Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
The Very Early Nimodipine Use in Stroke (VENUS) trial was designed to test the hypothesis that early treatment with nimodipine has a positive effect on survival and functional outcome after stroke. This was suggested in a previous meta-analysis on the use of nimodipine in stroke. However, in a recent Cochrane review we were unable to reproduce these positive results. This led to the early termination of VENUS after an interim analysis.


METHODS
In this randomized, double-blind, placebo-controlled trial, treatment was started by general practitioners or neurologists within 6 hours after stroke onset (oral nimodipine 30 mg QID or identical placebo, for 10 days). Main analyses included comparisons of the primary end point (poor outcome, defined as death or dependency after 3 months) and secondary end points (neurological status and blood pressure 24 hours after inclusion, mortality after 10 days, and adverse events) between treatment groups. Subgroup analyses (on final diagnosis and based on the per-protocol data set) were performed.


RESULTS
At trial termination, after inclusion of 454 patients (225 nimodipine, 229 placebo), no effect of nimodipine was found. After 3 months of follow-up, 32% (n=71) of patients in the nimodipine group had a poor outcome compared with 27% (n=62) in the placebo group (relative risk, 1.2; 95% CI, 0.9 to 1.6). A treatment effect was not found for secondary outcomes and in the subgroup analyses.


CONCLUSIONS
The results of VENUS do not support the hypothesis of a beneficial effect of early nimodipine in stroke patients.
Horn
J
J
Department of Neurology, Academic Medical Center, University of Amsterdam (Netherlands).
de Haan
R J
RJ
Vermeulen
M
M
Limburg
M
M
D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009553:Nimodipine / Q000008:administration & dosage* / Q000009:adverse effects; D015588:Observer Variation; D010291:Paresis / Q000209:etiology; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D015996:Survival Rate; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D009553:Nimodipine