title: Epidemiologic Evaluation of Cardiovascular Risk in Patients Receiving Milnacipran, Venlafaxine, or Amitriptyline: Evidence from French Health Data.
abstract: BACKGROUND
  Milnacipran, a selective serotonin and norepinephrine reuptake inhibitor, is approved by the Food and Drug Administration for the management of fibromyalgia. It has been available for many years in several countries outside the US for the treatment of depression.
  
  
  OBJECTIVE
  To conduct population-based analyses comparing the risk of serious cardiovascular (CV) events (eg, acute myocardial infarction, stroke, congestive heart failure) associated with treatment with milnacipran compared with venlafaxine and amitriptyline, 2 other commonly prescribed drugs that also inhibit reuptake of norepinephrine and serotonin.
  
  
  METHODS
  Information from the French Thales electronic health record database from 2001 to 2007 was used. Patients with 1 or more prescriptions for milnacipran, venlafaxine, or amitriptyline; 180 or more days of continuous eligibility prior to the first prescription; and no prior CV event diagnoses during the 180-day baseline period were included. A retrospective, matched-cohort design was employed. The incidence rates of CV events between cohorts receiving milnacipran, venlafaxine, and amitriptyline were compared using unadjusted incidence rate ratio (IRR) and adjusted conditional IRR based on Poisson regression.
  
  
  RESULTS
  We identified 4452 milnacipran-venlafaxine and 3761 milnacipran-amitriptyline matched pairs. The matched cohorts had similar baseline characteristics. The unadjusted IRRs of any CV events, comparing milnacipran with venlafaxine or amitriptyline, were 1.02 (95% CI 0.73 to 1.44) and 1.30 (95% CI 0.90 to 1.89), respectively. Adjusted IRRs confirmed the statistical similarity in the CV event risk between milnacipran and venlafaxine (adjusted IRR = 1.29, 95% CI 0.76 to 2.17) or amitriptyline (adjusted IRR = 1.06, 95% CI 0.59 to 1.89).
  
  
  CONCLUSIONS
  This French population-based study found that the risk of CV events was not significantly different for patients receiving milnacipran versus those receiving venlafaxine or amitriptyline.
authors.affiliation: Philip J Mease MD, Seattle Rheumatology Associates, Swedish Medical Center, Seattle, WA pmease@nwlink.com.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.affiliation: Peter J Zimetbaum MD, Associate Professor of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Zimetbaum
authors.affiliation: Mei Sheng Duh MPH ScD, Managing Principal, Analysis Group, Inc., Boston, MA.
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
authors.affiliation: Francis Vekeman MA, Manager, Groupe d'analyse, Ltée, Montréal, Québec, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Vekeman
authors.affiliation: Annie Guérin MA, Manager, Groupe d'analyse, Ltée.
authors.forename: Annie
authors.initials: A
authors.lastname: Guérin
authors.affiliation: Mariette Boerstoel-Streefland MD MS(epi) MBA, Chief Safety Officer, Vice President Global Drug Safety, Forest Research Institute, Jersey City, NJ.
authors.forename: Mariette
authors.initials: M
authors.lastname: Boerstoel-Streefland
authors.affiliation: Wenjun Jiang MD MPH, Associate Director, Pharmacovigilance and Risk Management, Forest Research Institute.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Patrick Lefebvre MA, Vice President, Groupe d'analyse, Ltée.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lefebvre
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects*; D000328:Adult; D000639:Amitriptyline / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D003521:Cyclopropanes / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D012189:Retrospective Studies; D012306:Risk; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology; D014481:United States; D000069470:Venlafaxine Hydrochloride / Q000627:therapeutic use*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000639:Amitriptyline; D000928:Antidepressive Agents; D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride