Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis.

PURPOSE

To compare the efficacy and safety of different aspirin dosages in trials with patients at increased risk of vascular disease.

DATA SOURCES

Pertinent studies were selected using MEDLINE (1966 through 1992), weekly reviews of Current Contents (1970 through 1992), and references from review articles and editorials.

STUDY SELECTION

Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo.

METHODS

The Mantel-Haenszel method of pooling odds ratios and metaregression involving log odds ratio (and the risk difference) on aspirin dosage, adjusting for the control rate and the mean length of follow up of the studies.

RESULTS

For all patients and for subgroups of patients with previous vascular conditions, there was no relationship between dose and vascular events. For all patients, a dose-response relation was not found with gastrointestinal hemorrhages and hemorrhagic stroke, but was found with gastrointestinal symptoms and withdrawals from side effects. For every 25 mg/day increase in aspirin dosage, the odds ratio of gastrointestinal symptoms and withdrawals increased, respectively, by 0.87% (99% Cl, 0.18 to 1.57%) and 0.94% (99% Cl, 0.06 to 1.82%). The corresponding absolute risk increases were 0.58 and 0.78 per 1,000 patients.

CONCLUSIONS

Direct and indirect comparisons of high-risk patients suggest no statistical differences in efficacy, gastrointestinal bleeds, and hemorrhagic strokes across aspirin dosages. These comparisons, however, suggest decreased risk of gastrointestinal symptoms and of withdrawals with lower doses of aspirin. More direct comparison studies are warranted that should contrast the benefits and risks to determine the net benefit.