Prehospital thrombolysis for suspected myocardial infarction decreased 30-day cardiac death
ACP J Club. 1994 Jan-Feb;120:6. doi:10.7326/ACPJC-1994-120-1-006
The European Myocardial Infarction Project Group. Prehospital thrombolytic therapy in patients with suspected acute myocardial infarction. N Engl J Med. 1993 Aug 5;329:383-9.
To compare the efficacy and safety of thrombolytic therapy given outside the hospital with thrombolytic therapy given after hospitalization to patients with suspected acute myocardial infarction (MI).
Randomized, double-blind, placebo-controlled trial with 30-day follow-up.
163 hospitals in Europe and Canada.
5469 patients seen within 6 hours of typical onset of chest pain who had a qualifying 12-lead electrocardiogram (ECG). Exclusion criteria were concurrent anticoagulant therapy, although antiplatelet therapy was allowed; hemorrhagic diathesis or a recently active peptic ulcer; stroke, surgery, or major trauma within 6 months; external cardiac massage; pain lasting for < 30 minutes; hypertension; possibility of pregnancy; or coronary angioplasty within 2 weeks. Follow-up was 99.8%.
The first injection (either anistreplase, 30 units, or placebo) was given intravenously before transfer to the hospital. The second injection (placebo if anistreplase already given or vice versa) was given after hospital confirmation of MI. 2750 patients were randomized to the prehospital group and 2719 to the hospital group.
Main outcome measures
Total mortality at 30 days. Secondary end points were cardiac death, stroke, hemorrhage, heart failure, arrhythmias, and adverse events.
The median length of time between symptom onset and prehospital treatment was 130 minutes and for in-hospital treatment was 190 minutes. MI was confirmed in 87.2% of patients. A trend toward decreased 30-day mortality occurred for the prehospital group (P = 0.08) (Table). Compared with patients in the hospital group, patients in the prehospital group had decreased cardiac death (P < 0.05) (Table). The groups did not differ for incidence of complications, hemorrhage, strokes, fatal and nonfatal events, adverse events, cardiac arrest, or shock.
Patients with a suspected myocardial infarction had a decreased 30-day mortality from cardiac causes, but not decreased total mortality, when they received thrombolytic therapy before hospital admission compared with patients who received thrombolytic therapy after hospitalization.
Sources of funding: European Economic Community and SmithKline Beecham Pharmaceuticals.
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Table. Prehospital vs in-hospital thrombolytic therapy for suspected myocardial infarction*
|Outcomes at 30 d||Prehospital||In-hospital||RRR (95% CI)||NNT (CI)|
|Total mortality||9.7%||11.1%||13% (-1 to 26)||Not significant|
|Cardiac death||8.3%||9.8%||16% (0.9 to 29)||65 (33 to 12603)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
The study provides additional evidence on the feasibility of initiating thrombolytic therapy quickly before hospitalization. Prehospital treatment has resulted in the most marked improvement in survival when in-hospital treatment was initiated > 90 minutes after prehospital evaluation. In the smaller Myocardial Infarction Triage and Intervention (MITI) trial (1), a survival benefit for prehospital initiation of alteplase could not be shown, but only 30 to 60 minutes were gained by prehospital treatment. These results add to evidence from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardio (GISSI) subgroup analysis (2) and from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial (GUSTO) (3) that the benefits of thrombolysis have a marked time dependence; the lowest mortality was seen in patients who received therapy within the first 4 hours.
Although anistreplase was used in this study, it has no particular advantage over streptokinase, other than bolus administration. The Third International Study of Infarct Survival (ISIS-3) (4) showed more cerebral hemorrhage with anistreplase than with streptokinase. The results of the GUSTO trial suggest that a front-loaded regimen of tissue plasminogen activator may be preferable for treating patients with ST elevation within the first 4 hours of the onset of symptoms (3). Both streptokinase and alteplase must be infused; thus, prehospital treatment is more difficult.
Prehospital thrombolysis accelerates initiation of treatment and, despite reperfusion arrhythmias, is safe when done by trained personnel. Diagnosis of infarction may not require a physician on site if facilities are available for telemetry of 12-lead ECGs (1). For most hospitals, however, the current emphasis should be on rapid diagnosis and initiation of treatment within 20 to 30 minutes of patient arrival.
Paul R. Eisenberg, MD
Washington University School of MedicineSt. Louis, Missouri, USA
4. ISIS-3(Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. Lancet. 1992;339:753-70.