Combination Reperfusion Therapy in Acute MI
abstract & commentary
Source: SPEED group: Trial of abciximab with and without low-dose reteplase for acute myocardial infarction.
Circulation 2000;101:2788-2794.
Recent studies suggest that fibrinolysis and platelet aggregation inhibition may play complementary roles in the treatment of acute myocardial infarction (AMI). In this GUSTO IV (Global Use of Strategies To Open occluded coronary arteries) pilot study, the SPEED (Strategies for Patency Enhancement in the ED) investigators studied the glycoprotein (GP) IIb/IIIa inhibitor abciximab in combination with the fibrinolytic agent reteplase for the treatment of AMI. In phase A, 304 AMI patients (presenting within 12 hours of symptom onset) were randomized to abciximab alone or with varying doses of reteplase. Subsequently, in phase B, the best regimen from phase A was compared with standard reteplase (two 10 unit boluses 30 minutes apart). Patients received aspirin and either standard (60 mcg/kg) or low-dose (40 mcg/kg) heparin. Angiography was performed within 60-90 minutes of therapy initiation to assess TIMI 3 flow (complete reperfusion). Other end points included death, reinfarction, urgent revascularization, stroke, and bleeding. Abciximab with half-dose reteplase (two 5 unit boluses) and standard heparin had the highest efficacy, with more than 61% of patients having TIMI-3 flow (compared to 27% with abciximab only in phase A, and 47% with standard reteplase only in phase B). There was a trend in composite end point (death/reinfarction/revascularization) favoring this combination therapy vs. standard reteplase (11.0 vs 6.1%, P = 0.19). Combination therapy was associated with a trend toward increased bleeding, but there was no difference in intracranial hemorrhage or need for transfusion. The investigators conclude that adding abciximab to half-dose reteplase in the treatment of AMI safely enhances early complete reperfusion.
COMMENT BY ThEoDore C. CHAN, MD, FACEP
From a pathophysiology standpoint, therapies aimed at treating both the fibrin clot and platelet aggregation that occur with coronary plaque rupture and thrombosis make sense. The SPEED study adds to a growing body of literature, including the recently published TIMI-14 trial,1 suggesting that the combination of a GP IIB/IIIA inhibitor with a fibrinolytic agent is safe and effective as a strategy for reperfusion after AMI. The investigators reported that half-dose reteplase with abciximab was most effective, suggesting that combination therapy may allow for a decrease in dosing, and possibly in associated complications. Moreover, in addition to the recent PACT trial,2 this study suggests that pharmacologic and immediate mechanical reperfusion therapy is compatible—contrary to previous beliefs. The overall rate of interventional procedural success was 87%, with no difference among the treatment groups. It should be noted that this study was industry-sponsored and did not compare the combination of other GP IIb/IIIa inhibitors or fibrinolytic agents currently available. In addition, as a pilot study, the overall number of subjects (528) was relatively small, and the study lacked sufficient power to adequately assess the complication rates and clinical end points. However, SPEED has now established the basis for the ongoing GUSTO-IV study, which will enroll more than 16,000 patients for comparison of abciximab with half-dose reteplase vs. standard reteplase therapy in AMI.
References
- Antman EM, et al. Abciximab facilitates the rate and extent of thrombolysis: Results of the thrombolysis in myocardial infarction (TIMI) 14 trial. Circulation 1999;99:2720-2732.
- Ross AM, et al. A randomized trial comparing primary angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: The PACT trial. J Am Coll Cardiol 1999;34:1954-1962.
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