Quantification of the benefit of earlier thrombolytic therapy: five-year results of the Grampian Region Early Anistreplase Trial (GREAT).
OBJECTIVE
This report presents the 5-year results of the Grampian Region Early Anistreplase Trial (GREAT) and quantifies the benefit of earlier thrombolysis in terms that are generally applicable.


BACKGROUND
Although it is accepted that the earlier thrombolytic therapy is given for acute myocardial infarction the greater the benefit, there are widely differing estimates of the magnitude of the time-related benefit of thrombolysis because of inappropriate trial design and analysis.


METHODS
In a previously reported randomized trial, anistreplase (30 U) was given intravenously either before hospital admission or in the hospital, at a median time of 105 and 240 min, respectively, after onset of symptoms. Intention to treat and multivariate analyses of the 5-year results were performed.


RESULTS
By 5 years, 41 (25%) of 163 patients had died in the prehospital treatment group compared with 53 (36%) of 148 in the hospital treatment group (log-rank test, p < 0.025). Delaying thrombolytic treatment by 1 h increases the hazard ratio of death by 20%, equivalent to the loss of 43/1,000 lives within the next 5 years (95% confidence interval 7 to 88, p = 0.012). Delaying thrombolytic treatment by 30 min reduces the average expectation of life by approximately 1 year.


CONCLUSIONS
The magnitude of the benefit from earlier thrombolysis is such that giving thrombolytic therapy to patients with acute myocardial infarction should be accorded the same degree of urgency as treatment of cardiac arrest. Policies should be developed for giving thrombolytic therapy on-site if practicable and by the first qualified person to see the patient.
Rawles
J M
JM
Medicines Assessment Research Unit, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016255:Anistreplase / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012606:Scotland; D016019:Survival Analysis; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D016255:Anistreplase