title: Outcome and one year follow-up of intra-arterial staphylokinase in 191 patients with peripheral arterial occlusion.
abstract: Wild-type or equipotent variants of recombinant staphylokinase (rSak) were given intra-arterially (as a 2 mg bolus injection followed by an infusion of 1 mg/h or 0.5 mg/h overnight, with concomitant heparin [1000 IU/h]) to 191 patients of less than 80 years (62 +/- 1 years, mean +/- SEM), with a peripheral 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 presented with acute or subacute ischemia, 57 with severe claudication, 33 with chronic rest pain and 2 with gangrene. Occlusion occurred in 122 native arteries and in 69 grafts. Revascularization was complete in 83 percent (158/191), partial in 13 percent (24/191) and absent in 4 percent (7/191) after administration of 12 +/- 0.5 mg rSak over 14 +/- 0.7 h. Complete revascularization of acute occlusions of popliteal or more distal arteries was less frequent (60 percent, 15/25) than of acute occlusions of more proximal native 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 and subsequent elective bypass surgery in 23 percent of patients. Major bleeding 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 patients (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 with severe hypertension and limb threatening ischemia; these four patients died within two months after treatment. Amputations were performed within the 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 mortality or one year amputation-free survival was observed in occlusions of recent onset (< or =14 days, n = 126) as compared to occlusions of longer duration (>14 days, n = 65). Treatment was interrupted prematurely in 4 patients because of a suspected allergic reaction. Fibrinogen levels 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 hemorrhages.
authors.affiliation: Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Heymans
authors.forename: S
authors.initials: S
authors.lastname: Vanderschueren
authors.forename: R
authors.initials: R
authors.lastname: Verhaeghe
authors.forename: L
authors.initials: L
authors.lastname: Stockx
authors.forename: H
authors.initials: H
authors.lastname: Lacroix
authors.forename: A
authors.initials: A
authors.lastname: Nevelsteen
authors.forename: Y
authors.initials: Y
authors.lastname: Laroche
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D000368:Aged; D000671:Amputation, Surgical / Q000706:statistics & numerical data; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D001798:Blood Proteins / Q000032:analysis; D004341:Drug Evaluation; D004617:Embolism / Q000188:drug therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000188:drug therapy; D006439:Hemodynamics; D006470:Hemorrhage / Q000139:chemically induced; D006487:Hemostasis; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008666:Metalloendopeptidases / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D015996:Survival Rate; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000401:mortality; D013927:Thrombosis / Q000188:drug therapy; D016896:Treatment Outcome; D014654:Vascular Patency
chemical_list: D001798:Blood Proteins; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus