Thrombolyse - Thrombolysis

1. Tepe, G., C. Hopfenzitz, et al. (2006). "Peripheral arteries: treatment with antibodies of platelet receptors and reteplase for thrombolysis - APART trial." Radiology 239(3): 892-900
2. Plate, G., I. Jansson, et al. (2006). "Thrombolysis for acute lower limb ischaemia - a prospective, randomised, multicentre study comparing two strategies." Eur J Vasc Endovasc Surg 31(6): 651-60.
3. Dorffler-Melly, J., F. Mahler, et al. (2005). "Adjunctive abciximab improves patency and functional outcome in endovascular treatment of femoropopliteal occlusions: initial experience." Radiology 237(3): 1103-9.
4. Mahler F et al. (2001). "Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: a prospective, randomized multicenter trial." J Endovasc Ther 8(6): 638-47
5. Duda SH et al. (2001). "Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone--a randomized pilot trial (the PROMPT Study). Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis." Radiology 221(3): 689-96
6. Schweizer J et al. (2000). "Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis." Angiology 51(11): 913-23
7. Ouriel K et al. (1998). "A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators." N Engl J Med 338(16): 1105-11
8. Braithwaite BD et al. (1997). "Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group." Br J Surg 84(5): 646-50
9. Weaver FA et al. (1996). "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 24(4): 513-21; discussion 521-3
10. Yusuf SW et al. (1995). "Prospective randomised comparative study of pulse spray and conventional local thrombolysis." Eur J Vasc Endovasc Surg 10(2): 136-41
11. Meyerovitz MF et al. (1995). "Thrombolytic therapy compared with mechanical recanalization in non-acute peripheral arterial occlusions: a randomized trial." J Vasc Interv Radiol 6(5): 775-81
12. Kandarpa K et al. (1993). "Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion." Radiology 188(3): 861-7
13. Cragg AH et al. (1991). "Two urokinase dose regimens in native arterial and graft occlusions: initial results of a prospective, randomized clinical trial." Radiology 178(3): 681-6
14. Berridge DC et al. (1991). "Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis." Br J Surg 78(8): 988-95

1. Tepe, G., C. Hopfenzitz, et al. (2006). "Peripheral arteries: treatment with antibodies of platelet receptors and reteplase for thrombolysis - APART trial." Radiology 239(3): 892-900.
PURPOSE: To prospectively compare the safety and efficacy of combination therapy with the
glycoprotein IIb/IIIa antagonist abciximab plus the third-generation thrombolytic agent reteplase
versus those of therapy with the standard thrombolytic agent urokinase plus abciximab.
MATERIALS AND METHODS: The study was approved by the local ethics committee, and
patient informed consent was obtained. Patients with peripheral arterial occlusions less than 60
days old (n=120) were enrolled in the study: 50 patients (32 men, 18 women; mean age, 67
years; range, 23-88 years) received reteplase plus abciximab and 70 patients (36 men, 34
women; mean age, 68 years; range, 28-88 years) received urokinase plus abciximab. Study end
points were the rate of major complications at 30 days, therapeutic success, and survival without
open surgery or major amputation at follow-up. Fisher exact test was used to compare
treatment groups with respect to dichotomous variables, and the event-free-survival probabilities
were calculated with the Kaplan-Meier method. For the comparison of the lengths of occlusions
among the groups, a two-sample t test was used. RESULTS: Therapeutic success (P=.7) did not
differ between the groups, whereas the time required for thrombolysis was lower in the
urokinase-plus-abciximab group (P=.001). Patients who received reteplase plus abciximab
tended to develop more minor complications (mainly bleeding events) (P<.001). During longterm
follow-up (2-4 years), no group differences were observed. The reocclusion rate was 48%
(22 of 46) in the reteplase-plus-abciximab group and 45% (29 of 64) in the urokinase-plusabciximab
group. Only two of 120 major amputations were counted in the follow-up period.
CONCLUSION: The proposed regimen resulted in only a limited number of major complications,
and the low amputation rate in both groups may be attributed to abciximab.

2. Plate, G., I. Jansson, et al. (2006). "Thrombolysis for acute lower limb ischaemia - a prospective, randomised, multicentre study comparing two strategies." Eur J Vasc Endovasc Surg 31(6): 651-60.
OBJECTIVES: To test if initial high-dose, pulse-spray thrombolysis improves the early and late
outcome of lower limb ischaemia as compared with low-dose infusion alone. DESIGN: Prospective
randomised multicentre study. MATERIAL AND METHODS: Patients with acute and sub-acute
(<30 days) lower limb ischaemia were randomised following angiography. Group 1 (n=58) received
pulse-spray infusion of recombinant plasminogen activator (rt-PA, 15 mg/h) for 2h followed by
low-dose infusion if needed. Group 2 (n=63) were only treated with low-dose infusion (0.5mg/h)
of rt-PA for 48 h. Underlying lesions were corrected if required. RESULTS: The study was stopped
prematurely. Complications were equally frequent in both groups. More than 75% lysis was
accomplished in 78 versus 67% of the patients (p=0.21). Primary endpoints (re-occlusion,
incomplete lysis, life-threatening complication, amputation, or death) were reached in 24 versus
32% of the patients (p=0.35). Neither vascular patency nor clinical parameters differed during the
first year, but re-interventions tended to be more frequent (p=0.040 at 1 month; p=0.090 at 1 year)
and of a greater magnitude (p=0.028) in group 2. CONCLUSIONS: There was no obvious
advantage with initial high-dose thrombolysis, which may be a type-2 error. A reduction of major
re-interventions was recorded.

3.Dorffler-Melly, J., F. Mahler, et al. (2005). "Adjunctive abciximab improves patency and functional outcome in endovascular treatment of femoropopliteal occlusions: initial experience." Radiology 237(3): 1103-9.
PURPOSE: To evaluate the combination of a platelet glycoprotein IIb/IIIa complex receptor inhibitor and urokinase for treatment of recent (<or=6 weeks) arterial occlusion of the legs. MATERIALS AND METHODS: Seventy patients with lower extremity arterial occlusion of less than 6 weeks duration were randomly separated into two treatment groups: urokinase plus abciximab or urokinase plus placebo. Primary end points were the rate of major complications at 30 days after randomization and the rates of amputation-free survival and survival without open surgery or major amputation at follow-up of 90 days. Two readers unaware of the patients' treatment group assignments analyzed digital subtraction angiograms as they related to the study end points, with a final consensus reading. RESULTS: Thrombolysis relative to clot length was faster in the urokinase-plus-abciximab group (odds ratio, 0.52; 95% CI: 0.35, 0.76; P <.001). There were no procedure-related deaths or intracranial hemorrhages, but the rate of nonfatal major bleeding was higher with urokinase plus abciximab (four of 50 patients) than with urokinase alone (none of 20 patients; P =.32). At 90 days, amputation-free survival was 96% (48 of 50 patients) in the urokinase-plus-abciximab group compared with 80% (16 of 20 patients) in the urokinase alone group. The hazard ratio for the two Kaplan-Meier curves was 0.42 (95% CI: 0.16, 0.96; P =.04). CONCLUSION: In patients with lower extremity arterial occlusion who were undergoing urokinase thrombolysis, adjunctive abciximab treatment resulted in faster thrombus dissolution and improved amputation-free survival, despite an increase in major bleeding.

4. Schweizer, J., W. Kirch, et al. (2003). "Use of abciximab and tirofiban in patients with peripheral arterial occlusive disease and arterial thrombosis." Angiology 54(2): 155-61.
Acute peripheral arterial occlusive disease is an important factor affecting the mobility and mortality rate of elderly patients. Catheter-guided arterial thrombolysis in these patients has its limitations: long lysis times, early occlusions, and high restenosis rates. The study investigated whether the use of tirofiban has the same favorable effect as the glycoprotein (GP) IIb/IIIa receptor antagonist abciximab and whether lysis times can be shortened and the disease course positively influenced by these substances. Sixty patients were randomly assigned to 2 groups. Each group received 5 mg recombinant tissue-type (rt-PA) plasminogen activator by slow intra-arterial injection for 10 minutes followed by 5 mg rt-PA per hour and 500 IU heparin per hour IV. After randomization 1 group received a bolus of 0.25 mg abciximab per kg body weight followed by 10 mg per minute IV for 12 hours (heparin was reduced to 250 IU/hr). The other group received a bolus of 0.4 microg tirofiban per kg body weight as well as postinterventional medication with 0.1 microg tirofiban per minute and kg body weight for 24 hours. During medication with GP IIb/IIIa inhibitor, the patients received a reduced heparin dosage for 24 hours. After 24 hours both groups received 200 mg aspirin orally and full heparinization controlled on the basis of the partial thromboplastin time. The following efficacy criteria were analyzed: rehospitalization events, reintervention events, and amputations within 6 months. Secondary endpoints were changes in the Fontaine stage, the crurobrachial index, the distance to claudication, and the duration of local arterial lysis. No significant differences were found between the abciximab and tirofiban groups in terms of the rehospitalization, reintervention, or amputation rates, nor were there any group differences in the total number of events. The secondary parameters, such as the crurobrachial index, distance to claudication, and Fontaine stage, also showed no significant differences between the 2 groups within 6 months. The duration of lysis was significantly shorter in the abciximab group. Major bleeding events did not occur in either group. With regard to the adverse effect rate, there were no significant differences between the 2 groups. Both abciximab and tirofiban can be used successfully in patients with peripheral arterial occlusive disease and arterial thrombosis.

5. Mahler, F., E. Schneider, et al. (2001). "Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: a prospective, randomized multicenter trial." J Endovasc Ther 8(6): 638-47.
PURPOSE: To report the outcome of a prospective, randomized, open multicenter trial comparing (1) the effects of local thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) and (2) 2 administration techniques. METHODS: Two hundred thirty-four patients with thromboembolic occlusions in 223 native femoral or popliteal arteries (95%) and 11 bypass grafts (5%) were randomized to rtPA (n = 124) or UK (n = 110) administered either through an endhole catheter (Hess technique) in 81 patients or a microporous balloon catheter (Schneider technique) in 153 patients. When lysis was incomplete, additional catheter interventions were applied to achieve patency. Results were analyzed by fluoroscopy during intervention and by angiography evaluated by independent experts blinded to the methods applied. RESULTS: The only significant difference between rtPA and UK was found at the end of lysis using the Hess technique. Complete reperfusion (TIMI grade 3) was produced in 60% of patients by rtPA versus 37% by UK (p = 0.045). By both techniques TIMI grade 3 was achieved in 62% with rtPA and in 50% with UK (p = 0.18). Independent of delivery technique, thrombolytic agent, or additional catheter interventions, TIMI grade 3 was achieved in 81% and angiographic patency in 88%. Primary patency at 6 months was 66%, which was increased by secondary interventions to 75%. Major amputations were performed in 6%, all in patients with initial Fontaine stage III/IV ischemia. CONCLUSIONS: With local thrombolysis alone, rtPA appears to be more effective than UK; however, additional catheter interventions further improved patency, abolishing the difference between the lytic agents.

6. Duda, S. H., G. Tepe, et al. (2001). "Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone--a randomized pilot trial (the PROMPT Study). Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis." Radiology 221(3): 689-96.
PURPOSE: To evaluate the combination of a platelet glycoprotein IIb/IIIa complex receptor inhibitor and urokinase for treatment of recent (<or=6 weeks) arterial occlusion of the legs. MATERIALS AND METHODS: Seventy patients with lower extremity arterial occlusion of less than 6 weeks duration were randomly separated into two treatment groups: urokinase plus abciximab or urokinase plus placebo. Primary end points were the rate of major complications at 30 days after randomization and the rates of amputation-free survival and survival without open surgery or major amputation at follow-up of 90 days. Two readers unaware of the patients' treatment group assignments analyzed digital subtraction angiograms as they related to the study end points, with a final consensus reading. RESULTS: Thrombolysis relative to clot length was faster in the urokinase-plus-abciximab group (odds ratio, 0.52; 95% CI: 0.35, 0.76; P <.001). There were no procedure-related deaths or intracranial hemorrhages, but the rate of nonfatal major bleeding was higher with urokinase plus abciximab (four of 50 patients) than with urokinase alone (none of 20 patients; P =.32). At 90 days, amputation-free survival was 96% (48 of 50 patients) in the urokinase-plus-abciximab group compared with 80% (16 of 20 patients) in the urokinase alone group. The hazard ratio for the two Kaplan-Meier curves was 0.42 (95% CI: 0.16, 0.96; P =.04). CONCLUSION: In patients with lower extremity arterial occlusion who were undergoing urokinase thrombolysis, adjunctive abciximab treatment resulted in faster thrombus dissolution and improved amputation-free survival, despite an increase in major bleeding.

7. Schweizer, J., W. Kirch, et al. (2000). "Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis." Angiology 51(11): 913-23.
Acute peripheral occlusive arterial disease is an important cause of morbidity and mortality, particularly among older persons. Catheter-directed thrombolytic therapy is the treatment of choice but has limitations: long lytic times, occlusions refractory to thrombolysis, and a high rate of restenosis. We conducted a pilot study to evaluate the use of the platelet GP IIb/IIIa receptor antagonist abciximab versus aspirin in conjunction with thrombolysis in patients with acute peripheral occlusive arterial disease associated with arterial thrombosis. A total of 84 patients were randomized into two equal groups to receive 5 mg recombinant tissue plasminogen activator intravenously and 500 IU heparin/hour along with either 500 mg acetylsalicylic acid or a bolus of 0.25 mg/kg abciximab followed by 10 microg/min abciximab over 12 hours (heparin reduced to 250 IU/hour). Primary efficacy criteria included the number of rehospitalizations, reinterventions, and amputations during the following 6 months. Secondary endpoints were the changes in the Fontaine stage, Bollinger index (vessel occlusion), ankle-to-brachial ratios, distance to claudication after 6 months, and the duration of the initial local lysis treatment. Adjunctive use of abciximab reduced the rates of rehospitalization, reinterventions, and amputations versus results with the use of aspirin (10 vs 14 occurrences, respectively; 9 vs 11; 3 vs 5; when summed, intergroup difference p < 0.05). Secondary peripheral occlusive arterial disease variables became highly significant versus aspirin (p < 0.001 or greater) at 3 and 6 months after treatment. The duration of lysis was markedly shorter upon addition of abciximab versus aspirin (75 vs 110 min; p < 0.001). No major bleeding complications or embolisms occurred. These preliminary results indicate that abciximab may have a useful role when used adjunctively with a thrombolytic agent in older persons with acute peripheral occlusive arterial disease and arterial thrombosis.

8. Ouriel, K., F. J. Veith, et al. (1998). "A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators." N Engl J Med 338(16): 1105-11.
BACKGROUND: Recent controlled trials suggest that thrombolytic therapy may be an effective initial treatment for acute arterial occlusion of the legs. A major potential benefit of initial thrombolytic therapy is that limb ischemia can be managed with less invasive interventions. METHODS: In this randomized, multicenter trial conducted at 113 North American and European sites, we compared vascular surgery (e.g., thrombectomy or bypass surgery) with thrombolysis by catheter-directed intraarterial recombinant urokinase; all patients (272 per group) had had acute arterial obstruction of the legs for 14 days or less. Infusions were limited to a period of 48 hours (mean [+/-SE], 24.4+/-0.86), after which lesions were corrected by surgery or angioplasty if needed. The primary end point was the amputation-free survival rate at six months. RESULTS: Final angiograms, which were available for 246 patients treated with urokinase, revealed recanalization in 196 (79.7 percent) and complete dissolution of thrombus in 167 (67.9 percent). Both treatment groups had similar significant improvements in mean ankle-brachial blood-pressure index. Amputation-free survival rates in the urokinase group were 71.8 percent at six months and 65.0 percent at one year, as compared with respective rates 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 six months the surgery group had undergone 551 open operative procedures (excluding amputations), as compared with 315 in the thrombolysis group. Major hemorrhage occurred in 32 patients in the urokinase group (12.5 percent) as compared with 14 patients in the surgery group (5.5 percent) (P= 0.005). There were four episodes of intracranial hemorrhage in the urokinase group (1.6 percent), one of which was fatal. By contrast, there were no episodes of intracranial hemorrhage in the surgery group. CONCLUSIONS: Despite its association with a higher frequency of hemorrhagic complications, intraarterial infusion of urokinase reduced the need for open surgical procedures, with no significantly increased risk of amputation or death.

9. Braithwaite, B. D., T. M. Buckenham, et al. (1997). "Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group." Br J Surg 84(5): 646-50.
INTRODUCTION: Accelerated thrombolysis with high-dose bolus tissue plasminogen activator (tPA) may enable patients with more severe acute leg ischaemia to be treated without recourse to surgery. This study was a randomized comparison of two thrombolytic regimens. METHODS: One hundred patients with acute leg ischaemia of less than 30 days' duration were randomized to receive either high-dose bolus tPA (three doses of 5 mg over 30 min, then 3.5 mg/h for up to 4 h, then 0.5-1.0 mg/h) or conventional low-dose tPA (0.5-1.0 mg/h). The groups were well matched for age, cardiovascular risk factors, duration and severity of ischaemia, site, cause and length of arterial occlusion. RESULTS: The median duration of infusion in the high-dose group was 4.0 (range 0.25-46) h compared with 20 (range 2-46) h for low-dose infusion (P < 0.0001). Successful thrombolysis was achieved in 45 of 49 high-dose and 39 of 44 low-dose infusions but significantly more adjunctive procedures were required following high-dose bolus infusion (26 versus 16 patients) (P = 0.002). Thirty days after treatment was commenced, limb salvage was achieved in 39 of 49 patients in the high-dose group compared with 37 of 44 who had a low-dose infusion of tPA. Six and two patients respectively required amputation. Four patients in the high-dose group and five in the low-dose group died. Three patients in each group suffered a major haemorrhage and one in the low-dose group had a stroke. CONCLUSION: High-dose bolus therapy significantly accelerated thrombolysis with tPA without compromising outcome. Some 50 per cent of patients were treated within 4 h enabling thrombolysis to be used as primary therapy for patients with acute critical ischaemia.

10. Weaver, F. A., A. J. Comerota, et al. (1996). "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 24(4): 513-21; discussion 521-3.
PURPOSE: Early results of a prospective study that compared surgical revascularization and thrombolysis for lower extremity arterial and graft occlusions have been published. This report details the final results in patients who have native artery occlusions. METHODS: Two hundred thirty-seven patients who had lower extremity ischemia as a result of iliac-common femoral (IF; 69 patients) or superficial femoral-popliteal (FP; 168 patients) occlusion, and had symptomatically deteriorated within the past 6 months were randomized to catheter-directed thrombolysis (150 patients) or surgical revascularization (87 patients). After diagnostic arteriographic examination but before randomization, the optimal surgical procedure was determined. Lytic patients were randomized to recombinant tissue plasminogen activator (rt-PA; 84 patients) or urokinase (UK; 66 patients). Recurrent ischemia, morbidity, amputation, and death rates were determined at 30 days, 6 months, and 1 year, and were analyzed on an intent-to-treat basis. RESULTS: For patients randomized to lysis, a catheter was properly positioned and the lytic agent delivered in 78%. This provided a reduction in the predetermined surgical procedure in 58% of patients who had an FP occlusion and 51% of those who had an IF occlusion. rt-PA and UK were equally effective and safe, but lysis time was shorter with rt-PA (8 vs 24 hr; p < 0.05). At 1 year, the incidence of recurrent ischemia (64% vs 35%; p < 0.0001) and major amputation (10% vs 0%; p = 0.0024) was increased in patients who were randomized to lysis. Factors associated with a poor lytic outcome included FP occlusion, diabetes, and critical ischemia. No differences in mortality rates were observed at 1 year between the lysis and surgical groups. CONCLUSION: Surgical revascularization for lower extremity native artery occlusions is more effective and durable than thrombolysis. Thrombolysis used initially provides a reduction in the surgical procedure for a majority of patients; however, long-term outcome is inferior, particularly for patients who have an FP occlusion, diabetes, or critical ischemia.

11. Yusuf, S. W., S. C. Whitaker, et al. (1995). "Prospective randomised comparative study of pulse spray and conventional local thrombolysis." Eur J Vasc Endovasc Surg 10(2): 136-41.
OBJECTIVES: To compare the time required to achieve lysis with the pulse spray technique and the conventional slow continuous infusion technique. DESIGN: Prospective randomised open Study. METHODS: Eighteen patients suitable for intra-arterial thrombolytic therapy with conventional and pulse spray technique were randomised 1:1 to receive either pulse spray thrombolysis with 0.33 mg/ml rt-PA injected as a bolus of 0.2 ml or conventional thrombolysis with 0.05 mg/ml rt-PA infused at a rate of 10 ml/h. RESULTS: The age, duration of symptoms, length of occlusion and prethrombolysis ankle brachial pressure index were comparable in the two groups. The median duration of thrombolytic therapy in the pulse spray group was 195 min (range 90-1260) compared to 1390 min (range 300-2400) in the Conventional group. The difference between the two groups was significant, p < 0.002 (Mann-Whitney test). CONCLUSIONS: Significantly shorter time is required to achieve local thrombolysis with pulse spray compared to the conventional infusion method.

12. Meyerovitz, M. F., D. Didier, et al. (1995). "Thrombolytic therapy compared with mechanical recanalization in non-acute peripheral arterial occlusions: a randomized trial." J Vasc Interv Radiol 6(5): 775-81.
PURPOSE: To evaluate whether thrombolytic therapy followed by angioplasty has any added benefit compared with angioplasty alone for the treatment of chronic peripheral arterial occlusions. PATIENTS AND METHODS: Twenty patients with claudication or limb-threatening ischemia of at least 3 weeks duration due to iliac or femoropopliteal artery occlusions were randomized either to thrombolytic therapy with recombinant tissue-type plasminogen activator for up to 4 hours (n = 11) followed by angioplasty or to angioplasty alone (n = 9). Clinical follow-up was obtained for 1 year. RESULTS: Life-table analysis revealed a significant improvement in the cumulative primary patency rate for patients with claudication treated initially with thrombolysis followed by angioplasty (n = 7; 86% at 6 months; 51% at 1 year) compared with angioplasty alone (n = 9; 11% at 6 months and 1 year) (P <.02). All four patients with limb-threatening ischemia were randomized to thrombolytic therapy, and none exhibited continued patency at 1 year. The most common complication in the thrombolysis group was peripheral embolization; three of these four patients were among those who had limb-threatening ischemia as the indication for entry into this study. There was no increased incidence of bleeding with thrombolytic therapy. CONCLUSIONS: A short course of thrombolytic therapy prior to angioplasty appears to improve the 1-year patency rate for claudication due to iliac or femoropopliteal occlusions. However, patients with limb-threatening ischemia have a high prevalence of peripheral embolization and dismal patency rates with this form of therapy. A larger scale study is necessary to confirm these findings.

13. Kandarpa, K., P. S. Chopra, et al. (1993). "Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion." Radiology 188(3): 861-7.
A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P =.01).

14. Cragg, A. H., T. P. Smith, et al. (1991). "Two urokinase dose regimens in native arterial and graft occlusions: initial results of a prospective, randomized clinical trial." Radiology 178(3): 681-6.
The effects of two urokinase (UK) dose regimens on lysis time, lytic success, primary clinical success, and frequency of complications of peripheral thrombolysis were compared. Seventy-two intraarterial UK infusions were performed by means of standard catheter-directed infusion techniques in 63 patients with symptomatic peripheral arterial or bypass graft occlusions. Patients were prospectively randomized to high-dose (250,000 U/h for 4 hours and then 125,000 U/h) or low-dose (50,000 U/h) regimens. The mean time to complete lysis was 20.8, 26.0, 16.5, and 18.2 hours for the high-dose artery, low-dose artery, high-dose graft, and low-dose graft groups, respectively (P was not significant). Respective mean infusion durations were 27.1, 35.4, 22.2, and 25.3 hours. Clinical success was achieved in 65%-85% of cases. The frequency of complications was equivalent between groups, except for a higher frequency of minor bleeding complications in the high-dose group. The two urokinase dose regimens studied were equally effective in enabling peripheral thrombolysis

15. Berridge, D. C., R. H. Gregson, et al. (1991). "Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis." Br J Surg 78(8): 988-95.
Sixty patients were recruited into a randomized parallel group comparison of three thrombolytic regimens for acute or subacute peripheral arterial thrombosis. There were no significant differences in age, duration of history, length of occlusion or presence of neurosensory deficit between the groups. Initially successful lysis was significantly greater with intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) than with either streptokinase (Sk) (P less than 0.04) or intravenous (IV) rt-PA (P less than 0.01). The duration of therapy varied from a median of 35 h with IA rt-PA to 40 h with Sk (P greater than 0.5). The median (confidence interval) increase in ankle:brachial pressure index following IA rt-PA of 0.57 (0.33-0.82) was significantly higher than for either Sk of 0.24 (0-0.57) or for IV rt-PA of 0.18 (0-0.41). Limb salvage at 30 days was achieved in 80, 60 and 45 per cent respectively for IA rt-PA, Sk and IV rt-PA. Haemorrhagic complications occurred in six patients following Sk and in 13 following IV rt-PA; only one minor haemorrhage occurred following a catheter perforation in a patient who received IA rt-PA (P less than 0.05). IA rt-PA provides a more effective, safer fibrinolytic regimen than conventional therapy with Sk. IV rt-PA has not been as successful and carries a significantly higher risk of haemorrhagic complications.