Elsevier

American Heart Journal

Volume 164, Issue 2, August 2012, Pages 153-162.e5
American Heart Journal

Curriculum in Cardiology
Is there an association between aspirin dosing and cardiac and bleeding events after treatment of acute coronary syndrome? A systematic review of the literature

https://doi.org/10.1016/j.ahj.2012.04.001Get rights and content

Background

Current acetylsalicylic acid (ASA) dosing algorithms for the prevention of secondary thrombotic events in acute coronary syndrome (ACS) patients are inconsistent and lack sufficient data support.

Methods

We performed a systematic review of the literature for studies that assessed clinical outcomes in patients with ACS following coronary stent insertion (SI) or medical treatment (MT). Acetylsalicylic acid dosing was stratified into low- (< 160 mg) and high- (≥ 160 mg) dose categories. Outcomes were assessed at 1, 6, and 12 months and included major bleeding, myocardial infarction, and all-cause death. A random-effects meta-analysis was used to estimate the value of the mean for each outcome variable.

Results

Of 12,472 publications identified, 136 studies with 289,330 patients were analyzed. In the 1-month SI analysis, proportions of patients (95% CI) in the low- and high-dose ASA categories experiencing major bleeding were 2.1% (1.5-2.6) and 1.9% (0.0-3.8); proportions with myocardial infarction were 2.1% (1.3-2.8) and 1.8% (0.9-2.6); and proportions of all-cause death were 2.8% (2.2-3.4) and 2.4% (1.3-3.5), respectively. Results were similar in the MT analysis, except that major bleeding rates for low and high doses were 1.7% (1.3-2.2) and 4.0% (2.2-5.8), respectively. Regression analyses suggested that the proportion of patients reporting each of the outcomes evaluated were not significantly different between the low- and high-dose categories, with the exception of the 1-month major bleeding following MT.

Conclusions

Our results suggest no improved clinical outcomes associated with higher ASA maintenance doses in ACS patients receiving SI or MT. In the MT analysis, there was more major bleeding in the first month after an ACS event with high-dose ASA.

Section snippets

Background

Acetylsalicylic acid (ASA) maintenance therapy is recommended in combination with adenosine diphosphate (ADP) inhibitors for the prevention of secondary thrombotic events in patients with acute coronary syndrome (ACS). Patients with a higher risk of future cardiac events are frequently prescribed high-dose ASA (325 mg/d) regimens, whereas patients with a lower risk or those with an increased risk of bleeding receive lower doses.1 The higher ASA doses are prescribed with the hope that they will

Objective

The objective of this systematic review and meta-analysis was to examine the literature on clinical trials and observational studies to better understand the evidence supporting the efficacy and safety of ASA dosing (with or without ADP inhibitors) in patients with ACS who underwent stent insertion (SI), coronary artery bypass grafting (CABG), or medical treatment (MT).

Search strategy

We performed 3 separate literature searches that included both electronic and manual components. Each search was designed to identify publications that evaluated patients with ACS who received treatment with SI, CABG, or MT. The electronic searches were performed in MEDLINE (via PubMed), EMBASE, and Current Contents; and all duplicate abstracts were removed before screening. Based on the availability of publications on the therapies of interest, the searches were restricted to January 1, 1985,

Search yields

The literature search for the SI group yielded 4,605 citations. Of these, 981 citations passed abstract screening and underwent full article screening; 93 passed the screening and were accepted for review. The review identified 25 publications that reported on previously reported patient populations (“related publications”), leaving 68 primary publications for analysis.

The literature search for the CABG group yielded 2,058 citations. Of these, 353 citations passed abstract screening and

Discussion

This is the first meta-analysis to our knowledge that investigates the role of maintenance aspirin dose in patients with ACS and the occurrence of thrombotic or bleeding events following SI or MT. We analyzed data from 136 primary publications and 289,330 patients; and the results suggest that there was no difference in the rate of thrombotic events between the ASA doses studied, even after adjusting for select confounders.

There were only 2 randomized clinical trials that directly addressed

Conclusion

In conclusion, our analyses suggest that there are no differences in clinical outcomes between low- and high-dose ASA after SI or during MT. In addition, high-dose ASA may be associated with higher rates of major bleeding in patients during MT.

Acknowledgement

We thank John Tumas, MS, ELS, of AstraZeneca for providing editorial assistance.

References (18)

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James A. de Lemos, MD, served as guest editor for this article.

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