Aspirin in Primary Prevention of Stroke-Review of Evidence Through the Needs of Indian Clinical Settings
Introduction: Stroke Burden and Aspirin's Role
The stroke burden in India is substantial and growing, with an incidence of 119-145 per 100,000 annually (~0.12–0.15%). Importantly, 20–30% of strokes occur in individuals under 50, (1) substantially younger than the 70–75 years typically reported in Western populations. (2) Ischemic stroke is the most common subtype across all Population-Based Stroke Registries (PBSRs) in India, accounting for approximately 60% to 85% of all stroke cases. (3)
Stroke remains a leading cause of death and DALYs in India, highlighting the urgent need for effective primary prevention strategies. (1) Aspirin, with its well-established antiplatelet efficacy, continues to be widely considered for reducing the risk of first atherothrombotic (ischemic) stroke in at-risk individuals. (4)
Aspirin in Atherothrombotic Stroke: Evidence Review
Multiple large-scale studies have evaluated the role of aspirin in the primary prevention of stroke among at-risk populations. The ASCEND trial (A Study of Cardiovascular Events in Diabetes), a randomized, placebo-controlled trial involving 15,480 patients with diabetes but no prior CVD. Over a mean follow-up of 7.4 years, aspirin use was associated with a significant 12% relative reduction in serious vascular events, including ischemic stroke [HR: 0.88; 95% CI: 0.79–0.97; p = 0.01]. (5)
A recent meta-analysis of 11 randomized controlled trials, including both men and women without prior cardiovascular events, found a significant reduction in overall stroke risk in women using aspirin (OR 0.85; 95% CI: 0.73–0.99; p = 0.03), driven primarily by a 24% reduction in ischemic stroke [OR 0.76; 95% CI: 0.63–0.93; p = 0.008]. (6)
A comprehensive meta-analysis by the Antithrombotic Trialists’ Collaboration, including over 135,000 high-risk patients, demonstrated that aspirin reduced the risk of non-fatal stroke by approximately 25% compared to control. Among patients with prior stroke or transient ischemic attack, aspirin use resulted in an absolute risk reduction of 36 per 1000 over two years. Low-dose aspirin (75–150 mg daily) was found to be as effective as higher doses for long-term stroke prevention. (7)
Aspirin in Primary ASCVD Prevention - Where Guidelines Stand?
Guideline | Target Population | Recommendation for CVD (Including Stroke) Prevention | Conditions |
DCRM 2.0 [2024] (8) | Adults aged 40–59 with ≥2 CV risk factors (e.g., high Lp(a), HT, T2DM, dyslipidemia) | Low-dose aspirin may be considered | India-aligned criteria; individualized decision based on bleeding risk |
USPSTF [2022] (9) | Adults aged 40–59 years with ≥10% 10-year ASCVD risk | Recommends initiating aspirin | If bleeding risk is not elevated |
ESC [2021] (10) | Individuals with hypertension, dyslipidemia, and F/H of early ASCVD | Low-dose aspirin may be considered | If overall CV risk is high (SCORE2 ≥5%) and bleeding risk is low |
ACC/AHA [2019] (10) | Adults aged 40–70 years at high ASCVD risk | Supports considering aspirin | Provided bleeding risk is low |
India-Specific Considerations: Stroke Risk Profile Is Different
The early onset of stroke in India is primarily driven by poorly controlled cardiometabolic factors—hypertension, diabetes, dyslipidemia—and compounded by genetic risks such as elevated lipoprotein(a) and the South Asian “thin-fat” phenotype, marked by high visceral adiposity despite normal BMI, thereby supporting the need for considering selective aspirin initiation in appropriately risk-stratified individuals. (3)
Nearly 76% of Indian T2DM cases are uncontrolled; (11) only 1 in 3 patients with hypertension are even diagnosed. (12) In such a landscape, primary prevention tools like aspirin deserve contextual application, particularly in patients with overlapping CV risks.
Clinical Application: A Case-Based Insight into Stroke Prevention
Decision-support tools like AspirinGuide can aid clinicians in balancing benefits and bleeding risks in such high-risk individuals.
Key Takeaways
- Aspirin remains a clinically relevant option for the primary prevention of ischemic stroke in appropriately selected high-risk individuals, in Indian clinical settings.
- With India’s younger stroke onset, high burden of uncontrolled T2DM, hypertension, and genetic predispositions like elevated Lp(a), personalized risk-benefit assessment is critical.
- Guideline-aligned, context-specific use, supported by tools like AspirinGuide, can help clinicians optimize prevention while minimizing bleeding risks.
Reference:
1. Behera, D.K., Rahut, D.B. & Mishra, S. Analyzing stroke burden and risk factors in India using data from the Global Burden of Disease Study. Sci Rep 14, 22640 (2024). https://doi.org/10.1038/s41598-024-72551-4
2. Donkor ES. Stroke in the 21st Century: A Snapshot of the Burden, Epidemiology, and Quality of Life. Stroke Res Treat. 2018;2018:3238165. Published 2018 Nov 27. doi:10.1155/2018/3238165
3. Rangamani, Sukanya et al. “Stroke incidence, mortality, subtypes in rural and urban populations in five geographic areas of India (2018-2019): results from the National Stroke Registry Programme.” The Lancet regional health. Southeast Asia vol. 23 100308. 28 Oct. 2023, doi:10.1016/j.lansea.2023.100308
4. Hussain, Masaraf, et al. "Antiplatelet Effect of Aspirin in Ischemic Stroke: A Hospital-based Study." Journal of Advances in Medicine and Medical Research, vol. 33, no. 22, 2021, pp. 237–244. Article no. JAMMR.76481.
5. ASCEND Study Collaborative Group et al. “Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus.” The New England journal of medicine vol. 379,16 (2018): 1529-1539. doi:10.1056/NEJMoa1804988
6. Gdovinova, Zuzana et al. “Aspirin for Primary Stroke Prevention; Evidence for a Differential Effect in Men and Women.” Frontiers in neurology vol. 13 856239. 21 Jun. 2022, doi:10.3389/fneur.2022.856239
7. 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 (Clinical research ed.) vol. 324,7329 (2002): 71-86. doi:10.1136/bmj.324.7329.71
8. 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
9. Della Bona, Roberta, et al. "Aspirin in Primary Prevention: Looking for Those Who Enjoy It." Journal of Clinical Medicine, vol. 13, no. 14, 2024, article 4148, https://doi.org/10.3390/jcm13144148. Accessed 31 May 2025.
10. 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
11. Ismail IM, Naik PR. Prevalence and Determinants of Uncontrolled Diabetes Mellitus: A Community-Based Study from Karnataka, India. Natl J Community Med. 2024;15(10):842–849. doi:10.55489/njcm.151020244459
12. Varghese, Jithin Sam et al. “Hypertension Diagnosis, Treatment, and Control in India.” JAMA network open vol. 6,10 e2339098. 2 Oct. 2023, doi:10.1001/jamanetworkopen.2023.39098
Abbreviations: DALYs – Disability-Adjusted Life Years, PBSR – Population-Based Stroke Registry, ASCEND – A Study of Cardiovascular Events in Diabetes, CVD – Cardiovascular Disease, HR – Hazard Ratio, CI – Confidence Interval, OR – Odds Ratio, DCRM – Diabetes, Cardiorenal, and Metabolic Diseases, Lp(a) – Lipoprotein(a), HT – Hypertension, T2DM – Type 2 Diabetes Mellitus, CV – Cardiovascular, USPSTF – United States Preventive Services Task Force, ASCVD – Atherosclerotic Cardiovascular Disease, ESC – European Society of Cardiology, F/H – Family History, ACC/AHA – American College of Cardiology / American Heart Association, SCORE2 – Systematic Coronary Risk Estimation 2, BMI – Body Mass Index, E/O – Either/Or
