title: Trends in clinical trials of non-ST-segment elevation acute coronary syndromes over 15 years.
abstract: BACKGROUND
  Data are limited on whether clinical trials have randomized higher-risk patients over time and how trends in risk profiles and evidence-based pharmacotherapies have influenced trial outcomes. We quantified changes in baseline risk, treatment, and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) randomized in 9 phase 3 clinical trials of antithrombotic therapy over 15 years.
  
  
  METHODS
  We studied 58,771 patients in GUSTO IIb, PURSUIT, PARAGON-A, PARAGON-B, PRISM, PRISM-PLUS, GUSTO IV-ACS, SYNERGY, and EARLY ACS. Patient-level data were mapped to 3 pre-specified 5-year randomization periods. Temporal trends in GRACE score-predicted mortality were compared with trends in observed mortality.
  
  
  RESULTS
  Over time, in-hospital and discharge use of thienopyridines (p=0.001), statins (p<0.0001), and angiotensin-converting enzyme inhibitors (p<0.0001) increased, and hospital length-of-stay decreased (p=0.024). Blood transfusion use increased (8.3% [1994-98], 10.7% [1999-2003], 13% [2004-08], p=0.0002) despite stable rates of severe bleeding (0.9% [1994-98], 1.4% [1999-2003] and 1.1% [2004-08], p=0.127) and coronary artery bypass grafting (12.4% [1994-98], 13.7% [1999-2003] 13.1% [2004-08], p=0.880). Although predicted 6-month mortality increased (6.9% [1994-98], 9.0% [1999-2003], 7.9% [2004-08], p=0.017), observed 6-month mortality decreased (6.7% [1994-98], 5.8% [1999-2003], 5.1% [2004-08], p=0.025). Thirty-day myocardial infarction rates remained stable (9.2% [1994-98], 9.3% [1999-2003], 10% [2004-08], p=0.539).
  
  
  CONCLUSIONS
  Despite enrolling higher-risk patients into these NSTE ACS trials, with better treatment, observed mortality declined over the past 15 years. The appropriateness of increased blood transfusion despite unchanged bleeding rates deserves further study.
authors.affiliation: National University Heart Center, Singapore, Singapore. mark_chan@nuhs.edu.sg
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Chan
authors.forename: Jie-Lena
authors.initials: JL
authors.lastname: Sun
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: Pierre
authors.initials: P
authors.lastname: Théroux
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Simoons
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D017326:Clinical Trials, Phase III as Topic / Q000639:trends*; D006801:Humans; D007902:Length of Stay / Q000639:trends*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000639:trends*