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
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.
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
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.
Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence.Polypill therapy significantly improved adherence, SBP and LDL-cholesterol in high risk patients compared with usual care, especially among those who were under-treated at baseline.
What are anti-coagulants?
What are the difference between antiplatelet, anticoagulants and thrombolytics?
Coagulation cascade
Virchows Triad
Classification of anti-coagulants?
Indications of anti-coagulants?
Mechanism and site of action of different anti-coagulants?
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence.Polypill therapy significantly improved adherence, SBP and LDL-cholesterol in high risk patients compared with usual care, especially among those who were under-treated at baseline.
What are anti-coagulants?
What are the difference between antiplatelet, anticoagulants and thrombolytics?
Coagulation cascade
Virchows Triad
Classification of anti-coagulants?
Indications of anti-coagulants?
Mechanism and site of action of different anti-coagulants?
Secondary Prevention after ACS: Focused on Anticoagulant TherapyPERKI Pekanbaru
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Strategy to Go for Goal in Dyslipidemia with Acute Coronary Syndrome PatientsPERKI Pekanbaru
Dr. A. Fauzi Yahya, SpJP (K), FIHA, FAsCC. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Dr. Nathania Marliani Kristanti, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Prof. DR. Dr. Rochmad Romdoni, SpJP(K), FINASIM, FIHA, FAsCC. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com
Diabetes and acute coronary syndrome
Diabetic patients as compared to non diabetics withacute cornary syndrome (ACS) at 2 years showed a
1.8 fold increase in cardiovascular deaths
1.4 fold increase in myocardial infarctions (MI)
www.srisriholistichospitals.com
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.
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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.
2. The Standard Dual Antiplatelet
Therapy for ACS
Clopidogrel : loading dose 300 mg, followed
by 75 mg daily
ASA: 160 mg non-enteric chewed tablet,
followed by 80 mg daily
3. Trial & population Comparison Primary Endpoint Bleeding
CURE (2001)
NSTE-ACS patients
n = 12,562
Clopidogrel 75 mg
(300 mg loading)
vs. placebo
CV death, MI, CVA
Clopidogrel 9.3%
Placebo 11.4%
(P < 0.001)
ARR 2.1%;
RRR 20%; NNT 48
Major bleeding*
Clopidogrel 3.7%
Placebo 2.7%
(P = 0.001)
NNH: 100
PCI Cure (2001)
NSTE-ACS undergoing
PCI
n = 2,658
Like CURE (after PCI
clopidogrel in both
groups for 1 month)
CV death, MI, or
urgent TVR in
30 days
Clopidogrel 4.5%
Placebo 6.4%
ARR 1.9%;
RRR 30%; NNT 53
Major bleeding*
Clopidogrel 2.7%
Placebo 2.5%
(P = 0.69
CURRENT OASIS 7 (2010)
NSTE-ACS - 63%
STEMI - 37%
n = 25,086
Clopidogrel double
dose
(600 mg loading, 150
mg day 2–7, then 75
mg) vs. standard dose
75 mg (150 mg
loading)
CV death, MI, CVA
(at 30 days)
Double 4.2%
Standard 4.4%
(P = 0.30)
Major bleeding
Double 2.5%
Standard 2.0%
(P = 0.01)
NNH: 200
Clopidogrel Trials
Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
* CURE Definition
4. Potential Limitations of
Clopidogrel
Moderate overall levels of platelet inhibition
Average IPA ~50%
High variability response within a population
4-34% with very low levels of platelet inhibition
Slow onset of antiplatelet effect
Requiring 300 – 600 mg loading doses in acute
phase
Gurbel et al. Circulation 2009;120:2577-2585
O’ Donoghue M. Wiviott SD . Circulation 2006;114:e600-e606
5. Inhibition of ADP-Induced Platelet Function Following 600mg Clopidogrel in 1,001 patients
Hochholzer W. Circulation 2005;111: 2560-2564
Variability in Clopidogrel
Responsiveness
6. Angiolillo DJ & Ueno M. JACC: Cardiology Interventions 2011;4 (4):411–414
8. Ticagrelor is a cyclo-pentyl-
triazolo-pyrimidine (CPTP)
OH
OH
O
OH
N
F
S
N
H
N
N
N
N
F
• Direct-acting
– Not a pro drug: does not require metabolic activation
– Rapid onset of inhibitory effect on the P2Y12 receptor than clopidogrel
• Reversibly bound
– Faster offset than clopidogrel
– Functional recovery of circulating platelets within ~ 48 hours
Ticagrelor
Deeks ED. Drugs 2011;71(7):909-933
Husted S. Van Giezen JJJ. Cardiovascular Therapeutics 2009;27:259-274
9. Adapted from Schomig A. N Engl J Med. 2009;361:1108–1111.
Ticagrelor:
Does NOT require metabolic activation to
become active drug
Clopidogrel:
A prodrug; requires metabolism to
become active drug
CYP-dependent
oxidation
CYP1A2
CYP2B6
CYP2C19
CYP-dependent
oxidation
CYP2C19
CYP3A4/5
CYP2B6
Active compound
Intermediate metabolite
Prodrug
Ticagrelor
Clopidogrel
Binding
P2Y12
Ticagrelor: Does Not Require Hepatic
Metabolism for Activation
Platelet
10. Ticagrelor P2Y12 receptor
binding
ADP, adenosine diphosphate
Adapted from Husted S. Van Giezen JJJ. Cardiovascular Therapeutics 2009;27:259-274
ADP
P2Y12 receptor ADP binds and activates
the receptor
Conformational change
and signalling
Ticagrelor binds away
from ADP pocket
ADP can bind reversibly
but no conformational
change or signalling
Receptor remains intact
upon dissociation
14. PLATO Study
PLATO Study2:
• 43 countries
• 862 sites
• 18,624 patients
43 countries862 sites
PLATO study tested the hypothesis that…
ticagrelor will result in a lower risk of recurrent thrombotic events in a broad
patient population with ACS as compared to clopidogrel and this would be
achieved with a clinically acceptable bleeding rate and overall safety profile1
18,624 patients
1. James S et al. Am Heart J 2009;157: 599 – 605
2. Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
15. PLATO: Study Population
ACS Patient
STEMI
Primary PCI
No Reperf
Fibrinolytic Rx
UA/NSTEMI
Initial Invasive
Management
PCI
No revascularisation
CABG
Initial Non-Invasive
Management
PCI
CABG
No revascularisation
Only STEMI patients
intended for primary PCI
included
Adapted from James S, et al. Am Heart J. 2009;157:599–605.
16. 180-mg loading dose
Ticagrelor (n=9,333)
*STEMI patients scheduled for primary PCI were randomised; however, they may not have received PCI.
†A loading dose of 300-mg clopidogrel was permitted in patients not previously treated with clopidogrel,
with an additional 300 mg allowed at the discretion of the investigator.
‡The PLATO study expanded the definition of major bleeding to be more inclusive compared with
previous studies in ACS patients. The primary safety endpoint was the first occurrence of any major
bleeding event.
90 mg bid + ASA maintenance dose
300-mg loading dose† 75 mg qd + ASA maintenance dose
Clopidogrel (n=9,291)
Primary efficacy
endpoint:
Composite of CV
death, MI (excluding
silent MI), or stroke
Primary safety
endpoint:
Total PLATO major
bleeding‡
N=18,624
Patients with ACS
(UA, NSTEMI, or
STEMI*)
<24h Month 1 Month 3 Month 6 Month 9 Month 12Screening
Visit 2 Visit 3 Visit 4 Visit 5 Visit 6
Initial Treatment approaches
• Medically managed (n=5,216 — 28.0%)
• Invasively managed (n=13,408 — 72.0%)
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
James S, et al. Am Heart J. 2009;157:599–605.
Randomisation
• All patients were hospitalised with symptom onset <24 hours
• Patients could be taking clopidogrel at time of randomisation
PLATO: Study Design
17. PLATO Main: Inclusion Criteria
• Hospitalisation for STEMI or NSTEMI/UA ACS, with
onset during previous 24 hours
• With STEMI, the following 2 inclusion criteria were
required
– Persistent ST elevation of at least 0.1 mV in ≥2
contiguous leads or new LBBB
– Primary PCI planned
James S, et al. Am Heart J. 2009;157:599–605.
18. PLATO Main: Inclusion Criteria
• With NSTEMI, at least 2 of the following 3 were required
– ST changes on ECG indicating ischaemia
– Positive biomarker indicating myocardial necrosis
– One of the following risk indicators
• ≥60 years of age
• Previous MI or CABG
• CAD with ≥50% stenosis in ≥2 vessels
• Previous ischaemic stroke, TIA, carotid stenosis (≥50%), or
cerebral revascularisation
• Diabetes mellitus
• Peripheral artery disease
• Chronic renal dysfunction (creatinine clearance <60 mL/min)
James S, et al. Am Heart J. 2009;157:599–605.
19. PLATO Main: Key Exclusion Criteria
• Contraindication to clopidogrel
• Fibrinolytic therapy within 24 hours
• Oral anticoagulation therapy that cannot be stopped
• ACS event was a complication of previous PCI
• PCI after index event (initial clinical signs and symptoms)
and before first study dose
• Increased risk for bradycardic events
• Concomitant therapy with strong CYP3A
inhibitors/inducers
• Patients requiring dialysis
James S, et al. Am Heart J. 2009;157:599–605.
21. PLATO: Baseline Characteristics
Characteristic
Ticagrelor
(n=9,333)
Clopidogrel
(n=9,291)
Median age, years 62.0 62.0
Age ≥75 years, n (%) 1,396 (15.0) 1,482 (16.0)
Women, n (%) 2,655 (28.4) 2,633 (28.3)
CV risk factors, n (%)
Habitual smoker 3,360 (36.0) 3,318 (35.7)
Hypertension 6,139 (65.8) 6,044 (65.1)
Dyslipidemia 4,347 (46.6) 4,342 (46.7)
Diabetes mellitus 2,326 (24.9) 2,336 (25.1)
History, n (%)
MI 1,900 (20.4) 1,924 (20.7)
PCI 1,272 (13.6) 1,220 (13.1)
CABG 532 (5.7) 574 (6.2)
ECG at study entry, n (%)
ST-segment elevation, persistent 3,497 (37.5) 3,511 (37.8)
ST-depression 4,730 (50.7) 4,756 (51.2)
T-wave inversion 2,970 (31.8) 2,975 (32.0)
Troponin-I positive, n (%) 7,965 (85.3) 7,999 (86.0)
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
22. Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
Both groups included aspirin.
*NNT at one year.
PLATO: Primary Efficacy Endpoint
(Composite of CV Death, MI, or Stroke)
No. at risk
Clopidogrel
Ticagrelor
9,291
9,333
Months After Randomization
8,521
8,628
8,362
8,460
8,124 6,650
6,743
5,096
5,161
4,047
4,1478,219
0 2 4 6 8 10 12
12
11
10
9
8
7
6
5
4
3
2
1
0
13CumulativeIncidence(%)
11.7 Clopidogrel
9.8 Ticagrelor
ARR=0.6%
RRR=12%
P=0.045
HR: 0.88 (95% CI, 0.77−1.00)
0–30 Days
4.8
5.4
Clopidogrel
Ticagrelor
ARR=1.9%
RRR=16%
NNT=54*
P<0.001
HR: 0.84 (95% CI, 0.77–0.92)
0–12 Months
23. PLATO: Predefined Testing of Primary and
Major Secondary Efficacy Endpoints
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
All Patients*
Ticagrelor
(n=9,333)
Clopidogrel
(n=9,291)
HR for Ticagrelor
(95% CI)
P Value**
Primary endpoint, n (%/year)
Death from vascular cause + MI† + stroke 864 (9.8) 1,014 (11.7) 0.84 (0.77–0.92) <0.001
Secondary endpoints, n (%/yr)
Death from any cause + MI† + stroke 901 (10.2) 1,065 (12.3) 0.84 (0.77–0.92) <0.001
Death from vascular causes + MI† + stroke
+ severe recurrent ischemia + recurrent
ischemia + TIA + arterial thrombus
1,290 (14.6) 1,456 (16.7) 0.88 (0.81–0.95) <0.001
MI† 504 (5.8) 593 (6.9) 0.84 (0.75–0.95) 0.005
Death from vascular causes 353 (4.0) 442 (5.1) 0.79 (0.69–0.91) 0.001
Stroke 125 (1.5) 106 (1.3) 1.17 (0.91–1.52) 0.22
Death from any cause 399 (4.5) 506 (5.9) 0.78 (0.69–0.89) <0.001‡
Nominal
Significance
Both groups included aspirin.
The percentages presented are Kaplan-Meier estimates of the rate of the endpoint at 12 months.
* Patients could have had more than one type of endpoint. Death from CV causes and fatal bleeding, as only traumatic fatal bleeds were excluded
from the CV death category. ** By Cox regression analysis using treatment as factor; †Excluding silent MI; ‡Death from any cause was tested after
stroke, which was non-significant, so the results should be considered nominally significant.
24. Months After Randomisation
0 2 4 6 8 10 12
6
5
4
3
2
1
0
7
CumulativeIncidence(%)
Clopidogrel
Ticagrelor
5.8
6.9
0 2 4 6 8 10 12
6
4
3
2
1
0
Clopidogrel
Ticagrelor
4.0
5.1
7
5
Months After Randomisation
Myocardial Infarction Cardiovascular Death
CumulativeIncidence(%)
PLATO: Secondary Efficacy Endpoints
Rate of stroke for Ticagrelor was not different from clopidogrel (1.3% vs 1.1% ), P=0.225.
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057. Supplement.
ARR=1.1%
RRR=16%
Calculated NNT=91
P=0.005
HR: 0.84 (95% CI, 0.75–0.95)
ARR=1.1%
RRR=21%
NNT=91
P=0.001
HR: 0.79 (95% CI, 0.69–0.91)
Both groups included aspirin.
25. PLATO Primary Endpoint: Initial Invasive vs
Initial Non-Invasive Management
James S, et al. ESC. 2010; Poster #1353.
Cannon CP, et al. Lancet. 2010;375:283–293.
26. Stent Thrombosis ticagrelor vs clopidogrel
0,6%
ARR
33%
RRR
P = 0.009
Ticagrelor
n= 5640
Clopidogrel
n = 5649
Wallentin L, et al. N Engl J Med 2009;361:1045-57
* Definition by Academic Research Consortium criteria
27. PLATO Efficacy Results
Summary
Ticagrelor significantly reduced the composite of
CV death, MI or stroke vs clopidogrel at 1 year
(1.9% ARR, 16% RRR, P<0.001, NNT=54)
Ticagrelor significantly reduced CV mortality vs
clopidogrel
(1.1% ARR, 21% RRR, P=0.001)
Risk of CV death and MI were both significantly reduced
Risk of stroke was not significantly different
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
28. PLATO Efficacy Results
Summary
The absolute risk reduction with ticagrelor vs
clopidogrel starts early and continues to build
over the full 1 year treatment period
For every 91 ACS patients treated with
ticagrelor for 1 year, instead of clopidogrel, 1
CV death was prevented (NNT=91)
The effect of ticagrelor over clopidogrel
appears consistent across many subgroups
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
30. P=0.43
HR: 1.04 (95% CI, 0.95–1.13)
PLATO: Primary Safety Endpoint
PLATO-definedTotal
MajorBleeding(%)
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
Days From First Dose
10
5
0
15
0 60 120 180 240 300 360
Clopidogrel
Ticagrelor
11.2%
11.6%
P=NS
No. at risk
Clopidogrel
Ticagrelor
9,186
9,235
7,305
7,246
6,930
6,826
6,670 5,209
5,129
3,841
3,783
3,479
3,4336,545
Both groups included aspirin.
31. PLATO: Safety Endpoints - bleeding
*Both groups included aspirin; **Proportion of patients (%)
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
33. PLATO: Dyspnoea
• Ticagrelor-associated dyspnoea was mostly mild to moderate in severity
and did not reduce efficacy
• Most events were reported as single episode occurring early after starting
treatment
• Not associated with new or worsening heart or lung disease
BRILINTA. Indonesia Prescribing Information 2012.
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
Storey R, et al. Eur Heart J 2011;32:2945-2953
Dyspnoea in the PLATO trial Ticagrelor Clopidogrel P Value
Incidence of dyspnoea adverse events (%) 13.8 7.8 <0.001
Patients who discontinued treatment due to
dyspnoea (%)
0.9 0.1 <0.001
34. PLATO: Bradycardia-related Events
All Patients
Ticagrelor
(n=9,235)
Clopidogrel
(n=9,186) P Value
Bradycardia-related event, n (%)
Pacemaker insertion 82 (0.9) 79 (0.9) 0.87
Syncope 100 (1.1) 76 (0.8) 0.08
Bradycardia 409 (4.4) 372 (4.0) 0.21
Heart Block 67 (0.7) 66 (0.7) 1.00
• Ventricular pauses ≥3 seconds occurred in 5.8% of Ticagrelor-treated patients vs 3.6% of
clopidogrel-treated patients in the acute phase, and 2.1% and 1.7% after 1 month, respectively
• There were no differences in adverse clinical consequences (ie, pacemaker insertion, syncope,
bradycardia, and heart block)
1. Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.2. Scirica BM et al. J Am Coll Cardiol 2011;57:1908-1916
3. BRILINTA Indonesia Prescribing Information 2012.
35. PLATO: Laboratory Parameters
All Patients
Ticagrelor
(n=9,235)
Clopidogrel
(n=9,186) P Value
Mean % increase (± SD) in serum creatinine from
baseline
At 1 month 10 ± 22 8 ± 21 <0.001
At 12 months 11 ± 22 9 ± 22 <0.001
1 month after end of treatment 10 ± 22 10 ± 22 0.59
Mean % increase (± SD) in serum uric acid from
baseline
At 1 month 14 ± 46 7 ± 44 <0.001
At 12 months 15 ± 52 7 ± 31 <0.001
1 month after end of treatment 7 ± 43 8 ± 48 0.56
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
36. CI, confidence interval; CrCl, creatinine clearance; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction.
James S, et al. Circulation 2010;122:1056–1067.
Renal function and outcomes in PLATO: Primary
composite endpoint by CrCl
Ticagrelor
better
Clopidogrel
better
Risk of CV death, stroke or MI
HR (95% CI)
30
40
50
60
70
80
90
100
CrCl
(mL/min)
0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.20.4
Increasingrenalimpairment
37. PLATO Safety Results
Summary
No increase in overall major bleeding with
Ticagrelor vs clopidogrel
Non-CABG major bleeding and major + minor
bleeding were more frequent withTicagrelor
vs clopidogrel
No increase in overall fatal/life-threatening
bleeding withTicagrelor vs clopidogrel
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
38. PLATO Safety Results
Summary
There are more dyspnoea-related events
associated withTicagrelor vs clopidogrel,
however most events were mild to moderate
in intensity and often resolved without a need
for treatment
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
40. ESC Guidelines for the management of ACS in patients
presenting without persistent ST-segment elevation
Hamm CW et al. Eur Heart J 2011;32:2999 – 3054
41. LevelClass
Steg PG, et al. European Heart Journal. 2012;33:2569-2619
Oral antiplatelet in ESC
2012 STEMI Guideline
43. Summary
Ticagrelor is an active drug with reversible
binding to P2Y12 receptor
Ticagrelor provide fast onset and fast offset
Ticagrelor significantly reduces the combined
risk of CV death, MI, or stroke as compared to
clopidogrel in patients with ACS
44. Summary
Ticagrelor is effective in a broad spectrum of
ACS patients
There is no increase of overall major bleeding
withTicagrelor as compared to clopidogrel
Ticagrelor has been recommended in ACS
guidelines both in initial management ,
before PCI procedure and at discharge