Correspondence
Prehospital Thrombolytic Therapy for Myocardial Infarction
N Engl J Med 1994; 330:290-291January 27, 1994
- Article
To the Editor:
The study of prehospital thrombolytic therapy by the European Myocardial Infarction Project (EMIP) Group, published in the August 5 issue of the Journal,1 showed a nonsignificant reduction in mortality among patients treated before admission (the prehospital group) as compared with those who underwent thrombolysis in the hospital. The number of patients recruited was limited, but this may not be the only reason that the difference in mortality was not statistically significant.
The relation between the benefit derived from thrombolytic therapy and the time of onset of myocardial infarction is not linear. It has been shown2 that thrombolytic therapy is most effective when given within the first hour after the onset of chest pain, reducing mortality by more than 50 percent. Thereafter this benefit drops sharply and levels out. This evidence implies that the difference in mortality would be greatest if treatment within the first hour were compared with treatment at other times. The difference in mortality at points after the first hour may not be large, and therefore a very large number of patients would be required for a difference to become significant. It follows, therefore, that for any trial comparing prehospital with in-hospital thrombolysis to show a significant difference in clinical outcome, attempts have to be made to treat the majority of the prehospital group within the first hour.
In this trial,1 more than half the patients in the prehospital group received thrombolysis after the first hour of chest pain. This may also explain the relatively high mortality in this group (9.7 percent), comparable to the mortality in trials of in-hospital thrombolysis such as the Third International Study of Infarct Survival (mortality 35 days after anistreplase treatment, 10.5 percent)3. The EMIP trial does not mention the reasons behind the delays in treatment. Clearly, there may be many factors involved, some of which may relate to the trial's design and some of which may not, such as patients' not calling for help soon enough. It is very important to identify these factors so that measures can be taken to minimize any delays. The rationale for early, prehospital thrombolytic therapy is faster recanalization and therefore more rapid reperfusion of the infarct-related artery, since it is generally accepted, and has recently been confirmed in the trial by the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico,4 that early and sustained complete patency of this artery is the most crucial factor in preventing death after myocardial infarction.
4 ReferencesFarzin Fath-Ordoubadi, M.R.C.P.
Charing Cross Hospital, London W6 8RF, United Kingdom1
The European Myocardial Infarction Project Group
Full Text | Web of Science | Medline2
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group
Web of Science | Medline3
ISIS-3 (Third International Study of Infarct Survival) Collaborative Group
CrossRef | Web of Science | Medline4
The GUSTO Investigators
Full Text | Web of Science | Medline
To the Editor:
The EMIP investigators reported an increased incidence of ventricular fibrillation among patients who received thrombolytic therapy before hospitalization, as compared with those receiving placebo, raising concern that the prehospital use of thrombolytic agents may be associated with a higher incidence of ventricular fibrillation. To avoid concluding that an apparent increased risk of ventricular fibrillation justifies waiting until hospitalization to initiate thrombolytic therapy, it is important to place the results of this trial in perspective. Although there was 1 excess episode of early ventricular fibrillation per 100 patients in the prehospital group, there were 14 fewer deaths in the same group at 30 days.
One possible interpretation of the higher incidence of ventricular fibrillation in the prehospital group is that the early use of thrombolytic therapy for myocardial infarction is associated with a higher incidence of early reperfusion arrhythmias, which were detected in the EMIP trial because of early monitoring. Although reperfusion-related ventricular fibrillation has been reported in experimental models, it has not been definitively shown to occur in patients. In a recent meta-analysis of thrombolytic trials (median time to treatment, 3.6 hours), we reported no significant difference in the risk of ventricular fibrillation associated with thrombolysis or administration of placebo during the first 6 hours (odds ratio, 0.98; 95 percent confidence interval, 0.6 to 1.6); there was a significant decrease in the risk of ventricular fibrillation in the group given thrombolytic treatment at any time during hospitalization (odds ratio, 0.83; 95 percent confidence interval, 0.76 to 0.90)1.
Several potential confounding influences that may have affected the reported incidence of early ventricular fibrillation in the EMIP trial should be considered. The risk of early ventricular fibrillation may be altered by concomitant therapy (with beta-blockers, diuretics, or antiarrhythmic agents) or by electrolyte deficiencies (of potassium or magnesium). The possibilities of an imbalance in the distribution of these covariates between the early-thrombolysis and placebo groups, or a difference in their effects on the two groups, cannot be excluded. Furthermore, the authors report a statistically significant 60 percent increase in the incidence of shock before hospitalization in the early-thrombolysis group (Table 2 of their article). This raises the possibility that the higher incidence of early ventricular fibrillation reported in this group may have been due to an excess of ventricular fibrillation in patients with shock (secondary ventricular fibrillation). Such terminal-phase arrhythmias are unlikely to be related to reperfusion and may entirely explain the increased incidence of early ventricular fibrillation in the prehospital group2.
2 ReferencesScott D. Solomon, M.D.
Elliott Antman, M.D.
Brigham and Women's Hospital, Boston, MA 021151
Ventricular arrhythmias in trials of thrombolytic therapy for acute myocardial infarction: a meta-analysis. Circulation 1993 (in press).
2
Campbell RW . Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction. Am J Cardiol 1983;52:55C-59C
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Jens Scholz, Maria Fassmann, Andreas Schuchert, Stefanie Klimmeck, Britta Goldmann, Christian W. Hamm, Jochen Schulte am Esch. (1999) Troponin-T-Schnelltest im Notarztwagen Einflu
auf Diagnose und Therapie. Unfallchirurgie 25:2, 78-83
CrossRef
