Can read freely here https://sethiortho.blogspot.com/ A COMPARISON OF RECOMBINANT UROKINASE WITH VASCULAR SURGERY AS INITIAL TREATMENT FOR ACUTE ARTERIAL OCCLUSION OF THE LEGS For the thrombolysis or peripheral arterial surgery (TOPAS) investigators RCT The Rochester study -1994 Surgery Vs Thrombolysis for Ischemia of the Lower Extremity (STILE) - 1996 endovascular surgery

1. A COMPARISON OF RECOMBINANT UROKINASE WITH
VASCULAR SURGERYAS INITIAL TREATMENT FOR ACUTE ARTERIAL OCCLUSION OF THE
LEGS
For the thrombolysis or peripheral arterial surgery (TOPAS) investigators
RCT, Conducted at North American and European Hospitals
Published in New England Journal of Medicine - April 1998
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SethiNet Presentations

2. Background…….
• ALI – Primary goal of management is restoration of arterial flow
1. Surgical revascularization
2. Pharmacologic dissolution of thrombus.
• Surgical intervention is associated with a substantial risk of limb loss and
death
• Later thrombolysis with minimal surgical intervention technique was
introduced
• Popular trials showed thrombolysis with minimal surgical intervention can
minimize the complications and increase in patient survival rates.

3. Background - The Rochester study -1994
• Study was done on 114 patients with ALI
• 57 patients underwent thrombolysis with urokinase +/- surgery
• 57 patients underwent immediate operation
Results
One year amputation-free survival rates
• 75% - urokinase therapy
• 52% - surgery
Conclusions
Intraarterial thrombolytic therapy was associated with a reduction in the incidence of complications
and a corresponding increase in patient survival rates.
Thrombolytic therapy may offer a safe and effective alternative to operation in the initial
treatment.

4. 150 pts underwent catheter directed thrombolysis
87 pts underwent surgical revascularization.
Conclusions….
1. A significant reduction in planned surgical procedure is observed after
thrombolysis
2. Ongoing/recurrent ischemia is greater in the patients undergoing thrombolysis
3. Patients with acute ischemia (<14 days) who were treated with
thrombolysis had improved amputation-free survival and shorter hospital
stays.
Surgery Vs Thrombolysis for Ischemia of the Lower Extremity (STILE) - 1996

5. Objective of this study
• Compare the efficacy (as assessed by amputation free survival) and safety of
catheter-administered urokinase therapy and conventional open surgery as
initial treatment in patients with acute limb ischemia of the leg.

6. TOPAS trial - Methods
• Total 572 patients (Each group contain 272 patients)
• Inclusion criteria
• Acute lower-limb ischemia < 14 - days duration
• Occlusion confirmed with arteriography
• Age > 17 yrs old
• Eligible for both operative and thrombolytic intervention
• Exclusion criteria
• Risk of bleeding

7. Methods…
Urokinase was infused through an intraarterial catheter at a rate of 4000 IU/m during initial
4hr & then at a rate of 2000 IU/m
Concurrent unfractionated heparin was also administered intravenously to reach a target
APTT (1.5 – 2)
Infusions were stopped
• when lysis was complete
• when no further progress was evident on arteriography
• After 48 hours of therapy
After which lesions were corrected by surgery or angioplasty if needed

8. Outcome measurement
The primary end point
• Amputation-free survival rate at six months after treatment.
Secondary end points
• Survival free of open surgical procedures at six months
• Amputation-free survival at one year
• The degree of clot lysis
• Ankle–brachial blood-pressure index
• The rates of adverse effects of treatment.

9. Results
Thrombolytic group Number Percentage
Recanalization 196 79.7%
Complete dissolution of thrombus 167 67.9%

10. Results….
Thrombolytic Surgery
Length of hospitalization
No significant difference
Ankle –Brachial BP index

11. Amputation free survival rates
Amputation-free survival
rates
6months 1 year
Thrombolytic 71.8% 65%
Surgery 74.8% 69.9%
P value 0.43 0.23

12. Mortality rates
Mortality At Discharge At One year
Thrombolytic 8.8% 12.3%
Surgery 5.3% 17.0%
P value 0.19 0.22

13. Operative interventions
Thrombolyt – No of interventions Surgery - No of interventions
6months 1 year 6months 1year
Amputation 48 58 41 51
Open surgery 315 351 551 590
Percutaneous procedure 128 135 55 70

14. Haemorrhagic Complications
Thrrobolytic group Surgery group P value
12.5% 5.5% P 0.005
Intracranial hemorrhage occurred in four patients in the urokinase group,
one of whom died on the second day of hospitalization.
There was a significant association between the coadministration of
heparin and the risk of major bleeding (P =0.02)

15. Results…
In this study, initial thrombolytic therapy was not superior to operative intervention
with respect to the major end points of survival and limb salvage. Indeed, there was
a trend toward a higher amputation-free survival rate in the surgical group.
In this study data suggest that the risk of hemorrhage can be reduced by restricting
the concomitant use of heparin.

16. Conclusion
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.

17. Thank you