title: Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial.
abstract: BACKGROUND
  Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen.
  
  
  METHODS
  TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide. Patients with non-ST-elevation acute coronary syndrome who were selected for management without [corrected] revascularisation were randomly assigned to clopidogrel or prasugrel.The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months. In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not.
  
  
  RESULTS
  7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis. 3085 (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan-Meier analysis (281/3085 [12·8%] vs 480/4158 [16·5%], adjusted hazard ratio [HR] 0·63, 95% CI 0·53-0·75; p<0·0001). The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10·7%] vs 159/1561 [14·9%], HR 0·77, 95% CI 0·61-0·98; p=0·032) but did not differ between groups in patients who did not have angiography (242/2096 [16·3%] vs 238/2062 [16·7%], HR 1·01, 0·84-1·20; p=0·94; pinteraction=0·08). Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort.
  
  
  CONCLUSIONS
  Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention.
  
  
  BACKGROUND
  Daiichi Sankyo, Eli Lilly.
authors: Cardiovascular Division, Brigham and Women's Hospital, TIMI Study Group, Harvard Medical School, Boston, MA, USA. swiviott@partners.org
authors: Stephen D
authors: SD
authors: Wiviott
authors: Harvey D
authors: HD
authors: White
authors: E Magnus
authors: EM
authors: Ohman
authors: Keith A A
authors: KA
authors: Fox
authors: Paul W
authors: PW
authors: Armstrong
authors: Dorairaj
authors: D
authors: Prabhakaran
authors: Gail
authors: G
authors: Hafley
authors: Yuliya
authors: Y
authors: Lokhnygina
authors: William E
authors: WE
authors: Boden
authors: Christian
authors: C
authors: Hamm
authors: Peter
authors: P
authors: Clemmensen
authors: Jose C
authors: JC
authors: Nicolau
authors: Alberto
authors: A
authors: Menozzi
authors: Witold
authors: W
authors: Ruzyllo
authors: Petr
authors: P
authors: Widimsky
authors: Ali
authors: A
authors: Oto
authors: Jose
authors: J
authors: Leiva-Pons
authors: Gregory
authors: G
authors: Pavlides
authors: Kenneth J
authors: KJ
authors: Winters
authors: Matthew T
authors: MT
authors: Roe
authors: Deepak L
authors: DL
authors: Bhatt
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000401:mortality; D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy* / Q000401:mortality; D000077144:Clopidogrel; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D010879:Piperazines / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control; D013876:Thiophenes / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine