title: The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials.
abstract: OBJECTIVE
  The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.
  
  
  RESULTS
  We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98).
  
  
  CONCLUSIONS
  In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.
authors: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK david.preiss@glasgow.ac.uk.
authors: David
authors: D
authors: Preiss
authors: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
authors: Ross T
authors: RT
authors: Campbell
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors: Heather M
authors: HM
authors: Murray
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors: Ian
authors: I
authors: Ford
authors: Glasgow Clinical Research Facility, Western Infirmary, Glasgow, UK.
authors: Chris J
authors: CJ
authors: Packard
authors: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
authors: Naveed
authors: N
authors: Sattar
authors: George Institute for Global Health, University of Oxford, Oxford, UK.
authors: Kazem
authors: K
authors: Rahimi
authors: Medical Research Institute, University of Dundee, Dundee, UK.
authors: Helen M
authors: HM
authors: Colhoun
authors: Department of Medicine, University of California, San Francisco, CA, USA.
authors: David D
authors: DD
authors: Waters
authors: SUNY Health Science Center at Brooklyn, New York, NY, USA.
authors: John C
authors: JC
authors: LaRosa
authors: Department of Neurology and Stroke Center, Bichat University Hospital, Paris, France.
authors: Pierre
authors: P
authors: Amarenco
authors: University of Oslo and Centre for Preventative Medicine, Oslo University Hospital, Ullevål, Oslo, Norway.
authors: Terje R
authors: TR
authors: Pedersen
authors: University of Helsinki and Heart and Lung Center, Helsinki University Central Hospital and Folkhälsan Research Center, Helsinki, Finland.
authors: Matti J
authors: MJ
authors: Tikkanen
authors: Jacksonville Center for Clinical Research, Jacksonville, FL, USA.
authors: Michael J
authors: MJ
authors: Koren
authors: International Center for Circulatory Health, National Heart & Lung Institute, Imperial College London, London, UK.
authors: Neil R
authors: NR
authors: Poulter
authors: International Center for Circulatory Health, National Heart & Lung Institute, Imperial College London, London, UK.
authors: Peter S
authors: PS
authors: Sever
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Paul M
authors: PM
authors: Ridker
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Jean G
authors: JG
authors: MacFadyen
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Scott D
authors: SD
authors: Solomon
authors: The University of Texas School of Public Health, Houston, TX, USA.
authors: Barry R
authors: BR
authors: Davis
authors: The University of Texas School of Public Health, Houston, TX, USA.
authors: Lara M
authors: LM
authors: Simpson
authors: Mitsukoshi Health and Welfare Foundation, Shinjuku-ku, Tokyo, Japan.
authors: Haruo
authors: H
authors: Nakamura
authors: Department of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors: Kyoichi
authors: K
authors: Mizuno
authors: Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Rosa M
authors: RM
authors: Marfisi
authors: Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Roberto
authors: R
authors: Marchioli
authors: Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors: Gianni
authors: G
authors: Tognoni
authors: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
authors: Vasilios G
authors: VG
authors: Athyros
authors: International Center for Circulatory Health, National Heart & Lung Institute, Imperial College London, London, UK.
authors: Kausik K
authors: KK
authors: Ray
authors: Weill Cornell Medical College, New York, NY, USA.
authors: Antonio M
authors: AM
authors: Gotto
authors: College of Osteopathic Medicine, Touro University, Vallejo, CA, USA.
authors: Michael B
authors: MB
authors: Clearfield
authors: Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA The South Texas Veterans Health Care System, San Antonio, TX, USA.
authors: John R
authors: JR
authors: Downs
authors: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
authors: John J
authors: JJ
authors: McMurray
mesh_terms: D005260:Female; D006333:Heart Failure / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Heart failure; Meta-analysis; Prevention; Randomized trial; Statin