Multicenter Double-Blind Study of Ticlopidine in the Treatment of Intermittent Claudication and the Prevention of its Complications

Abstract

In this multicenter trial 169 patients with chronic intermittent claudication due to obstructive peripheral vascular disease were randomized in a double-blind fashion into two parallel groups receiving either 250 mg ticlopidine or placebo, twice daily. At entry, the two groups (83 ticlopidine, 86 placebo) were well matched for the major clinical features apart from an excess of women in the ticlopidine group. At six months, 167 patients were alive, 2 having died of malignant disease (1 from each group). At this stage, 39 patients from the ticlopidine group and 29 from the placebo group (p = 0.04) had increased their walking distance by more than 50% of baseline values. For the groups as a whole pain-free and total walking distance were greater in the ticlopidine group than in the placebo group (194 vs 124 meters, p = 0.03 and 236 vs 170 meters, p = 0.04, respectively). Two patients from the ticlopidine group vs 9 patients from the placebo group (p = 0.03) developed significant cardiovascular events during the study. These results indicate that ticlopidine has a beneficial effect both in the treatment of the symptoms and the prevention of vascular complications in patients with intermittent claudication.

Prasugrel, a Platelet P2Y 12 Receptor Antagonist, Improves Abnormal Gait in a Novel Murine Model of Thrombotic Hindlimb Ischemia

“…However, limb ischemia without severe limb lesions observed in our model might be considered to reflect the situation in patients with mild PAD 5. Furthermore, the impact of P2Y 12 deficiency or pharmacological antagonism in the present model were similar to clinical observations on the efficacy of ticlopidine in patients with intermittent claudication 8, 9. Therefore, we believe our model mimics at least acute limb ischemia in patients with mild PAD.…”

“…While P2Y 12 antagonists appear to be efficacious in reducing cardiovascular events in patients with PAD, their efficacy in controlling intermittent claudication in patients with PAD is less clear. Ticlopidine, the first‐generation thienopyridyl P2Y 12 antagonist, demonstrated beneficial effects on the improvement of limb functions8, 9 and the prevention of vascular complications8, 11 in patients with intermittent claudication. However, other studies reported that ticlopidine and clopidogrel, the second‐generation thienopyridine, had no clear beneficial effects on symptoms in PAD 7, 10, 12.…”

“…On the basis of this evidence, treatments with antiplatelet therapy for the prevention of cardiovascular events in PAD patients have been recommended 5, 6. Treatment for limb complications of PAD, including intermittent claudication, ischemic pain, or ischemic ulceration, is also a clinical goal; however, the efficacy of P2Y 12 inhibition on the progression of ischemic symptoms as the primary end point in PAD patients has not been consistent 7, 8, 9, 10, 11, 12. Further studies are therefore required to better understand the role for P2Y 12 inhibition in controlling ischemic limb complications in patients with PAD.…”

Third Asian PAD Workshop

“…15) Cilostazol, beraprost and ticlopidine have been studied for their ability to prevent cardiovascular events in PAD patients. 14,15) Cilostazol did not prevent death and cardiovascular events. There was no significant difference in all death and cardiovascular events between the placebo and cilostazol groups.…”

“…In a multicenter trial of patients with chronic intermittent claudication ticlopidine had a beneficial effect both in the treatment of the symptoms and the prevention of vascular complications in patients with intermittent claudication. 14) In another study patients with intermittent claudication were randomly allocated to receive the antiplatelet agent ticlopidine (250 mg twice per day) or an identical placebo. Long-term treatment with ticlopidine improved walking ability and ankle systolic blood pressure in patients with claudication.…”