Ragavendra R. Baliga, M.D
Assistant Professor
Division of Cardiology
University Of Michigan

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Question 13 of 39:

Aspirin used alone, in the treatment of evolving MI, has been shown conclusively to reduce 35-day mortality by at least one-fifth.

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The 2nd International Study of Infarct Survival (ISIS-2) has shown conclusively the efficacy of aspirin alone for the treatment of acute MI in reducing 35-day mortality by 23%[1]. When combined with streptokinase, the reduction in mortality was 42%.

In patients with suspected acute MI aspirin should be given promptly and certainly within the first 24 hours at a dose between 160 to 325 mg and continued daily indefinitely.

Unlike fibrinolytic agents, there is little evidence for time-dependent effect of aspirin on early mortality. However, data does support the premise that a chewable aspirin is absorbed more quickly than one swallowed in early hours after infarction, particularly after opiate therapy.

Thus use of aspirin is contraindicated in those with a hypersensitivity to salicylate and should be used with caution in patients with active ulcer disease. Aspirin suppositories (325 mg) can be used safely and are the recommended route of administration for patients with severe nausea and vomiting or know upper gastrointestinal disorders.

Mechanism of action of aspirin: In platelets, aspirin prevents formation of thromboxane A2, a substance that induces platelet aggregation. Because platelets are unable to generate new cyclo-oxygenase, enzyme inhibition lasts for the life of the cell or ~10 days. In vascular endothelial cells aspirin prevents the synthesis of prostacyclin, which inhibits platelet aggregation. Endothelial cells can recover cyclo-oxygenase synthesis so that the inhibitory effects of aspirin may be of shorter duration than with platelets.

The long-term use of aspirin in the postinfarct patient also results in a significant reduction in subsequent mortality. In six randomized, placebo-controlled trials in which patients were randomly selected between 1 week and 7 years after the initial infarct, meta-analysis reveals a reduction in vascular mortality of 13% among those randomly assigned to aspirin with a reduction in nonfatal reinfarction of 31% and nonfatal stroke of 42%. Although all of these trials involved the use of aspirin in doses ranging from 300 to 1500 mg/d, a recent trial of patients with chronic stable angina pectoris in which aspirin 75 mg/d was used demonstrated a significant reduction of 34% in the primary end point of nonfatal MI and sudden death. This suggests long-term use of aspirin in the postinfarction patient in a dose as low as 75 mg/d can be effective, with the likelihood that side effects can be reduced.

Other antiplatelet agents such as sulfinpyrazone and dipyridamole have been used in the postinfarct patient, but there is no evidence from these clinical trials that they were any more efficacious than aspirin alone. Ticlopidine, an antiplatelet agent that has been effectively used in unstable angina and cerebrovascular disease, has not been studied in major clinical trials involving patients with acute MI.

Reference:

1. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction. Lancet 1988;2:349-360.