Flosequinan in chronic heart failure: how is exercise capacity improved?
OBJECTIVE
Diuretics, angiotensin converting enzyme inhibitors and digoxin have become "standard" triple therapy for many patients with chronic cardiac failure. Flosequinan increases exercise duration and improves symptoms when added to standard triple therapy. Despite intensive study, the clinical pharmacology of flosequinan remains uncertain.


METHODS
The University Hospital of Wales, a Regional Cardiac Centre.


METHODS
Twenty four patients with chronic heart failure who remained symptomatic despite standard therapy including ACE inhibitors.


METHODS
A double-blind placebo-controlled parallel group study of 100 mg daily of flosequinan. We measured changes in exercise duration using cardiorespiratory exercise testing and changes in large artery distensibility using Doppler ultrasound.


RESULTS
Exercise duration after 8 weeks flosequinan treatment was significantly greater than following placebo treatment. The flosequinan-related increase in exercise duration (+14%) was associated with a significant reduction in VE/VCO2 slope (-16%). Brachial-radial pulse wave velocities were unaltered by flosequinan treatment.


CONCLUSIONS
Our results confirm that flosequinan improves exercise duration in patients with chronic heart failure. They suggest that this observed beneficial effect is independent of any change in large artery distensibility and that in the presence of ACE inhibitors, this improvement may be independent of any vasodilating action of flosequinan. Although this study confirms the beneficial symptomatic effects of flosequinan in chronic cardiac failure, clinical trials have subsequently demonstrated an overall increase in mortality in patients treated with 100 mg flosequinan daily. This has resulted in the withdrawal of flosequinan from routine clinical use.
Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
A P
AP
Banning
M W
MW
Ramsey
E A
EA
Jones
W
W
Evans
G
G
Carolan
C H
CH
Jones
A H
AH
Henderson
D000328:Adult; D000368:Aged; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010807:Physical Endurance; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D011804:Quinolines; D014665:Vasodilator Agents; C047316:flosequinan