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Clopidogrel is more effective than aspirin as adjuvant treatment to prevent reocclusion after thrombolysis
S K Yao1, J C Ober, J J Ferguson
1Cardiovascular Research Laboratory, Texas Heart Institute/St. Luke's Episcopal Hospital, Houston.
Insights
Clopidogrel, an ADP inhibitor, reduced reocclusion after thrombolysis with tissue-type plasminogen activator (t-PA) better than aspirin. Higher doses of clopidogrel were most effective in preventing reocclusion in a canine model.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Thrombosis Research
Background:
- Platelet aggregation is crucial in thrombosis.
- Thienopyridine derivatives like clopidogrel inhibit adenosine diphosphate (ADP)-induced platelet aggregation.
- Tissue-type plasminogen activator (t-PA) is used for thrombolysis, but reocclusion is a concern.
Purpose of the Study:
- To compare the efficacy of clopidogrel versus aspirin as adjunctive treatments to t-PA for thrombolysis and prevention of reocclusion.
- To evaluate the dose-dependent effect of clopidogrel in preventing reocclusion.
Main Methods:
- A canine model of coronary artery thrombosis was established.
- Animals received intravenous t-PA and heparin, with or without aspirin or clopidogrel.
- Coronary blood flow velocity was monitored using a Doppler flow probe.
- Thrombolysis time and reocclusion rates were assessed.
Main Results:
- Thrombolysis times were similar across groups, with no significant difference compared to t-PA and heparin alone.
- Reocclusion rates were significantly lower in dogs treated with clopidogrel compared to aspirin or control (P < 0.001).
- The higher dose of clopidogrel (10 mg/kg + 2.5 mg/kg/h) completely prevented reocclusion in all treated animals.
Conclusions:
- Clopidogrel is more effective than aspirin in preventing reocclusion after t-PA-induced thrombolysis.
- Higher doses of clopidogrel demonstrate superior efficacy in maintaining vessel patency.
- Clopidogrel shows promise as an adjunctive therapy to improve outcomes in acute thrombotic events.
Abstract:
Clopidogrel is a thienopyridine derivative and a potent inhibitor of ADP-induced platelet aggregation. We compared clopidogrel with aspirin as an adjunctive treatment to tissue-type plasminogen activator (t-PA) for thrombolysis and reocclusion. Thrombosis was induced in coronary arteries of 32 dogs by injuring the endothelium with an electric charge. Coronary blood flow velocity was monitored by a pulsed Doppler flow probe placed around the artery. After the artery had been occluded by a thrombus for 3 continuous hours, each animal was given one of the following intravenous treatments: 1) t-PA (80 micrograms/kg + 8 micrograms.kg-1.h-1) and heparin (200 U/kg) (group 1, n = 7); 2) t-PA, heparin, and aspirin (5 mg/kg) (group 2, n = 8); 3) t-PA, heparin, and clopidogrel (5 mg/kg) (group 3, n = 9); and 4) t-PA, heparin, and clopidogrel (10 mg/kg + 2.5 mg.kg-1.h-1) (group 4, n = 8). After treatment, thrombolysis developed in 45 +/- 12 min in group 1, 39 +/- 10 min in group 2, 39 +/- 10 min in group 3, and 27 +/- 10 min in group 4 (compared with group 1, P > 0.05). After thrombolysis, reocclusion occurred in 5 of 5 dogs in group 1 and 7 of 7 in group 2, but only 2 of 7 in group 3 and none of 7 in group 4 (compared with groups 1 and 2, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)