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J Cancer 2020; 11(21):6460-6473. doi:10.7150/jca.49001 This issue Cite

Research Paper

Long-term aspirin use for primary cancer prevention: An updated systematic review and subgroup meta-analysis of 29 randomized clinical trials

Qibiao Wu^1,2✉, Xiaojun Yao^1,2#, Hongwei Chen^1,3#, Zhengtang Liu^4#, Ting Li^1,2, Xingxing Fan^1,2, Guilin Zhang^1,2, Lili Yu^1,2, Min Chen^1,2, Cong Xu^1,2, Ruonan Zhang^1,2,5,6, Bi Chen^1,2,5,6, Xinbing Sui^5,6✉, Elaine Lai-Han Leung^1,2✉

1. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
2. Faculty of Chinese Medicine; Macau University of Science and Technology, Macau, China.
3. Faculty of Medicine; Macau University of Science and Technology, Macau, China.
4. Department of Geriatrics, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, P.R. China.
5. Holistic Integrative Pharmacy Institutes and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
6. Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China.
#Equal contributors and co-first authors.

✉ Corresponding authors: E-mails: hzzjuedu.cn (X. Sui), lhleungedu.mo (E. Leung), qbwuedu.mo (Q. Wu).

Abstract

Background and objective: Long-term aspirin use for the primary prevention of cancer remains controversial, and variations in the effect of aspirin use on cancer outcomes by aspirin dose, follow-up duration, or study population have never been systematically evaluated. The objective of this study was to evaluate the effect of aspirin on primary cancer prevention and to determine whether the effect differed according to aspirin dose, follow-up duration, or study population.

Materials and methods: Seven electronic databases were searched from inception to September 30, 2019. Randomized clinical trials (RCTs) that compared aspirin use versus no aspirin use in participants without pre-existing cancer and reported cancer outcomes were selected. Data were screened and extracted by different investigators. Analyses were performed using Review Manager 5.3 and Comprehensive Meta-Analysis 2.0. Total cancer incidence was defined as the primary clinical endpoint. Total cancer mortality, all-cause mortality, major bleeding, and total bleeding events were the secondary outcomes. Subgroup analyses were conducted based on aspirin dose, follow-up duration, and study populations.

Results: Twenty-nine RCTs that randomized 200,679 participants were included. Compared with no aspirin, aspirin use was not associated with significant reductions in total cancer incidence (RR = 1.01, 95% CI: 0.97 to 1.04, P = 0.72), total cancer mortality (RR = 1.00, 95% CI: 0.93 to 1.07, P = 0.90), or all-cause mortality (RR = 0.98, 95% CI: 0.94 to 1.02, P =0.31); however, aspirin use was associated with a 44% increase in the risk of major bleeding (RR = 1.44, 95% CI: 1.32 to 1.57, P < 0.00001) and a 52% increase in the risk of total bleeding events (RR = 1.52, 95% CI: 1.33 to 1.74, P < 0.00001). Subgroup analyses demonstrated consistent results.

Conclusions: Long-term aspirin use in individuals without pre-existing cancer was not associated with a significant reduction in total cancer incidence, cancer mortality, or all-cause mortality; however, aspirin use was associated with a significant increase in the risk of bleeding. Therefore, aspirin is not an appropriate choice for the primary cancer prevention.

Keywords: long-term, aspirin, cancer, primary prevention, systematic review, subgroup meta-analysis, randomized clinical trials

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