This document summarizes antiplatelet agents used in acute coronary syndrome. It discusses 3 oral P2Y12 inhibitors approved by the FDA - Clopidogrel, Prasugrel, and Ticagrelor. Clopidogrel was shown to reduce cardiovascular events in CURE trial but has slow onset and offset. Prasugrel provided greater platelet inhibition than Clopidogrel in TRITON trial but increased bleeding. Ticagrelor had faster, greater platelet inhibition than Clopidogrel and reduced mortality compared to Clopidogrel in PLATO trial. The document also discusses the IV P2Y12 inhibitor Cangrelor, which has very rapid onset and offset, and was shown to reduce periproced
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
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/
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 .
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.
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.
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/
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 .
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.
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.
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
http://www.theheart.org/web_slides/1364595.do
A study on Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) designed to determine whether vopaxar, when added to existing standard of care (eg, aspirin, clopidogrel) for preventing MI and stroke in patients with ACS, will provide additional benefit.
My journey to AHA 2016 Shanghai.
[Quote from AHA]
•AHA 大会是一个针对资深专业人士的武林小会,这个
武林小会有两个特点
•深- 在这里有各路门派的最顶尖高手,包括敏捷圈、测
试圈、技术圈、引导圈、专业教练圈、组织变革圈、视
觉圈里面的代表人物。
•跨-有机会一下子看到这么多门派的看家绝技,融合。
哪怕连小会的组委会都是一个跨界共创。
Generic Plavix Tablets (Clopivas) is an inhibitor of platelet activation and is used to prevent blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease.
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.
Follow us on: Pinterest
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
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
5. Clopidogrel
• Oral thienopyridine
• Irreversible ADP P2Y12 receptor blocker
• Is a prodrug that is converted to active
metabolites through oxidation by the hepatic
cytochrome P-450 system
6. Clopidogrel
• CURE 2001
– Patients with non STE ACS who had presented within 24
hours after the onset of symptoms.
– Clopidogrel vs Placebo
– ~ 6000 in each arm
– Primary outcome a composite endpoint of death, non
fatal MI, Stroke
– 21% PCI rate (conservative therapy)
CURE investigators NEJM 2001
7.
8.
9.
10. • ARR 2.1% in the composite endpoint
• Reduction in non fatal MI, with a favorable trend
towards benefit with Clopidogrel in death from
cardiovascular causes and stroke
• More major bleeding in the Clopidogrel group ARI 1%
• Predominantly in patients who underwent CABG less
than 5 days after stopping Clopidogrel
11. AHA/ACC 2007
• All patients with ACS should receive
Clopidogrel, loading dose followed by
maintenance, regardless of choice selective
invasive or invasive (Class I)
• For a duration of 1 month minimum, ideally
one year (Class I)
• Stop Clopidogrel 5-7 days before CABG
15. CABG in ACS with clopidogrel on board
• 30% of patients undergoing CABG have
received clopidogrel
• 90% of them get CABG in less than 5 days
• Operating in less than 5 days with clopidogrel
on board
– More blood transfusion rates, and more blood given
– 1% additional risk of MI while waiting for CABG
Mehta et al JACC 2006 ; CRUSADE Registry
16. Emergency Reversal of Clopidogrel
• No antidote
• Platelet transfusion
– Invitro studies of healthy volunteers
• Recombinant Factor VII
– Invitro studies of healthy volunteers
– Renal transplant patients improved bleeding time
• DDAVP ( n=1)
– Severe epistaxis
Beshay et al Journal of Neurosurgery 2010: Review
17. Clopidogrel a good drug with
drawbacks
•
•
Proven benefit
Drawbacks
1. Slow onset ;can be minimized by administering
600mg loading dose
2. Slow offset; (5 days wait before CABG can be
safe to perform)
3. Variability in response up to 21% non
responders, who will have higher risk of MI and
stent thrombosis
4. No antidote
18. May 17th 2012
Clopidogrel goes off patent
Medication
Price per day
Clopidogrel
Generic
Clopidogrel
Brand
Prasugrel
$0.37
Ticagrelor
$7.11
$4.00
$5.78
19. Is Generic Clopidogrel as good as Plavix?
Caldiera et al. Journal of Cardiovascular Pharmacology 2013
20. Prasugrel
• Oral thienopyridine
• Irreversible ADP P2Y12 receptor blocker
• 2 step activation process without significant
genetic polymorphism
• Faster onset of action
• More potent Higher rates of platelet
aggregation
21. LD and repeated pre-dose at days 14 and 29.
Results: There was no significant difference in clinical characteristics o
level at baseline. 106 patients completed the study (54 on prasugrel and
clopidogrel). Treatment was well tolerated in both groups. As illustrated
figure the mean MPA levels were significantly (p< 0.0001) lower with prasu
all time-points after start of treatment.
Faster, more potent
Varenhorst et al. ESC 2007 Congress Abstract
23. TRITON TIMI 38
• 13,608 patients with moderate-to-high-risk ACS planned for
PCI (99% underwent PCI)
• Prasugrel 60mg loading dose followed by 10mg maintenance
• Clopidogrel 300 mg loading dose followed by 75mg
maintenance dose for 6 to 15 months.
• Difference from CURE population
–
–
–
–
–
25% STEMIs compared to none
50% GPIIbIIIa compared to none
Higher use of statins 92% vs. 25% at time of randomization
Higher use of BBs 88% vs. 58%
Higher use of ACEI 76% vs. 37%
Wiviott et al. NEJM 2007
24.
25.
26.
27. •
•
•
•
•
•
•
•
ARR in composite endpoint 2.2% with Prasugrel
ARR 2.3% in MI with Prasugrel
ARR in Death from cardiovascular cause 0.3% NS
Major bleeding ARI 0.6%
Fatal bleeding ARI 0.3%
So Prasugrel use contraindicated in PH of TIA/Stroke
Caution in > 75, and low BMI
Discontinue 7 days before CABG
28.
29. Timing of Prasugrel administration
• On the table administration after diagnostic
angiography and decision of PCI taken in
TRITON TIMI 38
• FDA Package Insert/ Class IIb Recommendation
– “it is reasonable to consider selective use of
prasugrel before catheterization in subgroups of
patients for whom a decision to proceed to
angiography and PCI has already been established
for any reason. “
30. ACCOAST
•
•
•
•
•
N ~4000
NSTE ACS with +ve troponin
PCI planned in 2-48 hours
30mg upfront then 30mg in Cath Lab vs
60mg in Cath Lab
Montalescot et al. NEJM 2013
33. TRILOGY ACS
•
•
•
•
Role of Prasugrel beyond PCI patients
NSTE ACS, USA did not undergo PCI (< 75 yrs)
Clopidogrel vs Prasugrel
No difference in composite primary endpoint
(Death, non fatal MI, Revasc)
• Trend towards less ischemic events and more
minor bleeding with prasugrel
Roe et al. NEJM 2012
34. Prasugrel
• More reliable than clopidogrel
• Higher efficacy
• More bleeding
– Avoid in bleeders
• Initiate in Cath Lab
• If CABG needed 7 day wait
35. Ticagrelor
• Ticagrelor, a reversible and direct-acting oral ADP
receptor blocker (P2Y12)
• faster, greater, and more consistent
P2Y12 inhibition than Clopidogrel (possibly more
than Prasugrel)
• 90mg twice daily is the dose used in PLATO, higher
doses were associated with more side effects
(dyspnea, ventricular pauses)
38. PLATO
• Multicenter, randomized, double blind
, double dummy clinical trial
• 18,624 patients from 862 centers in 43
countries from October 2006 through July
2008
• The follow-up period ended in February 2009
Wallentin et al. NEJM 2009
39. Study Design
• Ticagrelor group
– given in a loading dose of 180 mg followed by a
dose of 90 mg twice daily.
• Clopidogrel group
– 300-mg loading dose followed by a dose of 75 mg
– OR maintenance dose of 75 mg if already on
Clopidogrel
46. What does PLATO brings to the table?
1. More platelet inhibition not necessarily
more overall harm
– CURE, TRITON TIMI 18 showed that more
platelet inhibition equaled less MI, less urgent
revascularization,
– more bleeding, and in case of Prasugrel more
life threatening, and fatal bleeding
– Ticagrelor patients bled more (albeit not
significantly) than Clopidogrel, but less during
CABG
47. 2. Ticagrelor saves lives
No significant mortality benefit in CURE with
Clopidogrel in non ST ACS, or TRITON TIMI 38 with
Prasugrel in all ACS, or the GPIIb/IIIa trials.
PLATO shows mortality benefit like aspirin in all ACS
?play of chance as the trial not powered to detect
difference in mortality,
but consistent benefit across MACE with less
bleeding might be a possibility
48. 3. New side effects with Ticagrelor
Dyspnea
•
•
Mild, early, transient with no changes on
PFTs, Imaging
Similar to adenosine reaction in non invasive stress
testing
Bradycardia
Pauses
49. ³75 Years
Sex
Male
Female
Weight Group
<60 kg
³60 kg
<80 kg
³80 kg
Medical History of DM
No
Yes
Region
Asia/Australia
Central/South America
Europe/Middle East/Africa
North America
2878
16.8
18.3
0.94 (0.78, 1.12)
0.82
13336
5288
9.2
11.2
1312
17256
9055
9513
13.1
9.5
11.4
8.3
11.1
13.2
0.85 (0.76, 0.95)
0.83 (0.71, 0.97)
17.3
11.2
12.8
10.5
0.75 (0.60, 0.99)
0.86 (0.78, 0.94)
0.90 (0.79, 1.01)
0.79 (0.69, 0.90)
Subgroup
analysis
0.36
0.17
0.49
• Benefits of Ticagrelor were
8.4
10.2
0.83 (0.74, 0.92)
14.1
16.2
0.88 (0.76, 1.03)
seen across 62/66 subgroups
0.05
1714• 11.4
14.8
0.80 (0.61, 1.04)
Trend towards harm in those
1237
15.2
17.9
0.86 (0.65, 1.13)
enrolled in North America
13859
8.8
11.0
0.80 (0.72, 0.90)
13962
4662
1814
11.9
9.6
1.25 (0.93, 1.67)
Antiplatelet Therapy Prior to Index Event
0.43
Clopidogrel ± ASA
1397
15.8
17.8
0.95 (0.73, 1.24)
ASA
5024
11.8
14.0
0.84 (0.71, 0.98)
None
12147
8.2
10.0
0.82 (0.73, 0.93)
ASA on Day of Rand.
No
Yes
0.86
927
11.6
13.8
0.87 (0.60, 1.27)
17697
9.7
11.6
0.84 (0.77, 0.93)
GPIIb/IIIa (IE to End of Index Hosp.)
0.41
No
13562
9.7
11.9
0.82 (0.74, 0.92)
Yes
5062
10.0
11.1
0.90 (0.76, 1.07)
Race
Caucasian
0.66
17077
9.5
11.2
0.85 (0.77, 0.94)
50.
51. • 2 independent statistical analyses reached:
Aspirin dose >300 in US (53.6%) compared to
rest of the world (1.7%) may explain the
geographic variation in outcomes
52.
53.
54. Devil in the detail OR
paranoid conspiracy theory
58. CHAMPION trials
• Champion PCI – (Harrington, NEJM 2009)
– Cangrelor vs clopidogrel 600mg (before PCI)
– Negative trial
• Champion Platform – (Bhatt, NEJM 2009)
– Cangrelor vs clopidogrel 600mg (at end of PCI)
– Negative Trial (less ST, less death trend)
• Champion Phoenix (Bhatt, NEJM 2013)
– Cangrelor vs clopidogrel 600mg or 300mg (start or end of
PCI)
– Changed periprocedural MI to include (ECG changes, new
angio changes)
– Positive trial
– ARR 1.2 % driven by reduction in MI, also less ST
Platelet AdhesionPlatelet ActivationPlatelet AggregationPAR-1 protease activated receptorTRACER, stopped early due to excess bleedingAPPRAISE-2, stopped early due to bleeding complications including stroke, used the A fib anticoagulation dose 5mg BIDATLAS ACS TIMI 51, less ischemic events but more bleeding, used a lower dose 2.5mg BID, 5mg BID ; approved europeChamp trial, no benefit, more bleedingAcquity, bivalirudinvs heparin Iib/IIIavsbivalirudin / IIbIIIa
Composite endpoint of death from cardiovascular cause, non fatal MI, Stroke
Major bleeding according to TIMI definition
NNT = 50
Patients undergoing PCI , 1/3 stable angina, ½ unstable angina, 15% NSTEMIs300mg dose of plavix
Carriers of the CYP2C19 loss of function
Patients undergoing PCI who were on one year dual antiplatelet, VerifyNow Assay to assess platelet reactivity1 arm reload with 600mg and maintain on 150mg1 arm main
Minority need C
2 adult doses of plateletsRepeated platetet transfusion for 4-5 days
2 RCTs, 1 observerational cohort
Similar to mechanism of action to Clopidogrel
Randomized to prasugrel and clopidogrel
Composite endpoint of death due to cardiovascular cause, non fatal MI, ischemic stroke
Lives saved 0.3%
Lives lost 0.3%
Prasugrel Lesson: More platelet inhibition not necessarily better outcomes
4 hours from loading dose to Cath
Full antiplatelet activity at sheath insertion, if you go to CABG17% major bleeding in pretreated compared to 10%
Criticized for not giving a loading dose of 600mg
Major bleeding 11.6, 11.2% vs. 5, 3.8% in TRITON vs. 3.7, 2.7% in CURE