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Journal club : dual antiplatelets therapy Post AMI
Mahajna MuhammadSackler faculty of medicine
Tel-Aviv-Uni2015
This article was published on March 14,2015, at NEJM.org.
DOI: 10.1056/NEJMoa1500857
This article was published on March 14,2015, at NEJM.org.
DOI: 10.1056/NEJMoa1500857
Introduction and background
N=18,000
TRIAL ORGANIZATION
An Academic Research Organization ofBrigham and Women’s Hospital and Harvard Medical School
TIMI Study GroupEugene Braunwald (Chair) Marc P. Bonaca (Co-PI)S Morin & P Fish (Operations)
Executive CmteEugene Braunwald (Chair) Deepak L. BhattPh. Gabriel Steg
Sponsor: AstraZenecaPeter Held Per JohansonBarbro Boberg
Independent Data Monitoring CmteJeffrey L. Anderson (Chair) Freek W.A.VerheugtDavid L. DeMets
Marc S. Sabatine (PI)Stephen D. Wiviott (CEC Chair) SA Murphy & Kelly Im (Statistics)
Marc S. Sabatine Marc Cohen Robert Storey
Eva JensenAnn Maxe Ahlbom Olof Bengtsson
Terje R. Pedersen Harvey D. White
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-upin patients with a history of MI
Global enrollment
MethodsStudy design and oversightStudy populationRandomization and study treatment End pointsStatistical analysis
Trial design
Overall 33 months follow up
Bonaca MP et al. Am Heart J 2014;167:437-44
Ascertainment for primary endpoint was complete for 99% of potential patient-years of follow up
Randomized 21,162 patients
Ticagrelor 90 mg bid (N=7050)
Ticagrelor 60 mg bid (N=7045)
Placebo (N=7067)
Follow-up median 33 months (IQR 28-37)Minimum 16 months, maximum 47 months
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
~65~24%
~82
~54%
~40%
~6%
Key Inclusion & Exclusion Criteria
Bonaca MP et al. Am Heart J 2014;167:437-44
Endpoints
Efficacy : hierarchical testingPrimary : cardiovascular death , myocardial
infarction , stroke Secondary : all cause mortality + non-
coronary ischemic events , individual ischemic events
Safety : Primary : TIMI major bleeding Other : intracranial hemorrhage , fatal bleeding
[ death >7d]
TIMI major bleeding scale
http://spo.escardio.org/eslides/view.aspx?eevtid=33&id=5017
ResultsEfficacy vs
safety
Ticagrelor at any dose >placebo 60 mg as good as 90 mg ~ 15 %-19% relative risk reduction
10.1056/NEJMoa1500857
10.1056/NEJMoa1500857
Duration
Relative risk reduction
RR -REDUCTIO
N
Pooled Ticagrelor dose > placebo at coronary,cardiovascular,infarction,stroke prevention
90 mg > 60 mg at MI prevention 60 mg > 90 mg for stoke prevention
Bleeding
Discussion : limitation , comparison
All trials agree on the benefits of dual anti- platelet therapy after MI
DAPT trial : 1)Randomly assigned pts to continuing vs stopping a P2Y12
receptor antagonist after 12 moths2)Included pts who had not had clinically significant bleeding.3)Included pts who were able to keep taking a P2Y12 receptor
antagonist .4)All above minimize their bleeding complication In PEGASUS-TIMI 54 all Pts began treatment with Brilinta
after they complete the guidelines duration of therapy .They enrolled close to 2 years after MI
Considering side effects [ mainly dyspnea] : PLATO trial > PEGASUS-TIMI 541.Less stable Pts in PLATO study [ dyspnea is common during 1 year after MI ].2. PEGASUS-TIMI 54 had more stable Pts [ 3 years after MI] 3. PEGASUS-TIMI 54 reflects the real dyspnea ratio as a complication
PEGASUS-TIMI 54 : safety profile should not be generalized for all population
1)High risk of bleeding , previous stroke , anticoagulants usage were among the exclusion criteria
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 at all major groups and sub groups
• 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
Thanks
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