INTRAVENOUS NIMODIPINE WEST-EUROPEAN STROKE TRIAL (INWEST) OF NIMODIPINE IN THE TREATMENT OF ACUTE ISCHEMIC STROKE

A randomised, double-blind, placebo-controlled trial of intravenous nimodipine was conducted in 295 patients with acute ischaemic stroke. Nimodipine was given as an intravenous infusion of 1 or 2 mg/h for 5 days followed by an oral dose of 120 mg daily for a total treatment period of 21 days. Patients with a clinical diagnosis of ischaemic stroke in the carotid artery territory within 24 h entered the study at 34 centres, involving 1 I European countries: 100 were randomly assigned to placebo, 101 to nimodipine with an initial intravenous dose of 1 mg/h and 94 patients to an initial dose of 2 mg/h. The trial, initially aiming at a patient inclusion of 600, was terminated because of concerns arising from safety monitoring. Primary efficacy variables were neurological outcome according to the Orgogozo scale and functional outcome according to the Barthel scale at day 21. There were apparent differences between the groups in neurological and functional outcome with a better outcome in the placebo group. The differences between the placebo group and the 2-mg/h group were statistically significant (p = 0.0005 for the Orgogozo scale and p = 0.0033 for the Barthel scale). The differences were even more pronounced at the final follow-up at 24 weeks (p = 0.0001 and p = 0.0002, respectively). There were no statistically significant differences in mortality between the groups. There were statistically significant differences between the groups regarding the effect of the first few days of intravenous treatment on systolic and diastolic blood pressure with the most pronounced reduction in the 2-mg/h nimodipine treatment group at day 2 (p = 0.0001). An explorative analysis indicated a correlation between diastolic blood pressure reduction in the nimodipine-treated groups and unfavourable neurological outcome (p = 0.0005). A potential neuroprotective effect of nimodipine by preventing calcium overload in ischaemic neurons may thus have been outweighed by detrimental haemodynamic effects in the ischaemic area.