Current Options in the Diagnosis and Management of Acute Limb Ischemia

Karthikeshwar Kasirajan, MD, Kenneth Ouriel, MD

Disclosures

Prog Cardiovasc Nurs. 2002;17(1) 

In This Article

Studies of Thrombolysis vs. Primary Operation

Thrombolysis with such agents as urokinase, rt-PA, streptokinase (Streptase, Astra Pharmaceutical, Eatontown, NJ), and reteplase has been investigated in uncontrolled trials as a therapeutic alternative to operation for acute peripheral arterial occlusion. In the 1990s, three multicenter, randomized trials were published in which thrombolysis was compared with operation for arterial occlusion. The first trial, the Rochester study,[10] randomly assigned 114 patients with acute, limb-threatening ischemia to thrombolysis with urokinase in 57 patients or to immediate operation in 57 patients. At 1 year, the amputation-free survival rates were 75% and 52%, respectively, a statistically significant difference. A closer analysis revealed this finding to be the result of a higher rate of death in the operative group -- deaths that occurred in association with perioperative cardiopulmonary complications. It appeared that the need to take patients with very severe ischemia directly to surgery, without the opportunity for preparation, resulted in a high frequency of complications that culminated in patient demise.

The second large, multicenter evaluation was the Surgery vs. Thrombolysis for Ischemia of the Lower Extremity (STILE) trial.[2] In this study, 393 patients were randomly assigned to surgery or thrombolysis with either rt-PA or urokinase. Clinical outcomes for both thrombolytic groups were similar, so their data were combined for an overall comparison of thrombolysis with surgery. Post hoc stratification of patients into two subgroups on the basis of the duration of symptoms before enrollment (>14 days vs. <14 days) showed that among patients with symptoms of longer duration, the surgical group had lower amputation rates than the thrombolysis group at 6 months (3% vs. 12%). In contrast, among patients with symptoms of shorter duration, those assigned to thrombolysis had lower rates than did surgical patients (11% vs. 30%).

The third multicenter trial to evaluate thrombolytic therapy was the Thrombolysis or Peripheral Arterial Surgery (TOPAS) trial.[11] Recombinant urokinase (r-UK) (4000 IU per minute for 4 hours followed by 2000 IU per minute) was compared to primary operation in 544 patients with lower extremity native artery or bypass graft occlusions of 14 days' duration or less. The amputation-free survival rates 6 months after randomization were not significantly different: 71.8% in the r-UK and 74.8% in the operative group. There were also no significant differences in the rates of amputation-free survival or mortality at discharge from the hospital. At the end of 6 months, 31.5% of the patients in the r-UK group had avoided amputation or death without the need for more than percutaneous procedures. By contrast, the vast majority of the patients randomized to primary operation underwent open surgery -- 94.2%, a rate that was not unexpected due to the design of the trial. The median length of hospitalization was 10 days in both treatment groups. Among patients assigned to thrombolysis, those with occlusions in bypass grafts had better clinical outcomes and rates of clot dissolution, concurrent with lower rates of major hemorrhagic complications, compared to patients with native artery occlusions.

Major hemorrhage complications occurred in 32 patients (12.5%) in the r-UK group, as compared with 14 patients (5.5%) in the surgery group among the TOPAS trial patients. Patients' ages, duration of infusion, and activated partial thromboplastin times at baseline were unrelated to the risk of bleeding. Intracranial hemorrhage occurred in four patients in the r-UK group (1.6%), one of whom died. By contrast, there were no instances of intracranial hemorrhage in the surgery group. The risk of bleeding was significantly greater when therapeutic heparin was utilized than when it was not. Among 102 patients who received therapeutic heparin, bleeding occurred in 19 (19%). By contrast, in the 150 patients in whom therapeutic heparin was not utilized, bleeding occurred in only 13 patients (9%). A comparison of the results of the three large trials comparing open surgery with thrombolysis is given in Table 4 .

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