THE EFFECT OF A COMBINED ADMINISTRATION OF RIDOGREL AND KETANSERIN INPATIENTS WITH INTERMITTENT CLAUDICATION

After a 1-month placebo run-in phase, 27 patients with proven peripher al arterial obstructive disease participated in a double blind placebo controlled study and were divided in 3 groups, receiving either place bo, ridogrel 300 mg b.i.d. (a combined thromboxane synthase and recept or blocking agent) or a combination of ridogrel 300 mg b.i.d. and keta nserin 20 mg t.i.d. (a 5-HT2 serotonergic receptor antagonist) for a p eriod of 1 month. In both active treatment groups, serum levels of thr omboxane B2 decreased significantly to 3% of baseline. The levels of 6 -keto-prostaglandin F1alpha and prostaglandin F2alpha increased two- t o three-fold and levels of prostaglandin E2 6 times. Platelet aggregat ion induced by collagen and by U 46619, a thromboxane A2 mimetic, were significantly inhibited by both treatment regimen. Template bleeding times were significantly prolonged but plasma fibrinogen levels and th e activated partial thromboplastin time were not affected with the act ive treatments. No such changes were seen with placebo. An inhibition of the serotonin-induced platelet aggregation was only seen in the ket anserin-treated group. In a 3-month open follow-up period during combi ned treatment with ridogrel and ketanserin in 22 patients, the effects on platelet function and prostanoids were maintained. The total durat ion of the walking distance on a treadmill improved significantly from 323+/-53 seconds to 399+/-48 seconds and the onset of claudication pa in improved significantly from 121+/-29 seconds to 212+/-44 seconds, w hereas the maximal drop of the postexercise ankle/arm pressure gradien t markedly and significantly improved from a control value of 0.38+/-0 .05 to 0.51+/-0.05. These findings suggest that a combination of ridog rel and ketanserin may be of therapeutic value in the treatment of int ermittent claudication.