Withdrawal from treatment in the Syst-Eur Trial.
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A total of 135 patients (6%) were withdrawn by the investigators from placebo treatment because their blood pressure was too high, and, similarly, 36 (1.6%) through patient initiation.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 Very few patients were withdrawn from the trial because of the adverse effects of treatment.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The numbers withdrawn from the trial for adverse treatment consequences were small in comparison to the cardiovascular benefits.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.
Bulpitt
Christopher J
CJ
Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK. c.bulpitt@ic.ac.uk
Beckett
Nigel S
NS
Fletcher
Astrid E
AE
Thijs
Lutgarde
L
Staessen
Jan A
JA
Dumitrascu
Dan L
DL
Forette
Francoise
F
Leonetti
Gastone
G
Nachev
Choudomir
C
Tuomilehto
Jaakko
J
Fagard
Robert H
RH
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
D000959:Antihypertensive Agents