Aspirin in the Treatment and Prevention of Cardiovascular Disease: Past and Current Perspectives and Future Directions
The following are 10 points to remember about aspirin in the treatment and prevention of cardiovascular disease:
1. The most plausible biological mechanism for the action of aspirin in the reduction of risks of occlusive vascular events is its ability in platelets to irreversibly acetylate the active site of cyclooxygenase required for the production of thromboxane A2, a powerful promoter of aggregation.
2. Aspirin, in doses from 81 mg to 1200 mg daily, also increases endothelial-derived nitric oxide, which may provide added benefit including a reduction in the progression of atherosclerosis.
3. Aspirin for secondary prevention was reviewed in 195 randomized trials of antiplatelet therapy, principally with aspirin, among more than 135,000 high-risk patients with prior evidence of cardiovascular disease, in stable and unstable coronary and cerebral vascular disease, and post-revascularization. Aspirin produced a 22% reduction in risk of subsequent vascular events; an absolute reduction of 36 vascular events per 1,000 patients with a prior myocardial infarction or previous stroke or transient ischemic attack treated at approximately 28 months.
4. In secondary prevention, there is no difference in efficacy or safety of aspirin, in indirect comparisons as well as direct comparisons, between doses of 75-150 mg/day and 160-325 mg/day.
5. For acute occlusive strokes, a meta-analysis showed a statistically significant and clinically important 11% reduction in vascular events, as well as nonfatal stroke and vascular deaths. For every 1,000 patients with acute stroke, treatment with aspirin avoided nine vascular events. For patients with acute occlusive stroke, aspirin should be administered promptly and continued long-term.
6. In a comprehensive meta-analysis of six major primary prevention trials, in apparently healthy people, aspirin did not show a significant reduction in vascular mortality, as had been shown in the Physicians Health Study.
7. While there are similarities in proportional reductions (relative risk), the absolute benefits of aspirin are far smaller in the primary than in the secondary prevention trials due to the far lower absolute risks in the apparently healthy subjects.
8. In the primary prevention trials, there was no modification of benefit of aspirin by risk factors or gender.
9. Until the results of ongoing trials of aspirin in intermediate-risk subjects are published, judgments about prescribing long-term aspirin therapy for apparently healthy individuals at intermediate cardiovascular risk need to be made on a case-by-case basis.
10. Further research, including direct randomized trials of the two most widely used doses of aspirin, 81 mg and 325 mg, is needed to assess the effect of aspirin on the progression of atherosclerosis after 2 years.
The value of aspirin for primary prevention in the era of statins and treatment of hypertension is very difficult to measure. It is unlikely that the answer to aspirin indications and optimal dosing will be available prior to the demonstration that novel antiplatelet or antithrombotic agents provide greater benefit.
Keywords: Myocardial Infarction, Stroke, Atherosclerosis, Ischemic Attack, Transient, Thromboxane A2, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Blood Platelets, Fibrinolytic Agents, Nitric Oxide, Primary Prevention, Secondary Prevention, Cyclooxygenase 1, Cardiovascular Diseases, Hypertension, Prostaglandin-Endoperoxide Synthases
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