title: Risk of heart failure and edema associated with the use of pregabalin: a systematic review.
abstract: BACKGROUND
  Pregabalin is used in the treatment of postherpetic neuralgia, diabetic neuropathic pain, partial seizures, anxiety disorders and fibromyalgia. Recognized adverse effects associated with its use include cognitive impairment, somnolence and dizziness. Heart failure associated with pregabalin has been described, however the strength of this association has not been well characterized. To examine this further, we will conduct a systematic review of the risk of heart failure and edema associated with use of pregabalin.
  
  
  METHODS
  We will include all studies (experimental, quasi-experimental, observational, case series/reports, drug regulatory reports) that examine the use of pregabalin compared to placebo, gabapentin or conventional care. Our primary outcome is heart failure and the secondary outcomes include edema and weight gain. We will search electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), and grey literature sources (trial registries, conference abstracts) to identify relevant studies. To ensure literature saturation, we will contact drug manufacturers, conduct forward citation searching, and scan the reference lists of key articles and included studies. We will not restrict inclusion by language or publication status.Two reviewers will screen citations (titles and abstracts) and full-text articles, conduct data abstraction, and appraise risk of bias. Random-effects meta-analysis will be conducted if the studies are deemed heterogeneous in terms of clinical, statistical and methodological factors but still suitable for meta-analysis.
  
  
  CONCLUSIONS
  The results of this review will assist physicians to better appreciate pregabalin's risk for edema or congestive heart failure and will be pertinent to the thousands of patients worldwide who are administered this medication.Our protocol was registered in the PROSPERO database (CRD42012002948).
authors: Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. jm.ho@mail.utoronto.ca
authors: Joanne M
authors: JM
authors: Ho
authors: Andrea C
authors: AC
authors: Tricco
authors: Laure
authors: L
authors: Perrier
authors: Maggie
authors: M
authors: Chen
authors: David N
authors: DN
authors: Juurlink
authors: Sharon E
authors: SE
authors: Straus
mesh_terms: D004487:Edema / Q000139:chemically induced*; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D017063:Outcome Assessment, Health Care; D000069583:Pregabalin; D012107:Research Design; D012196:Review Literature as Topic; D012306:Risk; D015430:Weight Gain / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
references: Control Clin Trials. 1986 Sep;7(3):177-88
references: 3802833
references: J Cardiovasc Med (Hagerstown). 2008 Sep;9(9):922-5
references: 18695430
references: Int J Epidemiol. 2007 Jun;36(3):666-76
references: 17470488
references: J Card Fail. 2007 Apr;13(3):227-9
references: 17448421
references: J Clin Epidemiol. 2010 May;63(5):502-12
references: 18823754
references: BMJ. 1997 Sep 13;315(7109):629-34
references: 9310563
references: PLoS One. 2008 Aug 28;3(8):e3081
references: 18769481
references: BMJ. 2011 Oct 18;343:d5928
references: 22008217
references: Biometrics. 1977 Mar;33(1):159-74
references: 843571
references: Stat Med. 2002 Jun 15;21(11):1539-58
references: 12111919
references: Circulation. 1999 Sep 7;100(10):1134-46
references: 10477542
references: Clin Pharmacokinet. 2010 Oct;49(10):661-9
references: 20818832
references: Epilepsia. 2011 Apr;52(4):826-36
references: 21320112
references: Neurology. 2010 Mar 2;74(9):755-61
references: 20194915
references: Am J Hosp Pharm. 1986 Jul;43(7):1709-14
references: 3752106
references: Br J Clin Pharmacol. 2008 Aug;66(2):327-8
references: 18507657