SOLVD 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 of 35% or less.

The Studies of Left Ventricular Dysfunction Treatment Trial enrolled 2,569 patients across multiple North American and European sites. All had chronic heart failure and an ejection fraction of 35% or less, and about 90 percent were in NYHA classes II and III; 1,285 were randomized, double-blind, to enalapril at 2.5 to 20 mg a day and 1,284 to placebo, on top of their existing treatment. Follow-up averaged about 41 months, long enough to accumulate meaningful mortality data across the full severity spectrum.

There were 452 deaths on enalapril (35.2 percent) and 510 on placebo (39.7 percent), a 16% reduction in risk, and the combined endpoint of death or hospitalization for worsening heart failure fell by 26%. The largest reduction was in deaths from progressive heart failure (209 against 251), with little effect on deaths from arrhythmia without pump failure.

The companion SOLVD Prevention trial, reported in 1992, enrolled patients with low ejection fraction but no symptoms; enalapril did not significantly reduce deaths (313 against 334) but lowered the combined total of deaths and new heart failure (630 against 818). 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 treatment trial's report was published on August 1, 1991.