The Cooperative North Scandinavian ENalapril SUrvival Study (CONSENSUS, 1988) and the Studies Of Left Ventricular Dysfunction (SOLVD) recorded a 30% decrease in hospitalizations after adding enalapril 20 mg/day to the conventional therapy of heart failure patients. In the Survival And Ventricular Enlargement (SAVE) study, captopril 150 mg decreased hospitalizations by 22% in patients with poor ejection fractions, but no heart failure symptoms.
Reviewing age-adjusted heart failure hospitalization trends and angiotensin-converting enzyme (ACE) inhibitor prescribing rates in the Netherlands from 1980 to 1999, Mosterd et al found a steady increase in hospitalizations in the 1980s, peaking in the 1990s at the point at which ACE inhibitor use began to rise sharply, prescription rates more than doubled between 1990 and 1999. One explanation for the end in the increase in hospitalizations is the improvement in therapy. ACE inhibitors lower mortality and readmission in heart failure and/or left ventricular dysfunction, and they lower cardiovascular events, including heart failure, in patients at increased cardiovascular risk.
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As antihypertensives, they also help to prevent heart failure, or at least postpone its onset. The stabilization of hospitalization rates, decreased length of stay, and decreased inpatient fatality rates were strikingly similar to Scottish data covering the same period.
Mosterd et al found that primary hypertension was the predominant indication for ACE inhibition (65%). Heart failure and ischemic heart disease accounted for 9.4%. ACE inhibitors were the second most frequently prescribed drugs in heart failure (30. 7%) after diuretics, followed by digoxin (14.5%).
Recent surveys indicate that only 40% to 70% of heart failure patients receive ACE-inhibitor therapy and that the daily doses are much lower than those in the clinical trials. In their retrospective study, Luzier et al found that only 22% of the patients on ACE-inhibitor therapy received the recommended dose of >20 mg/day enalapril or equivalent, and that 41% received <5 mg/day. Doses <5 mg enalapril did not lower readmission rates, whereas doses >10 mg enalapril lowered 90-day readmission rates by 28%.
The Assessment of Treatment with Lisinopril And Survival (ATLAS) trial (1999) confirmed that high doses of lisinopril (>30 mg/day) improved outcome and decreased hospitalization vs low doses (<5 mg/day); it showed that optimized ACE inhibition significantly lowered readmission rates and care costs in a heart failure management program.