Circulation, Vol 88, 492-501, Copyright © 1993 by American Heart Association
BM Massie, MR Berk, SC Brozena, U Elkayam, JF Plehn, ML Kukin, M Packer, BE Murphy, GW Neuberg and RM Steingart
BACKGROUND. Angiotensin converting enzyme inhibitors, diuretics, and
digoxin are each effective in treating congestive heart failure, but many
patients remain symptom-limited on all three medications. This trial was
designed to determine whether the addition of oral flosequinan, a new
direct-acting arterial and venous vasodilator with possible dose-dependent
positive inotropic effects, improves exercise tolerance and quality of life
in such patients. METHODS AND RESULTS. In a randomized, double-blind
multicenter trial, 322 patients with predominantly New York Heart
Association class II or III congestive heart failure and left ventricular
ejection fractions of 35% or less, who were stabilized on a diuretic,
angiotensin converting enzyme inhibitor, and digoxin, were treated with 100
mg flosequinan once daily, 75 mg flosequinan twice daily, or matching
placebo. Efficacy was evaluated with serial measurements of treadmill
exercise time, responses to the Minnesota Living With Heart Failure
Questionnaire (LWHF), and clinical assessments during a baseline phase and
a 16-week treatment period. After 16 weeks, 100 mg flosequinan once daily
produced a significant increment in median exercise time (64 seconds at 16
weeks) compared with placebo (5 seconds), whereas the higher-dose
flosequinan group did not show a statistically significant increase.
Flosequinan (100 mg once daily) also improved the overall LWHF score
significantly compared with placebo; both active therapies decreased the
physical component, but 75 mg flosequinan twice daily was associated with a
trend toward worsening of the emotional component. Most clinical
assessments tended to improve on active therapy. CONCLUSIONS. These results
indicate that additional symptomatic benefit can be attained by adding
flosequinan to a therapeutic regimen already including a converting enzyme
inhibitor. Because in the future most patients will fall into this
category, flosequinan is a potential adjunctive agent in the management of
severe congestive heart failure. However, because recent evidence indicates
that the flosequinan dose studied in the present trial has an adverse
effect on survival, the benefit-to-risk ratio must be assessed in
individual patients.
ARTICLES
Can further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET)
VAMC, Cardiology Section, San Francisco, CA 94121.
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