Crataegus extract WS®1442 in patients with congestive heart failure class NYHA II-III: The SPICE trial

WS®1442 is registered for treatment of early stages of congestive heart failure (CHF) in several countries, e.g. Germany. As there was no study available regarding efficacy and safety of WS®1442 in more severely impaired patients already treated with optimal therapy, SPICE (Survival and Prognosis: Investigation on Crataegus Extract WS®1442) was performed. SPICE is a double-blind mortality trial conducted in 156 centres in 13 European countries. Patients were eligible if their left ventricular function was markedly impaired (WMI≤1.2). These patients already receiving optimal pharmacological therapy (83% ACE-inhibitors, 64% β-blockers, 56% glycosides, 39% spironolactone, 85% diuretics) were randomised to WS®1442 or placebo. Treatment duration was 2 years; primary endpoint was the time until first cardiac event (sudden cardiac death (SCD), death due to progressive heart failure, myocardial infarction, hospitalization; FCE). 2681 patients (mean age 60yrs, 84% males, 44% NYHAIII, mean LVEF 24%) were randomised and evaluated. At all times, WS®1442 was superior to placebo regarding FCE, but without reaching statistical significance. For the first 18 months of WS®1442 treatment, deaths due to cardiac cause were reduced significantly (–20%; p=0.046) and WS®1442 postponed cardiac deaths by four months. This effect was even more pronounced in patients with LVEF≥25% (–33% reduction; p=0.044) and also holds true for total mortality and SCD up to 24 months. In conclusion, the study confirms the safety of WS®1442 in CHF patients with a mean LVEF of 24% and being treated with optimal pharmacological therapy. More important, WS®1442 may postpone deaths due to cardiac cause in this patient population.