Landmark analyses from 1-year ACS trials of P2Y12 antag
– Post-hoc MI subgroup analysis from CHARISMA
• Ticagrelor is a potent, reversibly-binding, direct-
acting P2Y12 antagonist with established efficacy for
the first year after an ACS
3. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Hypothesis
The addition of ticagrelor to standard therapy
(including low-dose aspirin) would reduce the
incidence of major adverse cardiovascular
events during long-term follow-up
in patients with a history of MI
4. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Trial Organization
TIMI Study Group
Eugene Braunwald (Chair) Marc S. Sabatine (PI)
Marc P. Bonaca (Co-PI) Stephen D. Wiviott (CEC Chair)
S Morin & P Fish (Operations) SA Murphy & Kelly Im (Statistics)
Executive Cmte
Eugene Braunwald (Chair) Marc S. Sabatine
Deepak L. Bhatt Marc Cohen
Ph. Gabriel Steg Robert Storey
Sponsor: AstraZeneca
Peter Held Eva Jensen
Per Johanson Ann Maxe Ahlbom
Barbro Boberg Olof Bengtsson
Independent Data Monitoring Cmte
Jeffrey L. Anderson (Chair) Terje R. Pedersen
Freek W.A.Verheugt Harvey D. White
David L. DeMets
5. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Argentina Germany Russia
R. Diaz/E Paolasso C Hamm M Ruda
Australia Hungary S. Africa
P Aylward R Kiss A Dalby
Belgium Italy S. Korea
F Van der Werf D Ardissino K Seung
Brazil Japan Slovakia
J Nicolau S Goto G Kamensky
Bulgaria Netherlands Spain
A Goudev T Oude Ophuis J Lopez-Sendon
Canada Norway Sweden
P Theroux F Kontny M Dellborg
Chile Peru Turkey
R Corbalan F Medina S Guneri
China Philippines UK
D Hu MT Abola R Storey
Colombia Poland Ukraine
D Isaza A Budaj A Parkhomenko
Czech Republic Romania USA
J Spinar D Dimulescu Bonaca/Bhatt/Cohen
France
G Montalescot/PG Steg
Steering Committee
6. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Stable pts with history of MI 1-3 yrs prior
+ ≥1 additional atherothrombosis risk factor
Ticagrelor
90 mg bid
Placebo
RANDOMIZED
DOUBLE BLIND
Follow-up Visits
Q4 mos for 1st yr, then Q6 mos
Planned treatment with ASA 75 – 150 mg/d &
Standard background care
Minimum 1 year follow-up
Event-driven trial
Ticagrelor
60 mg bid
Trial Design
Bonaca MP et al. Am Heart J 2014;167:437-44
7. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Key Inclusion & Exclusion Criteria
KEY INCLUSION
• Age ≥50 years
• At least 1 of the following:
– Age ≥65 years
– Diabetes requiring medication
– 2nd prior MI (>1 year ago)
– Multivessel CAD
– CrCl <60 mL/min
• Tolerating ASA and able to be
dosed at 75-150 mg/d
KEY EXCLUSION
• Planned use of P2Y12 antagonist,
dipyridamole, cilostazol, or anticoag
• Bleeding disorder
• History of ischemic stroke, ICH, CNS
tumor or vascular abnormality
• Recent GI bleed or major surgery
• At risk for bradycardia
• Dialysis or severe liver disease
Bonaca MP et al. Am Heart J 2014;167:437-44
8. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Endpoints
• Efficacy: hierarchical testing
– Primary: cardiovascular (CV) death, MI, or stroke
– Secondary: CV death; all-cause mortality
– Prespecified exploratory: substituting coronary for CV death;
other individual coronary and cerebrovascular ischemic
outcomes; pooling ticagrelor doses
• Safety
– Primary: TIMI Major Bleeding
– Other: intracranial hemorrhage (ICH), fatal bleeding
– AEs/SAEs
• TIMI Clinical Events Committee (CEC)
– Adjudicated all efficacy endpoints & bleeding events
– Members unaware of treatment assignments
Bonaca MP et al. Am Heart J 2014;167:437-44
9. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Poland: 1399Sweden: 507
Canada:
1306
United States
2601
U.K.: 647
Netherlands: 1560
Belgium: 431
Germany: 924
France: 333
Spain: 535
Czech Rep: 870
Italy: 392
South Africa:
473
Australia: 327
Japan: 903Hungary: 831
Bulgaria: 447
China: 383
S Korea: 506
Philippines: 250
Colombia: 528
Chile: 322
Argentina: 499
Brazil: 864
Peru: 245
Romania: 404
Slovakia: 475
Russia: 1061Ukraine: 623
Turkey: 180
Norway: 336
21,162 patients randomized at 1161 sites in 31 countries between 10/2010 – 5/2013
Global Enrollment
10. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Randomized 21,162 patients
Ticagrelor
90 mg bid
(N=7050)
Placebo
(N=7067)
Ticagrelor
60 mg bid
(N=7045)
Follow-Up
Premature perm.
drug discontinuation
12%/yr 11%/yr 8%/yr
Withdrew consent 0.7% total 0.7% total 0.7% total
Lost to follow-up 3 patients 6 patients 1 patient
Follow-up median 33 months (IQR 28-37)
Minimum 16 months, maximum 47 months
Ascertainment for primary endpoint was complete
for 99% of potential patient-years of follow up
11. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Baseline Characteristics
Characteristic Value
Age – yr, mean (SD) 65 (8)
Female 24
Hypertension 78
Hypercholesterolemia 77
Current smoker 17
Diabetes mellitus 32
Estimated GFR <60 mL/min/1.73m2 23
History of PCI 83
Multivessel coronary disease 59
History of more than 1 prior MI 17
No difference between treatment arms.
Values for categorical variables are %.
12. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Baseline Characteristics
Characteristic Value
Qualifying Event
Years from MI – median (IQR) 1.7 (1.2 – 2.3)
History of STEMI 53
History of NSTEMI 41
MI type unknown 6
No difference between treatment arms.
Values for categorical variables are %.
0
10
20
30
40
50
<3 3-4 4-5 5-6 >6
%ofpatients
Years from qualifying MI to end of follow-up
13. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Baseline Characteristics
Characteristic Value
Qualifying Event
Years from MI – median (IQR) 1.7 (1.2 – 2.3)
History of STEMI 53
History of NSTEMI 41
MI type unknown 6
Medications at enrollment
Aspirin (any dose) 99.9
Dose 75-100 mg/d 97.3
Statin 93
Beta-blocker 82
ACEI or ARB 80
No difference between treatment arms.
Values for categorical variables are %.
14. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Months from Randomization
Ticagrelor 60 mg
HR 0.84 (95% CI 0.74 – 0.95)
P=0.004
CVDeath,MI,orStroke(%)
3 6 9 120 15 18 21 24 27 30 33 36
Ticagrelor 90 mg
HR 0.85 (95% CI 0.75 – 0.96)
P=0.008
Placebo (9.0%)
Ticagrelor 90 (7.8%)
Ticagrelor 60 (7.8%)
Primary Endpoint
6
5
4
3
10
9
8
7
2
1
0
N = 21,162
Median follow-up 33 months
15. An Academic Research Organization of
Brigham and Women’s Hospital and Harvard Medical School
Components of Primary Endpoint
0.85 (0.75-0.96) 0.008
0.84 (0.74-0.95) 0.004
0.84 (0.76-0.94) 0.001
CV Death, MI, or Stroke
(1558 events)
HR (95% CI) P value
10.80.60.4 1.25 1.67
Ticagrelor better Placebo better
Endpoint
Ticagrelor 60 mg
Ticagrelor 90 mg
Pooled
CV Death
(566 events)
0.87 (0.71-1.06) 0.15
0.83 (0.68-1.01) 0.07
0.85 (0.71-1.00) 0.06
Myocardial Infarction
(898 events)
0.81 (0.69-0.95) 0.01
0.84 (0.72-0.98) 0.03
0.83 (0.72-0.95) 0.005
Stroke
(313 events)
0.82 (0.63-1.07) 0.14
0.75 (0.57-0.98) 0.03
0.78 (0.62-0.98) 0.03
16. An Academic Research Organization of
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Other Efficacy Outcomes
Outcome
Ticagrelor
90 mg bid
(N=7050)
Ticagrelor
60 mg bid
(N=7045)
Placebo
(N=7067)
Ticagrelor 90
vs Placebo
p-value
Ticagrelor 60
vs Placebo
p-value
Coronary Death,
MI, or Stroke
7.0 7.1 8.3
HR 0.82
P=0.002
HR 0.83
P=0.003
Coronary Death
or MI
5.6 5.8 6.7
HR 0.81
P=0.004
HR 0.84
P=0.01
Coronary Death 1.5 1.7 2.1
HR 0.73
P=0.02
HR 0.80
P=0.09
Death from any
cause
5.2 4.7 5.2
HR 1.00
P=0.99
HR 0.89
P=0.14
3-yr KM rate (%)
17. An Academic Research Organization of
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Subgroup Pts
All Patients 21,162
Age at Randomization
Age < 75 18,079
Age ≥ 75 3,083
Sex
Female 5,060
Male 16,102
Qualifying MI
NSTEMI 8,583
STEMI 11,329
Unknown 1,223
Time from Qualifying MI
< 2 years 12,980
≥ 2 years 8,155
Region
North America 3,907
South America 2,458
Europe 12,428
Asia 2,369
Efficacy for 1° EP in Subgroups
Placebo better
0.4 0.5 0.85 1 1.5 2.0 2.5
Hazard Ratio (95% CI)
Ticagrelor 90 mg vs Placebo
Hazard Ratio (95% CI)
Ticagrelor 60 mg vs Placebo
Ticagrelor 90 mg better
All P values for heterogeneity >0.05 0.4 0.5 0.84 1 1.5 2.0 2.5
Placebo betterTicagrelor 60 mg better
18. An Academic Research Organization of
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Bleeding
2.6
1.3
0.6 0.6
0.1
2.3
1.2
0.7 0.6
0.3
1.1
0.4
0.6 0.5
0.3
0
1
2
3
4
5
TIMI Major TIMI Minor Fatal bleeding or
ICH
ICH Fatal Bleeding
3-YearKMEventRate(%)
Ticagrelor 90 mg
Ticagrelor 60 mg
PlaceboP<0.001
P<0.001
P=NS P=NS P=NS
Ticag 60: HR 2.32 (1.68-3.21)
Ticag 90: HR 2.69 (1.96-3.70)
19. An Academic Research Organization of
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Other Adverse Events
Adverse Event
Ticagrelor
90 mg bid
(N=6988)
Ticagrelor
60 mg bid
(N=6958)
Placebo
(N=6996)
Ticagrelor 90
vs Placebo
p-value
Ticagrelor 60
vs Placebo
p-value
Dyspnea AE 18.9 15.8 6.4 P<0.001 P<0.001
Leading to
study drug d/c
6.5 4.6 0.8 P<0.001 P<0.001
Severe 1.2 0.6 0.2 P<0.001 P<0.001
Bradyarrhythmia 2.0 2.3 2.0 P=0.31 P=0.10
Gout 2.3 2.0 1.5 P<0.001 P=0.01
3-yr KM rate (%)
20. An Academic Research Organization of
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Summary
• Adding ticagrelor to low-dose aspirin in stable
patients with a history of MI reduced the risk of CV
death, MI or stroke
• The benefit of ticagrelor was consistent
– For both fatal & non-fatal components of primary endpoint
– Over the duration of treatment
– Among major clinical subgroups
• Ticagrelor increased the risk of TIMI major bleeding,
but not fatal bleeding or ICH
• The two doses of ticagrelor had similar overall
efficacy, but bleeding and other side effects tended
to be less frequent with 60 mg bid dose
21. An Academic Research Organization of
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Conclusion
Long-term dual antiplatelet therapy with
low-dose aspirin and ticagrelor should
be considered in appropriate patients
with a myocardial infarction.