Cardiology · 1991
SOLVD Treatment Trial
Studies of Left Ventricular Dysfunction (Treatment Trial)
By the late 1980s, the CONSENSUS trial had established that enalapril reduced mortality in patients with the most severe heart failure, NYHA class IV disease. That left a pressing clinical question unanswered: did the same neurohormonal blockade help the far larger population of patients with symptomatic but less advanced disease? These were the patients filling outpatient cardiology practices, functional but declining, with ejection fractions below 35% and no reliable therapy beyond digoxin and diuretics.
The Studies of Left Ventricular Dysfunction Treatment Trial enrolled 2,569 patients across multiple North American and European sites. All had symptomatic heart failure and an ejection fraction at or below 35%; they were randomized to enalapril or placebo on top of whatever standard care their physicians were already providing. Follow-up averaged about 41 months, long enough to accumulate meaningful mortality data across the full severity spectrum.
Enalapril cut all-cause mortality by 16% and the combined endpoint of death or hospitalization for heart failure by 26%. The absolute mortality reduction was modest in any single patient but consistent across age, sex, and ejection fraction subgroups. Adverse effects were manageable: the drug caused more dizziness and elevated creatinine but was not associated with excess discontinuation in the enalapril arm.
The trial's companion piece, SOLVD Prevention, enrolled patients with low ejection fraction but no symptoms yet and showed enalapril delayed the onset of overt heart failure in that group. Together, the two SOLVD arms sketched the entire arc of the disease and showed that neurohormonal blockade was useful from preclinical dysfunction through symptomatic failure.
When the SOLVD Treatment results appeared in the New England Journal of Medicine in 1991, cardiologists had, for the first time, mortality evidence extending ACE inhibitor therapy to the mainstream of heart failure patients. Guidelines in the United States and Europe moved ACE inhibitors into first-line recommendations for systolic heart failure across all symptomatic severity classes, a position they have held ever since. The 16% mortality reduction in a population that had previously received nothing more than symptom control represented a concrete survival gain for millions of patients annually.
Key People
- The SOLVD Investigators — Multinational group that designed and ran the trial
- Milton Packer — Key contributor to heart failure trial methodology in this era
- Jay Cohn — University of Minnesota cardiologist and heart failure trialist instrumental to SOLVD design
N Engl J Med. 1991;325(5):293-302.