The New england journal of medicine March 14, 2015 Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction The New england journal of medicine March 14, 2015 Marc P. Bonaca, M.D., M.P.H., Deepak L. Bhatt, M.D., M.P.H., Marc Cohen, M.D., Philippe Gabriel Steg, M.D., Robert F. Storey, M.D., Eva C. Jensen, M.D., Ph.D., Giulia Magnani, M.D., Sameer Bansilal, M.D., M. Polly Fish, B.A., Kyungah Im, Ph.D., Olof Bengtsson, Ph.Lic 내과 R3 문정락/IC prof. 김현수 수요저널 발표를 시작하겠습니다. 본저널은 2015년 3월 14일 NEJM 에 실린 논문으로 MI Hx 있는 환자 에게서 ticagrelor 의 long term 한 사용의 효과에 대해 연구한 논문입니다. 저는 3년차 문정락이고 modulator 교수님은 김현수 교수님 이십니다.

Back Ground Aspirin reduces the risk of ischemic events both among patients who present with an ACS and in secondary prevention for patients with a history of MI. The addition of a P2Y12 receptor antagonist to aspirin has been shown to reduce further the risk of ischemic events in this population in the first year after an ACS Back round 보시겠습니다. Aspirin 은 ACS 환자에서, MI 환자에서 2차적인 ischemic event 의 위험성을 감소 시켜주는 효과가 있다는 것은 이미 알려진 사실입니다. Aspirin 에 p2y12 receptor antagonist 를 더하여 사용하는 것은 ACS 후 1년까지 ischemic event 의 risk 를 감소시켜준다는 것도 이미 알려져 있습니다.

Ticagrelor is a potent, reversibly binding, direct acting P2Y12 receptor antagonist. When added to aspirin for 1 year after an ACS, Ticagrelor at a dose of 90 mg twice daily reduced the rate of major adverse cardiovascular events including cardiovascular death, as compared with clopidogrel at a dose of 75 mg once daily Ticagrelor 는 P2Y receptor 에 직접적으로 작용하는 강력한 antagonist 입니다. ACS 1년까지 Aspirin 에 add해서 clopidogrel 75mg 을 하루 한번 사용하는 것보다 90mg bid 용량의 ticagrelor 를 사용하는 것은 cardiovascular death 를 포함한 event 들을 감소시켜주는 데에 도움이 될 수 있습니다.

PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction ) to test the hypothesis that long-term therapy with ticagrelor added to low-dose aspirin reduces the risk of major adverse cardiovascular events among stable patients with a history of myocardial infarction

Methods Study design and oversight Randomized, double-blind, placebo-controlled clinical trial Randomization at 1161 sites in 31 countries Study population spontaneous MI 1 to 3 years before enrollment at least 50 years of age one of the following additional high-risk features Age of 65 years or older DM requiring medication A second prior spontaneous myocardial infarction Multivessel coronary artery disease Chronic renal dysfunction (CrCl ≤ 60 ml /min)

Ineligible If there was planned use of a P2Y12 receptor antagonist, dipyridamole, cilostazol, or anticoagulant therapy during the study period Bleeding disorder or a history of an ischemic stroke or intracranial bleeding CNS tumor, or an intracranial vascular abnormality GI bleeding within the previous 6 months Major surgery within the previous 30 days

Randomization & Study treatment Eligible patients were randomly assigned, in a 1:1:1 ratio Ticagrelor orally at a dose of 90 mg twice daily Ticagrelor orally at a dose of 60 mg twice daily Placebo All the patients were to take aspirin at a dose of 75 to 150 mg daily.

The primary end point : TIMI major bleeding. efficacy The primary end point : cardiovascular death, myocardial infarction, or stroke. Secondary end points : cardiovascular death and death from any cause safety The primary end point : TIMI major bleeding. Other end points : ICH and fatal bleeding.

Result N=21,162 결론 보시겠습니다. 총 21162명을 대상으로 연구가 진행되었고 1:1:1 ratio로 randomization 했으며 두군간의 baseline characteristics 는 의미 있는 차이가 없었습니다.

Conclusion In conclusion, the addition of Ticagrelor to low-dose aspirin Reduced the risk of cardiovascular death, MI, or stroke Increased in the risk of TIMI major bleeding among patients who had had a MI 1 to 3 years earlier