title: Withdrawal from treatment in the Syst-Eur Trial.
abstract: OBJECTIVE
  To investigate the reasons for withdrawal from double-blind randomized trials, and the reasons for changing treatment within a randomized therapeutic group.
  
  
  METHODS
  The Syst-Eur trial, in which 4695 older patients with systolic hypertension were randomized to active or placebo treatment.
  
  
  METHODS
  The reasons for withdrawal from the trial were examined, both for patient-initiated and investigator-initiated withdrawals. In addition, the reasons for stopping the first-line treatment (nitrendipine), the second-line treatments (enalapril and hydrochlorothiazide) and the corresponding placebos, were determined.
  
  
  RESULTS
  A total of 135 patients (6%) were withdrawn by the investigators from placebo treatment because their blood pressure was too high, and, similarly, 36 (1.6%) through patient initiation. The corresponding results for the actively treated patients were 14 (0.6%) and 7 (0.3%). Very few patients were withdrawn from the trial because of the adverse effects of treatment. However, 39 (4%) stopped taking active nitrendipine because of ankle oedema, compared with 4 (0.5%) on placebo. Similarly, 28 versus three stopped due to flushing. Forty-one (10%) stopped taking enalapril because of cough, against eight (2%) for enalapril placebo. In all, 15.0% stopped active nitrendipine, 20.2% enalapril and 6.3% hydrochlorothiazide, versus placebo 7.1, 9.1 and 5.1%.
  
  
  CONCLUSIONS
  The numbers withdrawn from the trial for adverse treatment consequences were small in comparison to the cardiovascular benefits. Nevertheless the numbers stopping individual treatments were higher than expected.
authors.affiliation: Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK. c.bulpitt@ic.ac.uk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bulpitt
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Beckett
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Fletcher
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
authors.forename: Dan L
authors.initials: DL
authors.lastname: Dumitrascu
authors.forename: Francoise
authors.initials: F
authors.lastname: Forette
authors.forename: Gastone
authors.initials: G
authors.lastname: Leonetti
authors.forename: Choudomir
authors.initials: C
authors.lastname: Nachev
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Robert H
authors.initials: RH
authors.lastname: Fagard
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D023381:Endpoint Determination; D005060:Europe / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D013997:Time Factors; D017211:Treatment Failure; D028761:Withholding Treatment
chemical_list: D000959:Antihypertensive Agents