Authors' objectives

To compare in-hospital mortality for prehospital versus in-hospital thrombolysis for acute myocardial infarction (AMI).

Searching

Searches were conducted of MEDLINE, EMBASE, and Science Citation Index (1982 to 1999); Dissertation Abstracts (1987 to 1999); and Current Contents (1994 to 1999). Key terms were: 'thrombolysis'; 'thrombolytic therapy'; 'prehospital'; 'acute myocardial infarction'; combined with the Cochrane search strategy (see Other Publications of Related Interest no.1). Bibliographies of texts and journal articles were handsearched and the National Institutes of Health website was reviewed for grants pertaining to the subject. Primary authors and manufacturers of thrombolytic agents were contacted for knowledge of unpublished studies.

Study selection

Assessment of study quality

The Detsky scale was used to assess and score validity (see Other Publications of Related Interest no.2). Two reviewers blinded to author's name, title, introduction, discussion and journal, independently assessed validity. Inter-rater agreement was evaluated using the interclass correlation coefficient for random raters. Interclass correlation coefficient for random raters was 0.73.

Data extraction

Two reviewers blinded to author's name, title, and journal, extracted the following data: author; year of publication; provider; time from onset to thrombolysis; outcome; and inclusion and exclusion criteria. Abstracted data was confirmed by reviewer consensus and then sent to the primary author for verification if necessary.

Methods of synthesis

Results of the review

Six randomised placebo-controlled trials (RCTs) with 6,434 patients and three follow-up studies were included.

Quality assessment. Scores ranged from 0.43 to 0.91 from a maximum possible score of 1. Three RCTs scored 0.78 or more. The majority of studies failed to report concealment of allocation and blinding of outcome assessment. Homogeneity There was no evidence of heterogeneity for short-term hospital mortality (P = 0.9 and plot of mortality for prehospital vs in-hospital thrombolysis showed consistency between outcomes) or for 2-year mortality (P = 0.86).Homogeneity was poor for 1-year mortality (P = 0.4). Mortality. Overall short-term hospital mortality (six RCTs): prehospital thrombolysis significantly reduced short-term mortality. Pooled OR = 0.83 (95% CI: 0.70, 0.98; P = 0.03). Data were insufficient to evaluate mortality at 30 days and 60 days. 1-year mortality (two RCTs): no significant difference between prehospital and in-hospital thrombolysis. Pooled OR = 0.68 (95% CI: 0.26, 1.80; P = 0.44). 2-year mortality (two RCTs): no significant difference between prehospital and in-hospital thrombolysis. Pooled OR = 1.18 (95% CI: 0.62, 2.22; P = 0.62). 5-year mortality (one RCT): significantly higher mean survival in the prehospital thrombolysis group. Difference 208 days (95% CI: 42, 374; P < 0.03). Secondary outcomes: these were defined inconsistently and variably reported. Sensitivity analysis. Analysis limited to higher quality trials (three RCTs): results were similar to overall results with pooled OR = 0.84 (95% CI: 0.70, 0.99). Influence of provider qualifications: assessed by considering only studies of mobile intensive care units with administration by intensive care physician (four RCTs): results were similar to overall results with pooled OR = 0.80 (95% CI: 0.72, 1.02). Provider by treatment group effect: this was not significant (P =0.16). Provider on mortality effect: this was not significant (P = 0.58). Time to thrombolysis treatment. Prehospital thrombolysis significantly improved time to needle for thrombolysis: the time difference and standard error (SE) to thrombolysis between the prehospital group (104 minutes, SE = 7) and the in-hospital group (162 minutes, SE = 16) was 60 minutes (P =0.007). Re-analysis after exclusion of one study set in towns and villages at distances that compromised transfer time: the time difference to thrombolysis between the prehospital group (104.67 minutes) and the in-hospital group (149.33 minutes) was 45 minutes (P = 0.01).

Authors' conclusions

Prehospital thrombolysis for AMI significantly decreases the time to thrombolysis and all-cause hospital mortality.

CRD commentary

The aims were stated and inclusion criteria defined in terms of study design, participants, intervention and outcomes. The process of study selection was described and inter-reviewers agreement levels reported. Several sources were searched and attempts were made to locate unpublished studies, though it was not stated whether any language restrictions were applied. The methods used to assess and score validity were described. Relevant details of the included studies were presented in tabular format. Heterogeneity was discussed and assessed statistically and results were pooled where appropriate. Sensitivity analysis was performed to investigate the influence of various factors, including study validity, on the results. This thorough review was clearly written and presented. Evidence supports the authors' conclusions.

Implications of the review for practice and research

Practice: The authors state that there is sufficient evidence to suggest that prehospital thrombolysis reduces the delay to treatment in settings with long transit times, and that the choice of thrombolytic agent remains less important than making the correct diagnosis and rapid and safe administration of the thrombolytic agent.

Research: The authors state that in urban settings with relatively short transit times, prehospital thrombolysis should be evaluated in comparison with 12-lead ECG interpretations with advance notification and rapid transportation to definitive care.

Bibliographic details

Morrison L J, Verbeek P R, McDonald A C, Sawadsky B V, Cook D J. Mortality and prehospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA 2000; 283(20): 2686-2692. [PubMed: 10819952]

Original Paper URL

http://jama.ama-assn.org/

Other publications of related interest

1. Mulrow CD, Oxman AD, editors. Cochrane Collaboration Handbook. In: The Cochrane Library, 1997. Oxford: Update Software. Updated quarterly. 2. Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbe KA. Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol 1992;45:255-65. 3. Breslow NE, Day NE. Statistical methods in cancer research. Lyon: IARC Scientific Publications; 1980.

These additional published commentaries may also be of interest. Kellett MA. Review: prehospital thrombolysis for acute myocardial infarction decreases short term hospital mortality. Evid Based Med 2000;6:12. Prehospital thrombolysis for MI. Bandolier 2000;77:6.

Indexing Status

Subject indexing assigned by NLM

MeSH

Emergency Medical Services; Emergency Service, Hospital; Fibrinolytic Agents /therapeutic use; Hospital Mortality; Humans; Myocardial Infarction /drug therapy /mortality; Randomized Controlled Trials as Topic; Survival Analysis; Thrombolytic Therapy; Time Factors

AccessionNumber

12000008661

Database entry date

31/07/2001

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.