Aspirin in Primary Prevention: Prudent Guideline-Based Approach

Aspirin in Primary Prevention: Need for Delineating High CV-Risk, Low-Bleeding-Risk Profiles: Aspirin in primary prevention requires a nuanced, risk-stratified approach to balance CV benefits with bleeding risks. (1) In India, where the cardiovascular disease (CVD) burden is significantly greater than in many Western countries; marked by elevated Lp(a) in 25% of the population, (2) higher CVD mortality rates, earlier disease onset, and more premature deaths, (3) aspirin may offer potential benefits for carefully selected individuals at high cardiovascular risk but with low bleeding propensity.

Guideline Recommendations of Aspirin – When to Consider? Several guidelines converge on a selective-use strategy based on individual risk assessment. Accurate CV risk assessment remains a key factor in guiding aspirin therapy. Low-dose aspirin (75–100 mg) may be considered for primary ASCVD prevention in high-risk adults aged 40 to 60 years without a significant bleeding risk. In diabetes with elevated cardiovascular risk, aspirin may be appropriate if the risk of bleeding is minimal. [ACC/AHA, USPSTF, ADA] (1,4,5,6) In regard to peripheral artery disease, the ESC guidelines suggest low-dose aspirin use in asymptomatic carotid artery stenosis of >50% at low bleeding risk.(1) In summary, identifying subgroups at heightened risk but with minimal bleeding risk is pivotal in determining the appropriate use of aspirin.

Recent updates further refine patient selection for aspirin therapy in the Indian context. The DCRM 2.0 2024 recommendations suggest considering aspirin therapy in individuals with two or more CV risk factors, including elevated LDL-C, non-HDL-C, Lp(a), low HDL-C, diabetes, hypertension, CKD, smoking, family history of ASCVD, or a CAC score >100. However, given the increased bleeding risk, careful assessment and ongoing monitoring are essential. (6)

Aspirin in Primary Prevention – When Not to Use?: Breaking A Clinical Dilemma

Equally important is the identification of scenarios where aspirin use may be inappropriate or harmful, aiming to delineate the optimal therapeutic applicability of aspirin in the primary prevention of CVD.

Case Exemplar 1: Lower CV Risk Profile

• Patient: 42-year-old male with controlled hypertension and no history of ASCVD.
• Risk Assessment: Despite controlled hypertension, the patient has no additional cardiovascular risk factors. The anticipated cardiovascular benefit of aspirin is minimal, while the potential risk of bleeding may remain a concern.
• Clinical Decision-Making: Given the low cardiovascular risk and the absence of multiple risk factors, aspirin may not be considered, and unnecessary bleeding risk could be avoided. Clinical evidence also indicated the limited net benefit of aspirin in low-risk populations with fewer than 2 CV risk factors. (7)
• Lesson Learned: In low CV-risk individuals, the protective benefit of aspirin is limited, and the bleeding risk may outweigh potential therapeutic gains.

Case Exemplar 2: Higher Bleeding Risk Profile

• Patient: 65-year-old male with controlled hypertension, elevated Lp(a), and a history of GI ulcer treated with PPI.
• Risk Assessment: Although the patient has elevated Lp(a), indicating a higher cardiovascular risk, the history of GI ulcer significantly increases the risk of bleeding, more so in elderly patient
• Clinical Decision-Making: Despite the potential cardiovascular benefit, the elevated bleeding risk, particularly from recurrent GI bleeding, outweighs the marginal cardiovascular reduction that aspirin might provide. Thus, aspirin was not recommended, and GI prophylaxis was continued.
• Lesson Learned: In patients with a prior history of significant bleeding, aspirin use in primary prevention may likely pose greater harm than benefit, regardless of cardiovascular risk factors.

To guide decision-making, clinicians must weigh these opposing risks using evidence-based frameworks.

Optimizing Risk Management: Tailoring Aspirin Use

Aspirin – When to Avoid?: Aspirin use is generally not recommended in the following scenarios: adults with increased bleeding risk [ACC/AHA] (4), individuals with heightened bleeding risk factors such as peptic ulcer disease, anticoagulant use, or thrombocytopenia [DCRM 2.0] (5), those with low or moderate CVD risk where the bleeding risk outweighs cardiovascular benefits [ESC] (6), diabetes with no major ASCVD risk factors [ADA] (8), and individuals 60 years or older for primary prevention of CVD [USPSTF]. (1)

Tools like AspirinGuide can assist clinicians in systematically assessing both CV and bleeding risks, facilitating a more targeted application of aspirin.

Final Message

• In India, where cardiovascular risk is substantial, the reluctance to use aspirin in primary prevention, when indicated, may lead to missed therapeutic opportunities.
• A targeted approach with aspirin use helps mitigate bleeding risks while ensuring that high-risk yet low-bleeding-risk patients receive appropriate cardiovascular protection.
• By clarifying when not to use aspirin, clinicians can effectively balance therapeutic gains with safety, optimizing primary prevention strategies in deserving cases.

Reference: 

1. Della Bona R, Giubilato S, Palmieri M, Benenati S, Rossini R, Di Fusco SA, Novarese F, Mascia G, Gasparetto N, Di Monaco A, et al. Aspirin in Primary Prevention: Looking for Those Who Enjoy It. Journal of Clinical Medicine. 2024; 13(14):4148. https://doi.org/10.3390/jcm13144148

2. Enas, Enas A et al. “Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians.” Indian heart journal vol. 71,3 (2019): 184-198. doi:10.1016/j.ihj.2019.04.007

3. Kalra, Ankur et al. “The burgeoning cardiovascular disease epidemic in Indians - perspectives on contextual factors and potential solutions.” The Lancet regional health. Southeast Asia vol. 12 100156. 10 Feb. 2023, doi:10.1016/j.lansea.2023.100156

4. Arnett, Donna K et al. “2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.” Journal of the American College of Cardiology vol. 74,10 (2019): 1376-1414. doi:10.1016/j.jacc.2019.03.009

5. Handelsman, Yehuda et al. “DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.” Metabolism: clinical and experimental vol. 159 (2024): 155931. doi:10.1016/j.metabol.2024.155931

6. Visseren, Frank L J et al. “2021 ESC Guidelines on cardiovascular disease prevention in clinical practice.” European heart journal vol. 42,34 (2021): 3227-3337. doi:10.1093/eurheartj/ehab484

7. Mahmoud, Ahmed N et al. “Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials.” European heart journal vol. 40,7 (2019): 607-617. doi:10.1093/eurheartj/ehy813

8. American Diabetes Association Professional Practice Committee . “10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2025.” Diabetes care vol. 48,Supplement_1 (2025): S207-S238. doi:10.2337/dc25-S010

Abbreviations: USPSTF; United States Preventive Services Task Force, MI; myocardial infarction, HR; hazard ratio, RR; relative risk, ESC; European Society of Cardiology, ACC/AHA; American College of Cardiology/ American Heart Association, ASCVD; atherosclerotic cardiovascular disease, T2D; type 2 diabetes, DCRM; Diabetes, Cardiorenal, and Metabolic Diseases.