The effect of supervised exercise and cilostazol on coagulation and fibrinolysis in intermittent claudication: A randomized controlled trial

Background

The prothrombotic, hypofibrinolytic state that develops in patients with intermittent claudication (IC) upon walking due to ischemia-reperfusion injury (IRI) of the leg muscles may contribute to the high incidence of life- and limb-threatening thrombotic events observed in this patient group. Treatments, such as angioplasty, that obtund the IRI also ameliorate the procoagulant diathesis. The effect on this diathesis of supervised exercise and cilostazol, both of which provide symptomatic benefit in IC, but without significantly obtunding IRI, is unknown.

Methods

Thirty-four patients (27 men and 7 women; median age, 67 years; range, 63-72 years) were randomized to receive best medical therapy (BMT) plus supervised exercise (n = 9), BMT plus cilostazol (n = 9), BMT plus supervised exercise plus cilostazol (n = 7), or BMT alone (n = 9) in a 2 × 2 factorial design. Thrombin-antithrombin complex and prothrombin fragments 1 and 2, both markers of thrombin generation; plasminogen activator inhibitor antigen and tissue plasminogen activator antigen, both markers of fibrinolysis; ankle-brachial pressure index (ABPI); and initial and absolute claudication distance (ACD) were measured at baseline and then 3 and 6 months after randomization.

Results

At 6 months, when compared with receiving BMT only, supervised exercise and cilostazol resulted in improvements in ABPI of 18% and 13% and in ACD of 40% and 64%, respectively. The effects on ABPI and ACD of combining supervised exercise and cilostazol were additive. Supervised exercise, cilostazol, and supervised exercise combined with cilostazol had no significant effect on any of the four hemostatic markers.

Conclusions

Treatment of IC by supervised exercise or cilostazol results in significant improvements in ABPI and ACD but has no demonstrable effect on the prothrombotic diathesis. This suggests that supervised exercise and cilostazol, unlike angioplasty, are unlikely to have a long-term beneficial effect on the thrombotic risks faced by these patients.