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Thrombolysis had benefit similar to that of surgery for acute arterial leg occlusion but had more hemorrhagic complications

ACP J Club. 1998 Sep-Oct;129:38. doi:10.7326/ACPJC-1998-129-2-038

Related Content in the Archives
• Correction: Thrombolysis had benefit similar to that of surgery for acute arterial leg occlusion but had more hemorrhagic complications

Source Citation

Ouriel K, Veith FJ, Sasahara AA, for the Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. N Engl J Med. 1998 Apr 16;338:1105-11.



Among patients with acute peripheral arterial occlusion of the legs, is initial thrombolysis with catheter-administered urokinase as efficacious and safe as immediate open surgery?


Multicenter, randomized, controlled trial (Thrombolysis or Peripheral Arterial Surgery Trial) with 6- and 12-month follow-up.


113 centers in North America and Europe.


544 patients (mean age 64.7 y, 67% men, 79% white) who had acute thrombotic or embolic leg occlusion within 14 days of randomization and met guidelines for reversible limb-threatening ischemia, were > 17 years of age, and were medically eligible for thrombolytic or surgical intervention. Pregnant or possibly pregnant women were excluded.


Randomization was stratified by type of graft (native arterial segment or bypass). 272 patients were allocated to urokinase, 4000 IU/min, infused through an intra-arterial catheter for the first 4 hours and 2000 IU/min thereafter. Infusions were stopped when lysis was complete, arteriography showed no further progress, or 48 hours had passed. Successful urokinase therapy was followed by surgical or endovascular treatment as needed. 272 patients were allocated to vascular surgery.

Main outcome measures

Main outcomes included amputation-free survival at 6 and 12 months and major hemorrhagic complications.

Main results

Analysis was by intention to treat. No differences existed for 6- or 12-month amputation-free survival (P = 0.43 and P = 0.23, respectively) (Table) or mortality (16.0% for urokinase vs 12.3% for surgery, P = 0.22, at 6 mo; 20.0% for urokinase vs 17.0% for surgery, P = 0.39, at 12 mo). Among those who actually received their assigned treatment (n = 511), more patients in the thrombolysis group had major hemorrhagic complications (P = 0.005) (Table).


In patients with acute peripheral arterial occlusion of the legs, initial thrombolysis with catheter-administered urokinase had benefit similar to that of immediate surgery for amputation-free survival but resulted in more hemorrhagic complications.

Source of funding: Abbott Laboratories.

For correspondence: Dr. K. Ouriel, Department of Surgery, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA. FAX 716-756-7750.

Table. Initial thrombolysis vs surgery for arterial leg occlusion*

Outcomes Thrombolysis Surgery RRI (95% CI) NNH (CI)
Death or amputation
At 6 mo 28.2% 25.2% 12% (-15 to 48)† Not significant
At 12 mo 35.0% 30.1% 16% (-9 to 48)† Not significant
Hemorrhagic complications 12.5% 5.5% 128% (26 to 314) 14 (8 to 47)

*Abbreviations defined in Glossary; RRI, NNH, and CI calculated from data in article.
†A correction was made at this point in the table. See correction for details.


The study by Ouriel and colleagues confirms that thrombolysis does not provide a simple panacea for the difficult problem of acute limb ischemia. There are limitations to the findings, some of which are highlighted in the accompanying editorial (1). Outcome measures did not include relevant clinical outcomes, such as residual ischemic symptoms. Therapeutic heparin was omitted from the thrombolysis protocol at the request of the safety monitoring committee after the first 62 cases; subsequent analysis showed this drug to be associated with an increased risk for hemorrhagic complications. The small number of patients recruited per center may suggest limited clinical experience or considerable selection of patients.

Perhaps most important is the heterogeneity of treated patients. Acute arterial occlusion has several causes and various appropriate surgical options. These options range from simple balloon embolectomy to complex vascular reconstruction. Subgroup analysis showed a trend that thrombolysis is less effective than surgery for native vessel occlusion (2) but may be better for recent graft occlusion (3), a finding consistent with subgroup analysis from the Surgery versus Thrombolysis for Ischemia of the Lower Extremity (STILE) study.

This study suggests that for every 14 patients treated by thrombolysis, 3 to 4 will avoid open surgery at the cost of 1 additional hemorrhagic complication. Such a trade-off may be appropriate if the patient is at low risk for thrombolysis and if the required surgery would be complex. Surgeons, radiologists, and patients should jointly consider the relevant risks and benefits of the available options. A multidisciplinary team approach in this emergency situation may have important implications for the organization of vascular services.

Jonathan Michaels, MChir
Northern General Hospital NHS TrustSheffield, England, UK


1. Porter JM. Thrombolysis for acute arterial occlusion of the legs. N Engl J Med. 1998;338:1148-50.

2. Weaver FA, Comerota AJ, Youngblood M, et al. Surgical revascularization versus thrombolysis for nonembolic lower extremity native artery occlusions: results of a prospective randomized trial. The STILE Investigators. Surgery versus Thrombolysis for Ischemia of the Lower Extremity. J Vasc Surg. 1996;24:513-21.

3. Comerota AJ, Weaver FA, Hosking JD, et al. Results of a prospective, randomized trial of surgery versus thrombolysis for occluded lower extremity bypass grafts. Am J Surg. 1996;172:105-12.