Aspirin in primary prevention of cardiovascular diseases: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Tingting ¹ , NIE Zhichao ¹ , TIAN Tian ¹ , LI Ailing ¹ ,  JIA Hong ^1,2

1. School of Public Health, Southwest Medical University, Luzhou, 646000, P.R.China;
2. Key Laboratory of Medical Electrophysidogy of Ministry of Education, Institute of Cardiovascular Research of Southwest Medical University, Collaborative Innovation Center for Prevention of Cardiovascular Disease, Luzhou, 646000, P.R.China;

Corresponding author：

JIA Hong, Email: jhong_lz@163.com

Keywords：

Aspirin; Cardiovascular disease; Primary prevention; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.201903057

Video：

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Objectives To systematically review the safety and efficacy of aspirin in primary prevention of cardiovascular diseases.Methods PubMed, EMbase, Web of Science, The Cochrane Library, CBM, WanFang Data, CNKI and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of aspirin for primary prevention of cardiovascular diseases from inception to November 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, and then, meta-analysis was performed by RevMan 5.3 software.Results A total of 13 RCTs involving 164 225 participants were included. The results of meta-analysis showed that: aspirin reduced the risk of myocardial infarction (RR=0.85, 95%CI 0.75 to 0.97, P=0.01), ischemic stroke (RR=0.86, 95%CI 0.79 to 0.95, P=0.002) and risk of major adverse cardiovascular events (RR=0.90, 95%CI 0.86 to 0.94, P<0.000 1). However, all-cause mortality (RR=0.97, 95%CI 0.93 to 1.02, P=0.22) and cardiovascular mortality (RR=0.93, 95%CI 0.85 to 1.02, P=0.11) were not reduced. Additionally, it increased risk of hemorrhagic stroke (RR=1.29, 95%CI 1.02 to 1.64, P=0.03), major bleeding (RR=1.43, 95%CI 1.31 to 1.56, P<0.000 01) and gastrointestinal bleeding (RR=1.59, 95%CI 1.33 to 1.90, P<0.000 01).Conclusion Current evidence shows that aspirin can reduce the incidence of major adverse cardiovascular events and myocardial infarction during primary prevention of cardiovascular disease, while increase the risk of bleeding, especially gastrointestinal bleeding. Therefore, its potential benefits may be offset. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusion.

Citation： LI Tingting, NIE Zhichao, TIAN Tian, LI Ailing, JIA Hong. Aspirin in primary prevention of cardiovascular diseases: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2019, 19(10): 1187-1194. doi: 10.7507/1672-2531.201903057 Copy

1.	陈伟伟, 高润霖, 刘力生, 等. 《中国心血管病报告 2017》概要. 中国循环杂志, 2018, 33(1): 1-8.
2.	Ezzati M, Hoorn SV, Rodgers A, et al. Estimates of global and regional potential health gains from reducing multiple major risk factors. Lancet, 2003, 362(9380): 271-280.
3.	廖玉华. 心血管疾病一级预防中阿司匹林作用机制的研究进展. 中华内科杂志, 2013, 52(10): 878-879.
4.	Steering committee of the physicians' health study research group. Final report on the aspirin component of the ongoing physicians' health study. N Engl J Med, 1989, 321(3): 129-135.
5.	Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke, 2011, 42(1): 227-276.
6.	Bibbins-Domingo K. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: us preventive services task force recommendation statement. Ann Intern Med, 2016, 164(12): 836-845.
7.	McCarthy M. FDA questions use of aspirin for primary prevention of stroke and heart attack. BMJ, 2014, 348: g3168.
8.	ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med, 2018, 379(16): 1529-1539.
9.	Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet, 2018, 392(10152): 1036-1046.
10.	Hayden M, Pignone M, Phillips C, et al. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med, 2002, 136(2): 161-172.
11.	Eidelman RS, Hebert PR, Weisman SM, et al. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med, 2003, 163(17): 2006-2010.
12.	Berger JS, Roncaglioni MC, Avanzini F, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA, 2006, 295(3): 306-313.
13.	Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed), 1988, 296(6618): 313-316.
14.	The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet, 1998, 351(9098): 233-241.
15.	Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet, 1998, 351(9118): 1755-1762.
16.	Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet, 2001, 357(9250): 89-95.
17.	Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med, 2005, 352(13): 1293-1304.
18.	Belch J, MacCuish A, Campbell I, et al. 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, 2008, 337: a1840.
19.	Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA, 2008, 300(18): 2134-2141.
20.	Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA, 2010, 303(9): 841-848.
21.	Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA, 2014, 312(23): 2510-2520.
22.	McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med, 2018, 379(16): 1509-1518.
23.	McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med, 2018, 379(16): 1519-1528.
24.	McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med, 2018, 379(16): 1499-1508.
25.	Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet, 2009, 373(9678): 1849-1860.
26.	Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. Am J Cardiol, 2011, 107(12): 1796-1801.
27.	Raju N, Sobieraj-Teague M, Hirsh J, et al. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med, 2011, 124(7): 621-629.
28.	Seshasai SR, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med, 2012, 172(3): 209-216.
29.	Sutcliffe P, Connock M, Gurung T, et al. Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. PLoS One, 2013, 8(12): e81970.
30.	Ueshima H, Sekikawa A, Miura K, et al. Cardiovascular disease and risk factors in Asia: a selected review. Circulation, 2008, 118(25): 2702-2709.
31.	ASPREE Investigator Group. Study design of aspirin in reducing events in the elderly (ASPREE): a randomized, controlled trial. Contemp Clin Trials, 2013, 36(2): 555-564.
32.	Chin AL, Negash S, Hamilton R. Diversity and disparity in dementia: the impact of ethnoracial differences in Alzheimer disease. Alzheimer Dis Assoc Disord, 2011, 25(3): 187-195.
33.	Carnethon MR, Pu J, Howard G, et al. Cardiovascular health in african americans: a scientific statement from the American Heart Association. Circulation, 2017, 136(21): e393-e423.
34.	Eskandarian R, Razavi M, Fattah A, et al. Prevalence of aspirin resistance in patients with type II diabetes: a descriptive-analytical study? Int J Clin Pharmacol Ther, 2017, 55(6): 493-497.
35.	Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ, 2002, 324(7329): 71-86.
36.	Patrono C. The multifaceted clinical readouts of platelet inhibition by low-dose aspirin. J Am Coll Cardiol, 2015, 66(1): 74-85.
37.	D'Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the framingham heart study. Circulation, 2008, 117(6): 743-753.
38.	Conroy RM, Pyörälä K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J, 2003, 24(11): 987-1003.
39.	Hippisley-Cox J, Coupland C, Vinogradova Y, et al. Derivation and validation of QRISK, a new cardiovascular disease risk score for the United Kingdom: prospective open cohort study. BMJ, 2007, 335(7611): 136.
40.	Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines. Circulation, 2014, 129(25 Suppl 2): S49-S73.
41.	Yang X, Li J, Hu D, et al. Predicting the 10-year risks of atherosclerotic cardiovascular disease in Chinese population: the China-PAR project (prediction for ASCVD risk in China). Circulation, 2016, 134(19): 1430-1440.
42.	Nagy P, Johansson S, Molloy-Bland M. Systematic review of time trends in the prevalence of Helicobacter pylori infection in China and the USA. Gut Pathog, 2016, 8: 8.
43.	Rothwell PM, Cook NR, Gaziano JM, et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet, 2018, 392(10145): 387-399.

1. 陈伟伟, 高润霖, 刘力生, 等. 《中国心血管病报告 2017》概要. 中国循环杂志, 2018, 33(1): 1-8.
2. Ezzati M, Hoorn SV, Rodgers A, et al. Estimates of global and regional potential health gains from reducing multiple major risk factors. Lancet, 2003, 362(9380): 271-280.
3. 廖玉华. 心血管疾病一级预防中阿司匹林作用机制的研究进展. 中华内科杂志, 2013, 52(10): 878-879.
4. Steering committee of the physicians' health study research group. Final report on the aspirin component of the ongoing physicians' health study. N Engl J Med, 1989, 321(3): 129-135.
5. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke, 2011, 42(1): 227-276.
6. Bibbins-Domingo K. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: us preventive services task force recommendation statement. Ann Intern Med, 2016, 164(12): 836-845.
7. McCarthy M. FDA questions use of aspirin for primary prevention of stroke and heart attack. BMJ, 2014, 348: g3168.
8. ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med, 2018, 379(16): 1529-1539.
9. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet, 2018, 392(10152): 1036-1046.
10. Hayden M, Pignone M, Phillips C, et al. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med, 2002, 136(2): 161-172.
11. Eidelman RS, Hebert PR, Weisman SM, et al. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med, 2003, 163(17): 2006-2010.
12. Berger JS, Roncaglioni MC, Avanzini F, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA, 2006, 295(3): 306-313.
13. Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed), 1988, 296(6618): 313-316.
14. The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet, 1998, 351(9098): 233-241.
15. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. Lancet, 1998, 351(9118): 1755-1762.
16. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet, 2001, 357(9250): 89-95.
17. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med, 2005, 352(13): 1293-1304.
18. Belch J, MacCuish A, Campbell I, et al. 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, 2008, 337: a1840.
19. Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA, 2008, 300(18): 2134-2141.
20. Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA, 2010, 303(9): 841-848.
21. Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA, 2014, 312(23): 2510-2520.
22. McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med, 2018, 379(16): 1509-1518.
23. McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med, 2018, 379(16): 1519-1528.
24. McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med, 2018, 379(16): 1499-1508.
25. Antithrombotic Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet, 2009, 373(9678): 1849-1860.
26. Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. Am J Cardiol, 2011, 107(12): 1796-1801.
27. Raju N, Sobieraj-Teague M, Hirsh J, et al. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med, 2011, 124(7): 621-629.
28. Seshasai SR, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med, 2012, 172(3): 209-216.
29. Sutcliffe P, Connock M, Gurung T, et al. Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials. PLoS One, 2013, 8(12): e81970.
30. Ueshima H, Sekikawa A, Miura K, et al. Cardiovascular disease and risk factors in Asia: a selected review. Circulation, 2008, 118(25): 2702-2709.
31. ASPREE Investigator Group. Study design of aspirin in reducing events in the elderly (ASPREE): a randomized, controlled trial. Contemp Clin Trials, 2013, 36(2): 555-564.
32. Chin AL, Negash S, Hamilton R. Diversity and disparity in dementia: the impact of ethnoracial differences in Alzheimer disease. Alzheimer Dis Assoc Disord, 2011, 25(3): 187-195.
33. Carnethon MR, Pu J, Howard G, et al. Cardiovascular health in african americans: a scientific statement from the American Heart Association. Circulation, 2017, 136(21): e393-e423.
34. Eskandarian R, Razavi M, Fattah A, et al. Prevalence of aspirin resistance in patients with type II diabetes: a descriptive-analytical study? Int J Clin Pharmacol Ther, 2017, 55(6): 493-497.
35. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ, 2002, 324(7329): 71-86.
36. Patrono C. The multifaceted clinical readouts of platelet inhibition by low-dose aspirin. J Am Coll Cardiol, 2015, 66(1): 74-85.
37. D'Agostino RB Sr, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the framingham heart study. Circulation, 2008, 117(6): 743-753.
38. Conroy RM, Pyörälä K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J, 2003, 24(11): 987-1003.
39. Hippisley-Cox J, Coupland C, Vinogradova Y, et al. Derivation and validation of QRISK, a new cardiovascular disease risk score for the United Kingdom: prospective open cohort study. BMJ, 2007, 335(7611): 136.
40. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines. Circulation, 2014, 129(25 Suppl 2): S49-S73.
41. Yang X, Li J, Hu D, et al. Predicting the 10-year risks of atherosclerotic cardiovascular disease in Chinese population: the China-PAR project (prediction for ASCVD risk in China). Circulation, 2016, 134(19): 1430-1440.
42. Nagy P, Johansson S, Molloy-Bland M. Systematic review of time trends in the prevalence of Helicobacter pylori infection in China and the USA. Gut Pathog, 2016, 8: 8.
43. Rothwell PM, Cook NR, Gaziano JM, et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet, 2018, 392(10145): 387-399.

Chinese Journal of Evidence-Based Medicine

Aspirin in primary prevention of cardiovascular diseases: a meta-analysis

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