V.A. Cooperative Study of antiplatelet agents in diabetic patients after amputation for gangrene: unobserved, sudden, and unexpected deaths.

We report on unobserved, sudden, and unexpected deaths that occurred in a randomized multicenter trial. The long-term effects of aspirin plus dipyridamole on major vascular outcome variables were studied in 231 non insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Depending upon the definition of sudden death used, there were 14, 22, or 17 deaths in the drug group versus 6, 6, or 3 deaths in the placebo group (p = 0.04, 0.001, or 0.001, respectively). Total deaths from atherosclerotic vascular disease or deaths from all causes did not differ in the two treatment groups. Since this finding of a secondary end point is found only after multiple analyses of the data, it must be interpreted with caution. However, it is suggested that further studies on effects of antiplatelet agents on sudden deaths should be performed.