SOLVD (Studies of Left Ventricular Dysfunction) Enalapril vs placebo in 6,794 patients Ejection fraction < 35% End points include: Delaying the progression of heart failure Improving signs and symptoms Reducing mortality Treatment arm - 2,568 symptomatic class II-III patients most on digitalis and diuretics Prevention arm - 4,226 asymptomatic class I-II patients, most on no concomitant therapy N Engl J Med 1991:325:293-302

SOLVD Treatment Trial All Cause Mortality 16% Risk Reduction p = 0.0036 N Engl J Med 1991;325:293-302

Benefits of Enalapril Patients: Symptomatic HF patients with LVD (EF < 35%) Increased Survival 32% at 3 months 28% at 6 months 21% at 12 months 18% at 24 months 12% at 36 months 12% at 48 months 11% reduction of overall mortality at end of study (P=0.0036) The SOLVD Investigators, N Engl J Med. 1991;325:293

SOLVD Treatment Trial Mortality or Hospitalization for CHF 26% Risk Reduction p<0.0001 N Engl J Med 1991;325:293-302

SOLVD Treatment-Enalapril Symptomatic HF Patients with LVD (EF < 35%) (NYHA Class II-III) 30% Reduction p<0.001 971 683 Number of Hospitalizations Due to Heart failure The SOLVD Investigators, N Engl J Med, 1991

SOLVD Treatment-Enalapril Symptomatic HF Patients with LVD (EF < 35%) (NYHA Class II-III) 33% Reduction p<0.001 234 157 Number of Readmissions for Heart failure The SOLVD Investigators, N Engl J Med, 1991

SOLVD Treatment Trial Implications: Treating 1,000 patients for 3 years Prevents about 50 deaths Prevents about 350 hospitalizations

Benefits of Enalapril Patients: Symptomatic HF patients with LVD (EF < 35%) Decreased hospitalizations 48% at 3 months 51% at 6 months 46% at 12 months 23% at 24 months 28% at 36 months 30% reduction of overall hospitalization at end of study (P<0.0001) Convenient once - or twice - daily dosing The SOLVD Investigators, N Engl J Med. 1991;325:293

SOLVD Treatment Trial Conclusions Hospitalizations: Risk reduced by 20% (p<0.001) Significant reduction in CHF hospitalization by 1/3 (p<0.0001) Sustained benefit over 4 years N Engl J Med 1991;325:293-302

SOLVD Prevention Trial All Cause Mortality Risk Reduction 8% P=0.30 N Engl J Med 1992;327:685-91

SOLVD Prevention Trial Death or Development of CHF Risk Reduction 29% p<0.001 N Engl J Med 1992;327:685-91

SOLVD Prevention Trial First Hospitalization for CHF Risk Reduction 36% p<0.001 N Engl J Med 1992;327:685-91

SOLVD Prevention Trial N Engl J Med 1992;327:685-91

SOLVD Prevention- Enalapril Asymptomatic HF Patients w/ LVD (EF < 35%) (NYHA Class I-II) 32% Fewer First Hospitalizations p<0.001 273 184 Number of First Hospitalizations for Heart Failure The SOLVD Investigators, N Engl J Med, 1992.

SOLVD Prevention Trial Morbidity and Combined Outcomes

Enalapril - Dosing