journal club- dual-antiplatelets therapy Post AMI
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This study evaluated the efficacy and safety of adding ticagrelor to low-dose aspirin in stable patients with a history of myocardial infarction. Over 18,000 patients were randomly assigned to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo twice daily in addition to standard medical therapy including aspirin. The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. The results showed that ticagrelor at either dose reduced the risk of the primary outcome compared to placebo by 16-19% with no significant difference between the two ticagrelor doses. Ticagrelor increased the risk of TIMI major bleeding but not fatal bleeding or intracere
![Endpoints
Efficacy : hierarchical testing
Primary : cardiovascular death , myocardial infarction ,
stroke
Secondary : all cause mortality + non-coronary ischemic
events , individual ischemic eventsSafety :
Primary : TIMI major bleeding
Other : intracranial hemorrhage , fatal bleeding [ death >7d]](https://image.slidesharecdn.com/jc2015-170404175924/85/journal-club-dual-antiplatelets-therapy-Post-AMI-15-320.jpg)
![ Considering side effects [ mainly dyspnea] : PLATO trial > PEGASUS-TIM
1. Less stable Pts in PLATO study [ dyspnea is common during 1 year after
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](https://image.slidesharecdn.com/jc2015-170404175924/85/journal-club-dual-antiplatelets-therapy-Post-AMI-29-320.jpg)
journal club- dual-antiplatelets therapy Post AMI
- 1. Journal club : dual antiplatelets therapy Post AMI Mahajna Muhammad Sackler faculty of medicine Tel-Aviv-Uni 2015 This article was published on March 14, 2015, at NEJM.org. DOI: 10.1056/NEJMoa1500857
- 2. This article was published on March 14, 2015, at NEJM.org. DOI: 10.1056/NEJMoa1500857
- 5. N=18,000
- 6. An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School TIMI Study Group Eugene Braunwald (Chair) Marc P. Bonaca (Co-PI) S Morin & P Fish (Operations) Executive Cmte Eugene Braunwald (Chair) Deepak L. Bhatt Ph. Gabriel Steg Sponsor: AstraZeneca Peter Held Per Johanson Barbro Boberg Independent Data Monitoring Cmte Jeffrey L. Anderson (Chair) Freek W.A.Verheugt David L. DeMets Marc S. Sabatine (PI) Stephen D. Wiviott (CEC Chair) SA Murphy & Kelly Im (Statistics) Marc S. Sabatine Marc Cohen Robert Storey Eva Jensen Ann Maxe Ahlbom Olof Bengtsson Terje R. Pedersen Harvey D. White
- 7. 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
- 9. Methods Study design and oversight Study population Randomization and study treatment End points Statistical analysis
- 10. Trial design Overall 33 months follow up Bonaca MP et al. Am Heart J 2014;167:437-44
- 11. 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
- 12. ~65 ~24% ~82
- 13. ~54% ~40% ~6%
- 14. Key Inclusion & Exclusion Criteria Bonaca MP et al. Am Heart J 2014;167:437-44
- 15. Endpoints Efficacy : hierarchical testing Primary : cardiovascular death , myocardial infarction , stroke Secondary : all cause mortality + non-coronary ischemic events , individual ischemic eventsSafety : Primary : TIMI major bleeding Other : intracranial hemorrhage , fatal bleeding [ death >7d]
- 16. TIMI major bleeding scale http://spo.escardio.org/eslides/view.aspx?eevtid= 33=di&5017
- 18. Ticagrelor at any dose >placebo 60 mg as good as 90 mg ~ 15 %-19% relative risk reduction
- 22. Pooled Ticagrelor dose > placebo at coronary,cardiovascular,infarction,stroke prevention 90 mg > 60 mg at MI prevention 60 mg > 90 mg for stoke prevention
- 24. Bleeding
- 26. Discussion : limitation , comparison
- 28. 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 moths 2) 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
- 29. Considering side effects [ mainly dyspnea] : PLATO trial > PEGASUS-TIM 1. Less stable Pts in PLATO study [ dyspnea is common during 1 year after 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
- 30. summary
- 31. • 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
- 32. Thanks