title: Elderly patients with acute coronary syndromes managed without revascularization: insights into the safety of long-term dual antiplatelet therapy with reduced-dose prasugrel versus standard-dose clopidogrel.
abstract: BACKGROUND
  Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d).
  
  
  RESULTS
  A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75 years of age, n=7243; ≥75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those ≥75 or <75 years of age and <60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for ≤30 months. A total of 515 participants ≥75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were ≥2-fold higher in older participants. Among those ≥75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants ≥75 years of age in the platelet-function substudy (P=0.06). No differences in weight were seen in all participants ≥75 years of age with versus without TIMI major/minor bleeding in both treatment groups.
  
  
  CONCLUSIONS
  Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov/ct2/home. Unique identifier: NCT0069999.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. matthew.roe@duke.edu
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.forename: Judith S
authors.initials: JS
authors.lastname: Hochman
authors.forename: Shmuel
authors.initials: S
authors.lastname: Gottlieb
authors.forename: Felipe
authors.initials: F
authors.lastname: Martinez
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Dalby
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.forename: Philip E
authors.initials: PE
authors.lastname: Aylward
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bassand
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D019468:Disease Management; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; 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: aging; drug therapy; fibrinolytic agents; myocardial infarction; receptors, purinergic P2Y12