Clinical Research StudyA Meta-Analysis of Aspirin for the Primary Prevention of Cardiovascular Diseases in the Context of Contemporary Preventive Strategies
Introduction
In patients with known cardiovascular diseases, aspirin is the cornerstone therapy based on robust evidence that it provides a net benefit in secondary prevention.1, 2 However, in primary prevention, its net balance between benefit and harm is unclear, given the most current evidence. Current guidelines also conflict, some recommending aspirin for primary prevention, and others not.1, 3, 4, 5 Individual randomized clinical trials (RCTs) have reached conflicting conclusions,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 but meta-analyses of those RCTs suggest that aspirin is effective in the primary prevention of cardiovascular diseases, a result predominantly driven by a small decrease in the risk of myocardial infarction.17, 18, 19 Prior meta-analyses have been criticized because they included older trials that enrolled patient populations with higher smoking rates and lower use of risk-modifying medications such as antihypertensive agents and statins.17, 20, 21
Since those trials, major advances have been made in cardiovascular diseases prevention strategies, including statins for primary prevention.22, 23, 24 Following some early RCTs supporting the use of statins for primary prevention,22, 23 the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) published clinical guidelines in 2001, recommending intensive cholesterol-lowering therapy in clinical practice.25 Those guidelines led to a significant increase in statin use among US adults as early as 2003, resulting in a substantive improvement in population low-density lipoprotein levels.26 Therefore, it is unclear whether aspirin is effective for primary prevention of cardiovascular events in contemporary clinical practice. Recent RCTs have investigated the current role of aspirin in primary prevention on the background of contemporary preventive strategies.27, 28, 29, 30 Therefore, an updated meta-analysis of RCTs was performed to evaluate the safety and efficacy of aspirin for the primary prevention of cardiovascular diseases. Additionally, a moderator analysis was performed using data from only those trials reported after the publication of the NCEP-ATP III guidelines to investigate the safety and efficacy of aspirin for primary prevention of cardiovascular disease in the context of contemporary preventive strategies.
Section snippets
Methods
This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses.31
Study Selection and Patient Population
Fourteen RCTs including 164,751 patients (48% male) satisfied the inclusion criteria.6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 27, 28, 29, 30 The search flow diagram is shown in Supplementary Figure 1 (Appendix, available online), and the bias assessment for each RCT is shown in Supplementary Figure 2 (Appendix, available online). The majority of these studies were high-quality trials based on Cochrane Collaboration guidelines (Supplementary Figure 2). Supplementary Table 1 (Appendix, available
Discussion
In this study of 164,751 patients enrolled in 14 RCTs, we compared the efficacy and safety of aspirin use for the primary prevention of cardiovascular diseases. We found that aspirin use in patients without known cardiovascular diseases decreased the risk of myocardial infarction by 16% at the expense of increased risks for major bleeding and hemorrhagic stroke (49% and 25%, respectively). The risks for all-cause stroke, cardiovascular mortality, and all-cause mortality were not affected.
Conclusions
Based on this meta-analysis, in patients without known cardiovascular diseases, aspirin decreases the risk of myocardial infarction by 16%, at the expense of increasing risks for major bleeding and hemorrhagic stroke (49% and 25%, respectively) without affecting the risks for all-cause stroke, all-cause mortality, or cardiovascular mortality. Furthermore, in contemporary practice, where statins and other measures are used aggressively for primary prevention, aspirin might not even decrease
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Cited by (15)
Implications of the heterogeneity between guideline recommendations for the use of low dose aspirin in primary prevention of cardiovascular disease
2022, American Journal of Preventive CardiologyShould Senior Citizens Take Aspirin Daily to Prevent Heart Attacks or Strokes?
2021, American Journal of MedicineDifferences in the prevention and control of cardiovascular and cerebrovascular diseases
2021, Pharmacological ResearchCitation Excerpt :Meta-analysis results on the primary prevention of CEVDs and CAVDs using aspirin in the last three years show that aspirin is associated with a lower risk of MI and an increased risk of major bleeding, but not with a reduction in the incidence of all-cause mortality [23,47,51–56] (Table 3). Most meta-analysis results suggest that aspirin is not associated with a reduction in stroke [47,51,53,55,56] (Table 3). However, none of the meta-analyses analyzed the role of aspirin in the primary prevention of total CEVDs and CAVDs separately.
Thrombotic, Vascular, and Bleeding Complications of the Myeloproliferative Neoplasms
2021, Hematology/Oncology Clinics of North AmericaCitation Excerpt :The ASCEND trial of 15,480 patients with diabetes mellitus to determine the effects of aspirin versus placebo on cardiovascular complications found a 12% decrease in serious cardiovascular events in the aspirin group, accompanied by a 29% increase in major bleeding problems (approximately 41% gastrointestinal, 21% intraocular, and 17% intracranial bleeds), with a median follow-up of 7.4 years.94 Subsequently published systematic reviews and meta-analyses concluded that, in contemporary practice, the routine use of aspirin for the primary prevention of cardiovascular events may have a net harmful effect.95–97 It is important to point out that all of these studies were designed for primary prevention (ie, persons with no past history of a thrombotic or vascular event), not for secondary prevention in patients with previous clinical events.
Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis
2020, American Journal of MedicineCitation Excerpt :However, when analyzing only newer trials (published since 2005), aspirin had no effect on the rate of ASCVD events compared with placebo. Both older and newer trials found increased rates of major bleeding among participants randomized to aspirin.23 In addition to including the HOT trial,22 this meta-analysis also included the Early Treatment Diabetic Retinopathy Study (ETDRS).
Funding: None.
Conflict of Interest: None.
Authorship: All listed authors have access to the data and substantially contributed to the conception and design, acquisition of data, and revising it critically for important intellectual content.