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Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation acute myocardial infarction: a substudy of the randomized double blind CLARITY-TIMI 28 trial

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Abstract

Background

Fibrinolytic therapy for acute ST-elevation myocardial infarction (STEMI) is frequently limited by delays in administration and by incomplete reperfusion or reocclusion of the infarct-related artery. Intensified prehospital management of STEMI may shorten time to treatment and improve outcomes.

Methods

We carried out a prospective substudy in 11 ambulance systems in 216 of the 3,491 patients with STEMI who were enrolled in the CLARITY-TIMI 28 trial. They were randomized in the ambulance to clopidogrel (n = 109) or placebo (n = 107) along with fibrinolysis, aspirin, and heparin. The primary endpoint was the composite of an occluded infarct-related artery (TIMI flow grade 0 or 1), or death or recurrent myocardial infarction before angiography.

Results

All patients received a fibrin-specific lytic and the baseline characteristics in both groups were comparable. The incidence of the primary endpoint was 16.5% in the clopidogrel-treated and 27.1% in the placebo patients (adj OR 0.62, 95% CI 0.31–1.21, p = 0.16), an effect that was consistent with the effects seen in the in-hospital patients in the main CLARITY-TIMI 28 trial. Prehospital clopidogrel therapy reduced the incidence of an occluded infarct-related artery on the predischarge angiogram (11.8% vs. 22.3%, adj OR 0.52, 95% CI 0.24–1.13, p = 0.10). The 30-day incidence of cardiovascular death, recurrent MI or recurrent myocardial ischemia requiring urgent revascularization was 12.8% vs. 14.0% (adj OR 1.07, 95% CI 0.48–2.39, p = 0.87). Early TIMI major bleeding occurred in no clopidogrel patients compared with two placebo patients (1.9%).

Conclusions

Addition of clopidogrel to medical reperfusion of STEMI with fibrinolysis, heparin, and aspirin before reaching the hospital is feasible in medically equipped ambulances without an apparent increase in bleeding. Furthermore, prehospital clopidogrel tended to show better early coronary patency compared to placebo, a result consistent with that observed in patients randomized in-hospital in the CLARITY-TIMI 28 trial.

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Correspondence to Freek W. A. Verheugt.

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Verheugt, F.W.A., Montalescot, G., Sabatine, M.S. et al. Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation acute myocardial infarction: a substudy of the randomized double blind CLARITY-TIMI 28 trial. J Thromb Thrombolysis 23, 173–179 (2007). https://doi.org/10.1007/s11239-006-9047-y

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  • DOI: https://doi.org/10.1007/s11239-006-9047-y

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