title: Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38).
abstract: OBJECTIVE
  The goal of this study was to determine whether there is a relationship between aspirin dose and the potent antiplatelet agent prasugrel in the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) study.
  
  
  BACKGROUND
  Optimal aspirin dosing after acute coronary syndromes remains uncertain. Previous studies have raised questions regarding an interaction between high-dose aspirin and the potent antiplatelet agent ticagrelor.
  
  
  METHODS
  In TRITON-TIMI 38, we classified 12,674 patients into low-dose (<150 mg) or high-dose (≥150 mg) aspirin groups based on discharge dose. We identified independent correlates of dose selection and studied the impact of aspirin dose on the clinical effects of prasugrel.
  
  
  RESULTS
  There was significant geographical variation in aspirin dosing, with North American patients receiving high-dose aspirin more frequently than other countries (66% vs. 28%; p < 0.001). Clinical factors correlating with high-dose aspirin included previous percutaneous coronary intervention and use of aspirin before randomization. Characteristics associated with the use of low-dose aspirin included age ≥75 years, white race, and use of bivalirudin or a glycoprotein IIb/IIIa inhibitor during coronary intervention. Regardless of low- or high-dose aspirin use, prasugrel had lower rates of the primary efficacy endpoint (cardiovascular death, myocardial infarction, or stroke [CVD/MI/stroke]) (hazard ratio [HR]CVD/MI/stroke = 0.78 [95% confidence interval (CI) 0.64 to 0.95] and HRCVD/MI/stroke = 0.87 [95% CI 0.69 to 1.10], respectively; p value for interaction = 0.48) and higher rates of the primary safety endpoint (HR TIMI major bleeding = 1.40 [95% CI 0.81 to 2.42] and TIMImajor bleeding = 1.30 [95% CI 0.63 to 2.68], respectively; p value for interaction = 0.84) compared with clopidogrel.
  
  
  CONCLUSIONS
  In TRITON-TIMI 38, the safety and efficacy outcomes of prasugrel compared with those of clopidogrel were directionally consistent regardless of aspirin dose, although only the primary efficacy endpoint achieved statistical significance. There was no clinically meaningful interaction of aspirin with prasugrel, suggesting that previous observations with potent antiplatelet agents indicating differential results are not universal. (A Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).
authors.affiliation: University of California San Francisco, Division of Cardiology, San Francisco, California; TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.affiliation: TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Udell
authors.affiliation: TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: TIMI Study Group Division of Cardiology, Department of Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: swiviott@partners.org.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D010351:Patient Discharge; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin
keywords: ACS; ADP; CABG; CI; COX; CVD; HR; NSTEMI; OR; PCI; TIMI; Thrombolysis in Myocardial Infarction; acute coronary syndrome(s); adenosine diphosphate; aspirin dose; cardiovascular death; confidence interval; coronary artery bypass grafting; cyclooxygenase; hazard ratio; non–ST-segment elevation myocardial infarction; odds ratio; outcomes; percutaneous coronary intervention; prasugrel