Aspirin in Primary Prevention- When to Consider?

Reframing Aspirin's Role in Primary Prevention: Evolving evidence has refined our understanding of aspirin's role in primary prevention. While earlier trials established cardiovascular benefits, more recent data emphasize the importance of patient selection to optimise outcomes. A 2019 meta-analysis (N=164,225) showed aspirin reduced serious vascular events by 12% and non-fatal MI by ~20%, with a manageable rise in major bleeding [HR 1.43; NNH 210] (1); the Antithrombotic Trialists’ Collaboration echoed that absolute benefits in primary prevention, though smaller than in secondary prevention, remain clinically relevant in high-risk individuals, especially those with diabetes or multiple cardiovascular risk factors. (2)

This evolution is reflected in current guidelines. The USPSTF (United States Preventive Services Task Force, 2022) recommends individualized use of aspirin in adults aged 40–59 years with a ≥10% 10-year CVD risk. The ESC (European Society of Cardiology, 2021) suggests aspirin for patients with diabetes who are at high or very high cardiovascular risk and have no contraindications. The ACC/AHA (American College of Cardiology/American Heart Association, 2019) supports aspirin use in adults aged 40–70 years who are at high ASCVD risk and have a low risk of bleeding. Together, these guidelines support a risk-based approach, where judicious aspirin use offers preventive value in selected individuals. (3)

India’s Premature CVD Burden Requires a Different Lens: Indians develop CVD nearly a decade earlier than Western populations, with the age of developing MI being 53 years in Indians compared to 58 years in Western countries. (4) Premature deaths account for 62% of CVD mortality, and one-third of acute coronary syndrome cases occur before age 50. Despite this burden, less than half of patients with hypertension and diabetes are treated, and only ~20% achieve control. (5) Conventional 10-year risk scores often underestimate risk in younger Indians, making lifetime risk tools likely more appropriate. Genetic predisposition, inflammatory states, thin-fat phenotype, and poor cardiometabolic risk factor control heighten ASCVD risk, supporting earlier, more aggressive prevention, including aspirin when indicated. (4)

Lifetime Risk Depends on Classic Modifiable Factors: A pooled analysis by the Global Cardiovascular Risk Consortium (2025) highlighted the long-term impact of five key risk factors—cardio-metabolic (hypertension, diabetes, dyslipidemia), partially modifiable (smoking), and metabolic lifestyle-related (abnormal BMI)—which together account for ~50% of global CVD burden. At age 50, individuals with all five had a lifetime CVD risk of 38% in men and 24% in women, while those without gained 10–13 additional CVD-free years. Midlife modification of blood pressure and smoking provided the greatest gains in both CVD-free and overall survival, indicating the importance of early, integrated risk factor control for primary prevention. (6) In India, control of cardio-metabolic risk is poor, with only ~7% of T2D patients meeting targets for glucose, BP, and lipids, (7) and over 50% of newly diagnosed cases are overweight or obese, highlighting the need for aggressive CVD prevention. (8)

Individualized Use: CV Risk, Age, and Bleeding Must Guide: In primary prevention, the net clinical benefit of aspirin lies in carefully balancing ischemic versus bleeding risk. Risk scores often overlook enhancers such as kidney disease, family history, elevated Lp(a), or low socioeconomic status. (3) In individuals with elevated Lp(a ≥50 mg/dL), aspirin was linked to a 52% lower risk of ASCVD mortality (HR 0.48), supporting a precision-guided approach. For high-risk patients with low bleeding risk, accurate risk stratification is key to identifying when aspirin adds true preventive value with minimal harm. Clinical tools such as the Aspirin-Guide app support personalised decision-making for initiating aspirin for CV event prevention. (9)

Case Profile: High-Risk, Low-Bleed– A Candidate for Aspirin: A 55-year-old hypertensive, sedentary male with a family history of premature CHD. BMI: 26 kg/m²; systolic BP: 150 mmHg; total cholesterol: 220 mg/dL; HDL: 40 mg/dL. He is a non-smoker, non-diabetic, with no history of GI bleeding, peptic ulcer disease, or NSAID/steroid use.

His profile includes cardio-metabolic risk factors (hypertension, elevated LDL-C), a non-modifiable risk (family history of ASCVD), and a metabolic lifestyle-linked factor (BMI). He qualifies as high CV risk with low bleeding risk, where aspirin offers likely net benefit, per DCRM 2.0 (Diabetes, Cardiorenal, and Metabolic Diseases) 2024 guidelines recommending low-dose aspirin (75–100 mg/day) in such patients with ≥2 major risk factors.

Final Message: Low-dose aspirin for primary prevention is appropriate in individuals with elevated ASCVD risk and low bleeding risk. Current guidelines and risk assessment tools support a selective, individualised approach. When initiated in the right patient profile, aspirin can help reduce the incidence of primary cardiovascular events.

References:

1. Zheng, Sean L, and Alistair J Roddick. “Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis.” JAMA vol. 321,3 (2019): 277-287. doi:10.1001/jama.2018.20578

2. Antithrombotic Trialists' (ATT) Collaboration et al. “Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.” Lancet (London, England) vol. 373,9678 (2009): 1849-60. doi:10.1016/S0140-6736(09)60503-1

3. Della Bona, Roberta et al. “Aspirin in Primary Prevention: Looking for Those Who Enjoy It.” Journal of clinical medicine vol. 13,14 4148. 16 Jul. 2024, doi:10.3390/jcm13144148

4. Puri, Raman et al. “Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.” Journal of clinical lipidology vol. 18,3 (2024): e351-e373. doi:10.1016/j.jacl.2024.01.006

5. 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

6. Global Cardiovascular Risk Consortium et al. “Global Effect of Cardiovascular Risk Factors on Lifetime Estimates.” The New England journal of medicine, 10.1056/NEJMoa2415879. 30 Mar. 2025, doi:10.1056/NEJMoa2415879

7. Anjana, Ranjit Mohan et al. “Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).” The lancet. Diabetes & endocrinology vol. 11,7 (2023): 474-489. doi:10.1016/S2213-8587(23)00119-5

8. Dalal, N., Patel, D., Chaturvedi, A., & Shah, A. (2022). Real-world observational study to capture demographic details of newly diagnosed type 2 diabetes mellitus. International Journal of Research in Medical Sciences, 10(10), 2251–2256. https://doi.org/10.18203/2320-6012.ijrms20222375

9. Razavi, Alexander C et al. “Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).” American journal of preventive cardiology vol. 18 100674. 27 Apr. 2024, doi:10.1016/j.ajpc.2024.100674

10. 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