Nimodipine neuroprotection in cardiac valve replacement - Report of an early terminated trial

Background We conducted a double-blind, randomized clinical trial in patients undergoing cardiac valve replacement to determine whether nimodipine, a dihydropyridine calcium antagonist, reduced the risk of new neurological, neuro-ophthalmologic, or neuropsychological deficits-common complications associated with cardiac surgery-1 week after surgery. Methods and Results Enrollment for a total of 400 patients started in May 1992 and was stopped in September 1994, with 150 patients randomized to the study. Nimodipine was given to the patients during the perioperative period. Patients underwent examinations before surgery and at approximately 1 week, 1 month, and 6 months after surgery. Major adverse events, including deaths and strokes, were monitored monthly. The trial was terminated early because of both an unexpected disparity in death rates between groups and a lack of evidence of a beneficial effect of nimodipine. New deficits were observed in 72% of the placebo group versus 77% of the nimodipine group (P=.55). In the 6-month follow-up period, 8 deaths (10.7%) occurred in the nimodipine group (n=75) compared with 1 death (1.3%) in the placebo group (n=74) (P=.02). Major bleeding occurred in 10 patients in the nimodipine group versus 3 in the placebo group (13.3% versus 4.1%; P=.04). Six (46.2%) of the 13 patients with major bleeding died compared with 3 deaths (2.2%) among the 136 patients without major bleeding. Conclusions Our findings add to the growing evidence that calcium antagonists have a prohemorrhagic effect in some patients and suggest that nimodipine use should be restricted perioperatively in patients scheduled for cardiac valve replacement.