Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.

BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.

What is the cost of nephrotoxicity associated with aminoglycosides?

We measured the economic impact of aminoglycoside-associated nephrotoxicity in a nested case-control study at six Philadelphia area hospitals. From the charts of 1756 patients who received aminoglycosides and met entry criteria, we collected data on patient demographics, clinical characteristics, and resource utilization for all patients with nephrotoxicity and for a sample of patients without nephrotoxicity. Of the 1756 patients, 129 (7.3%) developed aminoglycoside-associated nephrotoxicity. The component costs of nephrotoxicity were calculated by hospital accounting methods; room and board costs were enumerated with per diem rates. The additional cost of hospital ancillary services per case of nephrotoxicity was $446 (p less than 0.001); the additional cost of hospital stay was $825 for additional routine days (2.74 days) (p less than 0.02) and $1152 for intensive care days (1.50 days) (p less than 0.01). Additional consultations were $78 per patient. Therefore, the mean total additional cost of aminoglycoside-associated nephrotoxicity was $2501. The average additional cost per patient receiving aminoglycosides was $183.