title: Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review.
abstract: OBJECTIVE
  Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS.
  
  
  METHODS
  We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
  
  
  RESULTS
  Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] -3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5-48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6-68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%-47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03-10.37]).
  
  
  CONCLUSIONS
  Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS.
authors.affiliation: From the Internal Medicine Department (A.I., C.G.M., M.M., H.N.C.), Hospital Alemán, Buenos Aires, Argentina; and Department of Clinical Epidemiology and Biostatistics (G.G.), McMaster University, Hamilton, Canada. ariel.izcovich@gmail.com.
authors.forename: Ariel
authors.initials: A
authors.lastname: Izcovich
authors.affiliation: From the Internal Medicine Department (A.I., C.G.M., M.M., H.N.C.), Hospital Alemán, Buenos Aires, Argentina; and Department of Clinical Epidemiology and Biostatistics (G.G.), McMaster University, Hamilton, Canada.
authors.forename: Carlos
authors.initials: C
authors.lastname: González Malla
authors.affiliation: From the Internal Medicine Department (A.I., C.G.M., M.M., H.N.C.), Hospital Alemán, Buenos Aires, Argentina; and Department of Clinical Epidemiology and Biostatistics (G.G.), McMaster University, Hamilton, Canada.
authors.forename: Matias
authors.initials: M
authors.lastname: Manzotti
authors.affiliation: From the Internal Medicine Department (A.I., C.G.M., M.M., H.N.C.), Hospital Alemán, Buenos Aires, Argentina; and Department of Clinical Epidemiology and Biostatistics (G.G.), McMaster University, Hamilton, Canada.
authors.forename: Hugo Norberto
authors.initials: HN
authors.lastname: Catalano
authors.affiliation: From the Internal Medicine Department (A.I., C.G.M., M.M., H.N.C.), Hospital Alemán, Buenos Aires, Argentina; and Department of Clinical Epidemiology and Biostatistics (G.G.), McMaster University, Hamilton, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
mesh_terms: D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy*; D008879:Midodrine / Q000627:therapeutic use*; D011788:Quality of Life; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D055502:Secondary Prevention; D013575:Syncope / Q000188:drug therapy*
chemical_list: D008879:Midodrine