title: Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.
abstract: BACKGROUND
  Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations.
  
  
  METHODS
  High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding.
  
  
  RESULTS
  Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF.
  
  
  CONCLUSIONS
  In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.
authors.affiliation: Medisch Centrum Alkmaar, Alkmaar, Netherlands. Electronic address: j.h.cornel@mca.nl.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Neely
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Danny
authors.initials: D
authors.lastname: Liaw
authors.affiliation: Johns Hopkins University, Baltimore, MD.
authors.forename: Julie
authors.initials: J
authors.lastname: Miller
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Puneet
authors.initials: P
authors.lastname: Mohan
authors.affiliation: Barwon Health Foundation, Geelong, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Amerena
authors.affiliation: Medical Institute, Ministry of Interior, Sofia, Bulgaria.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Raev
authors.affiliation: Peking University First Hospital, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Asociación Colombiana de Medicina Interna, Bogota, Colombia, Colombia.
authors.forename: Miguel
authors.initials: M
authors.lastname: Urina-Triana
authors.affiliation: Hospital Nacional Daniel A. Carrión, Bellavista, Peru.
authors.forename: Alex
authors.initials: A
authors.lastname: Gallegos Cazorla
authors.affiliation: University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.affiliation: Slovak Institute of Cardiovascular Disease, Bratislava, Slovakia.
authors.forename: Viliam
authors.initials: V
authors.lastname: Fridrich
authors.affiliation: Stanford University School of Medicine, Stanford, CA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000517:prevention & control*; D000284:Administration, Oral; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban