Low-dose iloprost infusions compared to the standard dose in patients with peripheral arterial occlusive disease Fontaine stage IV. DAWID Study Group.
BACKGROUND
Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/min has been shown in patients with PAOD III/IV to significantly improve healing of trophic lesions, relief of rest pain, and reduce the rate of major amputation or death at 6 months as compared to placebo. The effect is considered related to improvement of the microcirculation. The aim of the present trial was to identify an optimum dose regarding treatment response and tolerability, by studying 4 doses of 25, 50, 75 and 100 micrograms iloprost daily.


METHODS
302 patients with PAOD IV were randomised via a double-blind fashion to one of the 4 doses. The primary endpoint was the responder rate at end of treatment. Responders were defined as patients with very good or good global efficacy, as judged by lesion healing and pain relief. Side effects were documented and a pre-defined benefit/risk index was calculated.


RESULTS
No dose-dependency of iloprost regarding primary or secondary endpoints was observed. The rate of responders ranged between 48.7-53.5%. Side effects, mainly related to vasodilation, increased dose-dependently (p < 0.001, chi 2-test), with a significant decrease of the benefit/risk index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA). Responders had a better outcome at 6 months than non-responders (2.6 fold higher rate of major amputation or death; life table analysis).


CONCLUSIONS
It is concluded that iloprost should be titrated to the optimum rather than maximum tolerated dose, since a higher incidence of side effects not associated with an increased treatment response was observed at higher doses.
Beischer
W
W
Klinische Entwicklung Herz-Kreislauf und Zentrales Nervensystem, Schering AG, Berlin.
Dembski
J C
JC
Gruss
J D
JD
Hofgärtner
F
F
Horsch
A
A
Horsch
S
S
Kuhlmann
H W
HW
Loose
D A
DA
Mietaschk
A
A
Schwilden
E D
ED
Spengel
F
F
Spitzer
W
W
Staben
P
P
Stallkamp
B
B
Stürzebecher
C S
CS
Tokhi
M
M
von Bilderling
P
P
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000145:classification / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007511:Ischemia / Q000188:drug therapy; D007866:Leg / Q000098:blood supply; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D014665:Vasodilator Agents; D016285:Iloprost