Background Recent controlled trials suggest that thrombolytictherapy may be an effective initial treatment for acute arterialocclusion of the legs. A major potential benefit of initialthrombolytic therapy is that limb ischemia can be managed withless invasive interventions.
Methods In this randomized, multicenter trial conducted at 113North American and European sites, we compared vascular surgery(e.g., thrombectomy or bypass surgery) with thrombolysis bycatheter-directed intraarterial recombinant urokinase; all patients(272 per group) had had acute arterial obstruction of the legsfor 14 days or less. Infusions were limited to a period of 48hours (mean [±SE], 24.4±0.86), after which lesionswere corrected by surgery or angioplasty if needed. The primaryend point was the amputation-free survival rate at six months.
Results Final angiograms, which were available for 246 patientstreated with urokinase, revealed recanalization in 196 (79.7percent) and complete dissolution of thrombus in 167 (67.9 percent).Both treatment groups had similar significant improvements inmean ankle–brachial blood-pressure index. Amputation-freesurvival rates in the urokinase group were 71.8 percent at sixmonths and 65.0 percent at one year, as compared with respectiverates of 74.8 percent and 69.9 percent in the surgery group;the 95 percent confidence intervals for the differences were-10.5 to 4.5 percentage points at six months (P = 0.43) and-12.9 to 3.1 percentage points at one year (P = 0.23). At sixmonths the surgery group had undergone 551 open operative procedures(excluding amputations), as compared with 315 in the thrombolysisgroup. Major hemorrhage occurred in 32 patients in the urokinasegroup (12.5 percent) as compared with 14 patients in the surgerygroup (5.5 percent) (P = 0.005). There were four episodes ofintracranial hemorrhage in the urokinase group (1.6 percent),one of which was fatal. By contrast, there were no episodesof intracranial hemorrhage in the surgery group.
Conclusions Despite its association with a higher frequencyof hemorrhagic complications, intraarterial infusion of urokinasereduced the need for open surgical procedures, with no significantlyincreased risk of amputation or death.
Source Information
From the Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, N.Y. (K.O.); the Department of Surgery, Albert Einstein School of Medicine, Bronx, N.Y. (F.J.V.); and the Department of Medicine, Harvard Medical School, Boston (A.A.S.).
Address reprint requests to Dr. Ouriel at the Department of Surgery, University of Rochester, 601 Elmwood Ave., Rochester, NY 14642.
Gray, B. H., Conte, M. S., Dake, M. D., Jaff, M. R., Kandarpa, K., Ramee, S. R., Rundback, J., Waksman, R., for Writing Group 7,
(2008). Atherosclerotic Peripheral Vascular Disease Symposium II: Lower-Extremity Revascularization: State of the Art. Circulation
118: 2864-2872
[Full Text]
Dick, F., Li, J., Giraud, M.-N., Kalka, C., Schmidli, J., Tevaearai, H.
(2008). Basic Control of Reperfusion Effectively Protects Against Reperfusion Injury in a Realistic Rodent Model of Acute Limb Ischemia. Circulation
118: 1920-1928
[Abstract][Full Text]
Olvey, E. L., Skrepnek, G. H., Nolan, P. E. Jr.
(2008). Cost-effectiveness of urokinase and alteplase for treatment of acute peripheral artery disease: Comparison in a decision analysis model. Am J Health Syst Pharm
65: 1435-1442
[Abstract][Full Text]
Sobel, M., Verhaeghe, R.
(2008). Antithrombotic Therapy for Peripheral Artery Occlusive Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 815S-843S
[Abstract][Full Text]
Amonkar, S.J., Cleanthis, M., Nice, C., Timmons, G., Mudawi, A.M., Ashour, H.Y., Bhattacharya, V.
(2008). Outcomes of Intra-arterial Thrombolysis for Acute Limb Ischemia. ANGIOLOGY
58: 734-742
[Abstract]
Shrivastava, C. P, Devgarha, S.
(2007). Urokinase Thrombolysis in Acute-on-Chronic Vascular Occlusion of Lower Limb. Asian Cardiovasc. Thorac. Ann.
15: 405-407
[Abstract][Full Text]
Tepe, G., Hopfenzitz, C., Dietz, K., Wiskirchen, J., Heller, S., Ouriel, K., Ziemer, G., Claussen, C. D., Duda, S. H.
(2006). Peripheral Arteries: Treatment with Antibodies of Platelet Receptors and Reteplase for Thrombolysis--APART Trial. Radiology
239: 892-900
[Abstract][Full Text]
Slovut, D. P, Bacharach, J M.
(2005). Endovascular treatment of an occluded axillofemoral bypass graft. Vasc Med
10: 33-36
[Abstract]
Clagett, G. P., Sobel, M., Jackson, M. R., Lip, G. Y. H., Tangelder, M., Verhaeghe, R.
(2004). Antithrombotic Therapy in Peripheral Arterial Occlusive Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 609S-626S
[Abstract][Full Text]
Wright, L. B., Matchett, W. J., Cruz, C. P., James, C. A., Culp, W. C., Eidt, J. F., McCowan, T. C.
(2004). Popliteal Artery Disease: Diagnosis and Treatment. RadioGraphics
24: 467-479
[Abstract][Full Text]
Drescher, P., McGuckin, J., Rilling, W. S., Crain, M. R.
(2003). Catheter-Directed Thrombolytic Therapy in Peripheral Artery Occlusions: Combining Reteplase and Abciximab. Am. J. Roentgenol.
180: 1385-1391
[Abstract][Full Text]
Stewart, D., Kong, M., Novokhatny, V., Jesmok, G., Marder, V. J.
(2003). Distinct dose-dependent effects of plasmin and TPA on coagulation and hemorrhage. Blood
101: 3002-3007
[Abstract][Full Text]
Alving, B. M., Francis, C. W., Hiatt, W. R., Jackson, M. R.
(2003). Consultations on Patients with Venous or Arterial Diseases. ASH Education Book
2003: 540-558
[Abstract][Full Text]
Stonebraker, J. S.
(2002). How Bayer Makes Decisions to Develop New Drugs. Interfaces
32: 77-90
[Abstract]
Baker, W. F. Jr
(2002). Thrombolytic Therapy. CLIN APPL THROMB HEMOST
8: 291-314
Wittich, G. R., Engelke, C., Morgan, R. A., Belli, A.-M.
(2001). Invited Commentary Authors' Response. RadioGraphics
21: 1248-1250
[Full Text]
Makin, A. J., Conway, D. S. G., Lip, G. Y. H., Frost, L., Johnsen, S. P., Engholm, G., Henneberg, E., Husted, S.
(2001). Systemic Thromboembolism in Atrial Fibrillation. Arch Intern Med
161: 1920-1924
[Full Text]
Jain, D., Kurz, T., Katus, H. A., Richardt, G.
(2001). A Unique Complication During Coronary Angiography: Peripheral Embolism by Selective Right Coronary Engagement: A Case Report. ANGIOLOGY
52: 493-499
[Abstract]
Jackson, M. R., Clagett, G. P.
(2001). Antithrombotic Therapy in Peripheral Arterial Occlusive Disease. Chest
119
: 283S-299S
[Full Text]
Zarins, C. K., Gurewich, V., Ouriel, K., Porter, J. M.
(1998). A Comparison of Recombinant Urokinase with Vascular Surgery for Acute Arterial Occlusion of the Legs. NEJM
339: 564-565
[Full Text]
(1998). Thrombolysis vs. Surgery for Acute Arterial Occlusion of the Legs. JWatch General
1998: 5-5
[Full Text]
Porter, J. M.
(1998). Thrombolysis for Acute Arterial Occlusion of the Legs. NEJM
338: 1148-1150
[Full Text]
Duda, S. H., Tepe, G., Luz, O., Ouriel, K., Dietz, K., Hahn, U., Pereira, P., Marsalek, P., Ziemer, G., Erley, C. M., Claussen, C. D.
(2001). Peripheral Artery Occlusion: Treatment with Abciximab plus Urokinase versus with Urokinase Alone— A Randomized Pilot Trial (the PROMPT Study). Radiology
221: 689-696
[Abstract][Full Text]
Previous
