Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 7/2019

01-07-2019 | Warfarin | Review – Clinical Oncology

Safety and efficacy of aspirin for primary prevention of cancer: a meta-analysis of randomized controlled trials

Authors: Tarek Haykal, Mahmoud Barbarawi, Yazan Zayed, Anitha Yelangi, Harsukh Dhillon, Sowmya Goranta, Babikir Kheiri, Adam Chahine, Varun Samji, Josiane Kerbage, Khalil Katato, Ghassan Bachuwa

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2019

Login to get access

Abstract

Background

In the United States, cancer is the second leading cause of mortality, and millions more battle cancer worldwide. As such, primary prevention of cancer is a major interest globally. Aspirin has been studied as a primary prevention method for multiple diseases, mainly cardiovascular disease and various forms of cancer. The role of aspirin as a primary prevention of cancer is still controversial and may be more beneficial in certain cancers over others. With rapidly surfacing large randomized controlled trials (RCTs) studying this subject, we aimed to evaluate the efficacy and safety of aspirin as a primary prophylaxis for cancer.

Methods

A comprehensive electronic database search was conducted for all RCTs that compared aspirin versus placebo for the prevention of any type of disease, and where cancer incidence or mortality was reported. The primary outcome was cancerrelated mortality. Secondary outcomes were cancer incidence, all-cause mortality, major bleeding, any bleeding and gastrointestinal (GI) bleeding. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up period.

Results

We included 16 RCTs with 104,018 total patients, mean age of 60.51 years, mean follow-up of 5.48 years, and a male percentage of 38.72%. We found that aspirin was not associated with a significant reduction of cancer-related mortality compared with placebo (RR 0.99; 95% CI: 0.87–1.12; P = 0.85: I2 = 41%). Compared with placebo, aspirin was not associated with significant reduction of all-cause mortality (RR 0.97; 95% CI: 0.92–1.02; P = 0.19; I2 = 13%) or cancer incidence (RR: 0.98; 95% CI: 0.92–1.04; P = 0.43; I2 = 16%). However, aspirin treatment was associated with significantly increased risks of any bleeding (RR 1.63; 95% CI: 1.31–2.03; P < 0.01), major bleeding (RR 1.41; 95% CI: 1.26–1.57; P < 0.01), and GI bleeding (RR 1.85; 95% CI: 1.38–2.48; P < 0.01) compared with placebo.

Conclusion

Our study did not find any significant reductions in cancer-related mortality or cancer incidence when compared aspirin use with placebo or no aspirin. Our study also highlights that the use of aspirin for primary prevention of cancer was found to cause higher rates of bleeding (any bleeding, major bleeding, and GI bleeding) compared to placebo or no aspirin at the longest follow-up period with no significant benefit in cancer primary prevention.
Literature
go back to reference Belch J, MacCuish A, Campbell I et al (2008) The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 337:a1840CrossRefPubMedPubMedCentral Belch J, MacCuish A, Campbell I et al (2008) The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 337:a1840CrossRefPubMedPubMedCentral
go back to reference Brighton TA, Eikelboom JW, Mann K et al (2012) Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 367:1979–1987CrossRefPubMed Brighton TA, Eikelboom JW, Mann K et al (2012) Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 367:1979–1987CrossRefPubMed
go back to reference Chubak J, Whitlock EP, Williams SB, Kamineni A, Burda BU, Buistand DS, Anderson ML (2016) Annals of internal medicine aspirin for the prevention of cancer incidence and mortality : systematic evidence reviews for the U.S. Preventive Services. Ann Int Med 164(12):814–825CrossRefPubMed Chubak J, Whitlock EP, Williams SB, Kamineni A, Burda BU, Buistand DS, Anderson ML (2016) Annals of internal medicine aspirin for the prevention of cancer incidence and mortality : systematic evidence reviews for the U.S. Preventive Services. Ann Int Med 164(12):814–825CrossRefPubMed
go back to reference Collaborative Group of the Primary Prevention Project (2001) Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 357:89–95CrossRef Collaborative Group of the Primary Prevention Project (2001) Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 357:89–95CrossRef
go back to reference Cook NR, Lee IM, Zhang SM et al (2013) Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med 159:77–85CrossRefPubMedPubMedCentral Cook NR, Lee IM, Zhang SM et al (2013) Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med 159:77–85CrossRefPubMedPubMedCentral
go back to reference ETDRS Investigators (1992) Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 14. JAMA 268:1292–1300CrossRef ETDRS Investigators (1992) Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 14. JAMA 268:1292–1300CrossRef
go back to reference Farrell B, Godwin J, Richards S, Warlow C (1991) The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 54:1044–1054CrossRefPubMedPubMedCentral Farrell B, Godwin J, Richards S, Warlow C (1991) The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 54:1044–1054CrossRefPubMedPubMedCentral
go back to reference Fitzmaurice C et al (2017) Global Regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015 a systematic analysis for the global burden of disease study. JAMA Oncol. 98121(4):524–548 Fitzmaurice C et al (2017) Global Regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015 a systematic analysis for the global burden of disease study. JAMA Oncol. 98121(4):524–548
go back to reference Ilbawi AM, Anderson BO (2015) Cancer in global health: how do prevention and early detection strategies relate? Global Health. 7(278):1–6 Ilbawi AM, Anderson BO (2015) Cancer in global health: how do prevention and early detection strategies relate? Global Health. 7(278):1–6
go back to reference Juul-Möller S, Edvardsson N, Jahnmatz B et al (1992) Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) group. Lancet 340:1421–1425CrossRefPubMed Juul-Möller S, Edvardsson N, Jahnmatz B et al (1992) Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) group. Lancet 340:1421–1425CrossRefPubMed
go back to reference Ma X, Yu H (2006) Global burden of cancer. Yale J Biol Med 79:85–94 Ma X, Yu H (2006) Global burden of cancer. Yale J Biol Med 79:85–94
go back to reference McNeil JJ, Nelson MR, Woods RL, Lockery JE et al (2018) Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 379(16):1519–1528CrossRefPubMedPubMedCentral McNeil JJ, Nelson MR, Woods RL, Lockery JE et al (2018) Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 379(16):1519–1528CrossRefPubMedPubMedCentral
go back to reference Medical Research Council's General Practice Research Framework (1998) Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet 351:233–241CrossRef Medical Research Council's General Practice Research Framework (1998) Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet 351:233–241CrossRef
go back to reference Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1–9CrossRefPubMedPubMedCentral Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1–9CrossRefPubMedPubMedCentral
go back to reference Ogawa H, Nakayama M, Morimoto T et al (2008) Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 300:2134–2142CrossRefPubMed Ogawa H, Nakayama M, Morimoto T et al (2008) Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 300:2134–2142CrossRefPubMed
go back to reference Okada S, Morimoto T, Ogawa H, Sakuma M et al (2018) Effect of aspirin on cancer chemoprevention in japanese patients with type 2 diabetes : 10-year observational follow-up of a randomized controlled trial. Diabetes Care. 41:1757–1764CrossRefPubMed Okada S, Morimoto T, Ogawa H, Sakuma M et al (2018) Effect of aspirin on cancer chemoprevention in japanese patients with type 2 diabetes : 10-year observational follow-up of a randomized controlled trial. Diabetes Care. 41:1757–1764CrossRefPubMed
go back to reference Rothwell PM, Fowkes FGR, Belch JFF, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. The Lancet 377(9759):31–41CrossRef Rothwell PM, Fowkes FGR, Belch JFF, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. The Lancet 377(9759):31–41CrossRef
go back to reference Seshasai SRK, Wijesuriya S, Sivakumaran R, Nethercott S, Erqou S, Sattar N, Ray KK (2012) Effect of aspirin on vascular and nonvascular outcomes. Arch Intern Med. 172(3):209–216CrossRefPubMed Seshasai SRK, Wijesuriya S, Sivakumaran R, Nethercott S, Erqou S, Sattar N, Ray KK (2012) Effect of aspirin on vascular and nonvascular outcomes. Arch Intern Med. 172(3):209–216CrossRefPubMed
go back to reference Stegeman I, Bossuyt PM, Yu T, Boyd C, Puhan MA (2015) Aspirin for primary prevention of cardiovascular disease and cancer, a benefit and harm analysis. Plos One. 2:1–12 Stegeman I, Bossuyt PM, Yu T, Boyd C, Puhan MA (2015) Aspirin for primary prevention of cardiovascular disease and cancer, a benefit and harm analysis. Plos One. 2:1–12
go back to reference The ASCEND study collaborative group (2018) Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 379(16):1529–1539CrossRef The ASCEND study collaborative group (2018) Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 379(16):1529–1539CrossRef
go back to reference The DAMAD Study Group (1989) Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. Diabetes 38:491–498CrossRef The DAMAD Study Group (1989) Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. Diabetes 38:491–498CrossRef
go back to reference The Persantine-Aspirin Reinfarction Study Research Group (1980) Persantine and aspirin in coronary heart disease. Circulation 62:449–461CrossRef The Persantine-Aspirin Reinfarction Study Research Group (1980) Persantine and aspirin in coronary heart disease. Circulation 62:449–461CrossRef
go back to reference The SALT Collaborative Group (1991) Swedish aspirin low-dose trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. Lancet 338:1345–1349CrossRef The SALT Collaborative Group (1991) Swedish aspirin low-dose trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. Lancet 338:1345–1349CrossRef
go back to reference Tsoi KKF et al (2019) Long-term use of low-dose aspirin for cancer prevention : a 10-year population cohort study in Hong Kong. Int J Cancer Tsoi KKF et al (2019) Long-term use of low-dose aspirin for cancer prevention : a 10-year population cohort study in Hong Kong. Int J Cancer
go back to reference Vane JR, Meade TW (1997) Second European Stroke Prevention Study (ESPS 2): clinical and pharmacological implications. J Neurol Sci 145(2):123–125PubMed Vane JR, Meade TW (1997) Second European Stroke Prevention Study (ESPS 2): clinical and pharmacological implications. J Neurol Sci 145(2):123–125PubMed
go back to reference Whitlock EP, Williams SB, Burda BU, Feightner A, Beil T (2015) Aspirin use in adults: cancer, all-cause mortality, and harms. A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 132. AHRQ Publication No. 13-05193-EF-1. Rockville, MD: Agency for Healthcare Research and Quality Whitlock EP, Williams SB, Burda BU, Feightner A, Beil T (2015) Aspirin use in adults: cancer, all-cause mortality, and harms. A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 132. AHRQ Publication No. 13-05193-EF-1. Rockville, MD: Agency for Healthcare Research and Quality
Metadata
Title
Safety and efficacy of aspirin for primary prevention of cancer: a meta-analysis of randomized controlled trials
Authors
Tarek Haykal
Mahmoud Barbarawi
Yazan Zayed
Anitha Yelangi
Harsukh Dhillon
Sowmya Goranta
Babikir Kheiri
Adam Chahine
Varun Samji
Josiane Kerbage
Khalil Katato
Ghassan Bachuwa
Publication date
01-07-2019
Publisher
Springer Berlin Heidelberg
Keyword
Warfarin
Published in
Journal of Cancer Research and Clinical Oncology / Issue 7/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02932-0

Other articles of this Issue 7/2019

Journal of Cancer Research and Clinical Oncology 7/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.