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Three Part Question

In [adults with an acute myocardial infarction] does [early administration of aspirin] decrease [mortality]?

Clinical Scenario

A 49-year-old man presents to the Emergency Department with a three-hour history of central crushing chest pain. An ECG reveals an acute inferior myocardial infarction. You know that the administration of aspirin reduces future morbidity and mortality but wonder if the administration of aspirin is as time critical as thrombolysis.

Search Strategy

Medline 1966-9/00 using the OVID interface.
[(exp myocardial infarction OR myocardial infarction.mp OR heart attack.mp) AND (exp aspirin OR aspirin.mp OR salicylic acid.mp )]AND maximally sensitive RCT filter LIMIT to human and english.

Search Outcome

295 papers found of which 294 were either irrelevant or of insufficient quality. The remaining paper is shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
ISIS-2, 1988, multinational.	17,187 patients within 24 hours of suspected MI. IV streptokinase or aspirin or both or neither Subgroup analysis mortality v time of aspirin administration from onset of symptoms at 0-4 h, 5-12 h, 13-24 h	PRCT	Overall vascular mortality	4% relative risk reduction (0-4 h v 5-12 h v 13-24 h, p=NS)	Not the primary aim of the study, so very hard to extract data.
			Odds of death at 5 weeks v placebo
			0-4 h	0.75 (SD=0.07)
			5-12 h	0.79 (SD=0.07)
			13-24 h	0.79 (SD=0.12)

Comment(s)

While this paper does not reach statistical significance it does show a trend in reduction of mortality with early aspirin administration. Taking this into account and the large standard deviations given a true difference may indeed exist. Other available data looks at the combined effect of early thrombolysis and aspirin on the reduction of mortality and the data here are clear that the earlier the administration the greater the reduction in mortality and morbidity. Evidence exists to show that pharmacologically aspirin has maximal effect within one hour of oral administration, although whether this translates into the clinical setting is unclear. The availability of aspirin, its cost, ease of administration, and the minimal risks associated with a single dose make it an ideal immediate treatment to be given pre hospital. The available data however suggests that this is not so time critical, that other factors cannot be taken into consideration e.g. gastrointestinal upset, respiratory contraindications etc.

Clinical Bottom Line

In an acute myocardial infarction, aspirin should be administered as early as possible.

References

1. ISIS Collaborative Group Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of acute myocardial infarction: ISIS-2. The Lancet 1988;2:349–60.