A secondary prevention, randomized trial of suloctidil in patients with a recent history of thromboembolic stroke

Abstract

Four hundred and thirty-eight patients who had suffered a thromboembolic stroke not less than two weeks or more than four months previously, were entered into a placebo-controlled randomized clinical trial to determine whether suloctidil (200 mg t.i.d.) would influence the subsequent recurrence of stroke, the occurrence of myocardial infarction, or cardiovascular death. The two treatment groups were comparable at baseline with respect to important prognostic variables and there was good adherence to the study protocol during an average follow-up of 20 months. Significantly more patients complained of side-effects in the suloctidil group and more hepatotoxicity was also reported in the suloctidil group. Four cases of clinical hepatitis were suspected to be due to suloctidil, each of which was reversible on termination of study treatment; relative increases in SGOT and SGPT at three months in the suloctidil group were found to be mild and transient. The primary analysis of efficacy was based on the incidence of the first event of stroke, myocardial infarction or cardiovascualr death, but excluding events that occurred more than 28 days after complete withdrawal from study medication for whatever reason. Thus, the primary analysis included 38 events in the suloctidil group and 47 in the placebo group (p = 0.17) representing a risk reduction of 24%. If total mortality is substituted for cardiovascular death, the corresponding figures are 47 in the suloctidil group and 58 in the placebo group (p = 0.08). There were interesting differences seen in an analysis of cardiovascular mortality alone (p = 0.06), and total mortality alone (p = 0.04), and specifically in terms of cardiac death where there were 15 deaths in the placebo group and only five in the suloctidil group. A total of 31 patients in the suloctidil group had a recurrence of stroke, fatal or non-fatal, compared with only 28 in the placebo group. As might be expected, the absolute differences in outcomes in the two treatment groups were similar, but statistically less impressive, when analyzed on an intention-to-treat basis. Thus, there is no evidence of benefit of suloctidil in preventing the recurrence of stroke, but in view of the observed difference in cardiac death further studies with suloctidil may be warranted. © 1985 American Heart Association, Inc.