Reteplase monotherapy and reteplase/abciximab combination therapy in peripheral arterial occlusive disease: results from the RELAX trial.
OBJECTIVE
The safety and efficacy of increasing doses of intraarterial reteplase monotherapy and reteplase/abciximab combination therapy were examined in patients with acute peripheral arterial occlusive disease (PAOD). The primary endpoint of this analysis was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) investigators.


METHODS
The RELAX trial was a prospective, dose-escalating safety trial of reteplase monotherapy (0.1, 0.2, 0.5, or 1.0 U/h) and reteplase/abciximab combination therapy (0.25-mg/kg bolus and 0.125 micro g/kg/min abciximab in addition to each reteplase regimen) for patients with acute or subacute clinical deterioration of PAOD. Reteplase was administered intraarterially to 74 patients; 38 patients were also administered intravenous abciximab for the duration of reteplase infusion. Protocol-specified angiograms were obtained at 6 and 20 hours or for clinical need. Each angiogram was assessed for volume of thrombus dissolved and for arterial patency. The primary safety endpoint (TIMI major bleeding) was assessed at discharge and at day 7. Clinical endpoints were assessed at discharge and at days 30 and 90.


RESULTS
Major bleeding occurred with similar frequency in patients treated with and without abciximab (15% of the pooled patients receiving reteplase monotherapy and 20% of patients receiving reteplase/abciximab combination therapy). There were no intracranial hemorrhagic events in the 74 patients. Reteplase doses of at least 0.2 U/hour were effective at dissolving thrombus and restoring patency. There was no clear dose-response relationship for reteplase. However, the addition of abciximab reduced the occurrence of distal embolic events requiring intervention (5% vs. 31%; P =.014).


CONCLUSIONS
Over the range of reteplase doses studied for peripheral arterial thrombolysis, there were no significant differences in safety or efficacy. However, the addition of intravenous abciximab to reteplase was associated with a decreased rate of distal embolic events without a significant increase in the risk of hemorrhagic complications. Further investigation is needed to define the role of abciximab in catheter-directed thrombolysis with reteplase for PAOD.
Ouriel
Kenneth
K
Department of Vascular Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. ourielk@ccf.org
Castaneda
Flavio
F
McNamara
Thomas
T
Swischuk
James
J
Tepe
Gunnar
G
Smith
John J
JJ
Clark
Jason
J
Duda
Stephan
S
D000077284:Abciximab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006083:Graft Occlusion, Vascular / Q000188:drug therapy; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D012449:Safety; D013927:Thrombosis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator; D000077284:Abciximab