Outcome and one year follow-up of intra-arterial staphylokinase in 191 patients with peripheral arterial occlusion

Wild-type or equipotent variants of recombinant staphylokinase (rSak) were given intra-arterially (as a 2 mg bolus injection followed by an infusion o f 1 mg/h or 0.5 mg/h overnight, with concomitant heparin [1000 IU/h]) to 19 1 patients of less than 80 years (62 +/- 1 years, mean +/- SEM), with a per ipheral arterial occlusion (PAO) of less than 120 days (mean 14 +/- 1 days, median 11 days, 5 to 95 percentiles 3 to 30 days). Ninety nine patients pr esented with acute or subacute ischemia, 57 with severe claudication, 33 wi th chronic rest pain and 2 with gangrene. Occlusion occurred in 122 native arteries and in 69 grafts. Revascularization was complete in 83 percent (15 8/191), partial in 13 percent (24/191) and absent in 4 percent (7/191) afte r administration of 12 +/- 0.5 mg rSak over 14 +/- 0.7 h. Complete revascul arization of acute occlusions of popliteal or more distal arteries was less frequent (60 percent, 15/25) than of acute occlusions of more proximal nat ive arteries (95 percent, 37/39, p <0.001) or grafts (89 percent, 50/56, p = 0.005). Additional endovascular procedures were performed in 47 percent a nd subsequent elective bypass surgery in 23 percent of patients. Major blee ding occurred in 12 percent (23/191), one month mortality was 3.1 percent ( 6/191) and one year mortality was 6.9 percent (12/174). However, four patie nts (2.1 percent) had an intracranial bleeding following therapy: a 85 year old woman with severe diabetic arteriopathy, who was included in violation of the protocol, a 79 and a 74-year-old woman and a 74-year-old man, all w ith severe hypertension and limb threatening ischemia; these four patients died within two months after treatment. Amputations were performed within t he first year in 16 of 162 surviving patients (9.8 percent): in 7 percent ( 7/96) with an occluded native artery and 14 percent (9/66) with an occluded graft (p = 0.19). No significant difference in lysis rate, one month morta lity or one year amputation-free survival was observed in occlusions of rec ent onset (less than or equal to 14 days, n = 126) as compared to occlusion s of longer duration (>14 days, n = 65). Treatment was interrupted prematur ely in 4 patients because of a suspected allergic reaction. Fibrinogen leve ls remained unaffected during treatment (3.3 +/- 0.1 g/l before vs. 3.3 +/- 0.1 g/l after infusion, n = 167). In conclusion, rSak appears to be a highly effective thrombolytic agent in patients with PAO, resulting in a low one month mortality (3.1 percent) and a high one year amputation free survival (84 percent), with an acceptable incidence of major bleedings, but with occasional fatal intracranial hemorr hages.