THE ESPRIM TRIAL - SHORT-TERM TREATMENT OF ACUTE MYOCARDIAL-INFARCTION WITH MOLSIDOMINE

Previous small clinical trials have suggested that treatment with nitr ic oxide donors in suspected myocardial infarction can reduce mortalit y by 30-35%. To confirm this finding in a large-scale trial, we compar ed molsidomine and its active metabolite linsidomine (a nitric oxide d onor) with placebo in 4017 patients with acute myocardial infarction. In our trial, patients without signs of overt heart failure (Killip II I/lV) were randomly assigned in a double-blind design within 24 h of s ymptom onset to receive linsidomine 1 mg/h intravenously for 48 h, fol lowed by 16 mg molsidomine by mouth daily for 12 days (n = 2007), or a n identical placebo (n = 2010). All other treatments could be used at the responsible physician's discretion with the exception of systemati c vasodilator treatment. The molsidomine and placebo groups showed sim ilar all-cause 35-day mortality (168 [8.4%] vs 176 [8.8%] deaths, p = 0.66), and adjustment for baseline variables in a Cox model had no eff ect. Similarly, we found no difference for long-term mortality(mean fo llow-up 13 months; 294 [14.7%] vs 285 [14.2%] deaths, p = 0.67). The t wo groups showed similar frequencies of major and minor adverse events ; only headache was significantly more common in the molsidomine group . Changes in treatment practices and the lower risk profile of our stu dy subjects than of participants in previous trials may explain the re sults. It is still not clear whether nitric oxide donors can improve s urvival in higher-risk myocardial infarction patients.