NIMODIPINE NEUROPROTECTION IN CARDIAC-VALVE REPLACEMENT - REPORT OF AN EARLY TERMINATED TRIAL

Background We conducted a double-blind, randomized clinical trial in p atients undergoing cardiac valve replacement to determine whether nimo dipine, a dihydropyridine calcium antagonist, reduced the risk of new neurological, neuro-ophthalmologic, or neuropsychological deficits-com mon complications associated with cardiac surgery-1 week after surgery . Methods and Results Enrollment for a total of 400 patients started i n May 1992 and was stopped in September 1994, with 150 patients random ized to the study. Nimodipine was given to the patients during the per ioperative period. Patients underwent examinations before surgery and at approximately 1 week, 1 month, and 6 months after surgery. Major ad verse events, including deaths and strokes, were monitored monthly. Th e trial was terminated early because of both an unexpected disparity i n death rates between groups and a lack of evidence of a beneficial ef fect of nimodipine. New deficits were observed in 72% of the placebo g roup 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) c ompared 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 pa tients with major bleeding died compared with 3 deaths (2.2%) among th e 136 patients without major bleeding. Conclusions Our findings add to the growing evidence that calcium antagonists have a prohemorrhagic e ffect in some patients and suggest that nimodipine use should be restr icted perioperatively in patients scheduled for cardiac valve replacem ent.