Indian CV Risk Factors and Emerging Evidence for Aspirin in Primary Prevention- What's New?

Cardiovascular diseases (CVDs) remain the leading cause of mortality and disability in India, contributing to 31.8% of deaths. Noncommunicable diseases (NCDs), including CVDs, account for 60% of all deaths. India’s age-standardized death rate for CVDs (282 per 100,000) surpasses the global average (233 per 100,000), highlighting the country’s high disease burden. Major risk factors such as hypertension, diabetes, high cholesterol, obesity, sedentary lifestyle, and poor diet continue to drive such disheartening CV risk trends. (1) Approximately 25% of the Indian population also have elevated lipoprotein(a) [Lp(a)] levels (≥50 mg/dL), indicating Lp(a) as a significant cardiovascular risk factor. (2) Given this high cardio-metabolic risk context, emerging evidence on aspirin for primary prevention becomes crucial in mitigating India's rising cardiovascular risk.

How does Indian CV Risk Differ from Western Populations?

India’s CVD burden is distinct from that of Western nations. In India, 52% of CVD deaths occur before 70 years, compared to just 23% in Western countries. (3)  It is noteworthy that younger individuals tend to have an overall lower bleeding risk. (4)

Case fatality due to CVD is also higher in low-income nations, including India, than in middle- and high-income countries. Indians develop CVD at least a decade earlier than Europeans, often during their most productive midlife years, making the impact more severe. (3) Only 7% of Indian patients with diabetes have controlled HbA1c, blood pressure, and cholesterol, indicating poor CV risk factor control. (5)

Why Global Aspirin Primary Prevention Trials May Not Apply to India?

Most large-scale aspirin trials for cardiovascular prevention have not significantly included Indian patients. This makes it uncertain whether their findings fully apply to the Indian population, particularly in evaluating the risk-benefit balance of aspirin therapy for primary prevention in at-risk individuals.

Effective ACS prevention strategies have reduced event rates in developed countries, limiting aspirin's primary prevention benefit. However, in India, these measures are not widely implemented, suggesting aspirin may still have a role. Real-world evidence (RWE) trials including Indian patients could reveal a lower threshold for its effectiveness, making it a valuable option rather than completely dismissing it based on global studies. (4)

Aspirin in Primary Prevention: Spotlight on Evidence: The Antithrombotic Trialists’ (ATT) meta-analysis of six major primary prevention trials (95,000 patients) found a 12% relative reduction in cardiovascular events (0.51% vs. 0.57% per year, p=0.0001), mainly due to a significant decrease in nonfatal myocardial infarctions (0.18% vs. 0.23% per year, p<0.0001). The study demonstrated aspirin’s potential in reducing heart attacks in primary prevention. (6)

Recent studies suggest that individuals with elevated Lipoprotein(a) [Lp(a)] may benefit more from low-dose aspirin due to its role in atherothrombosis. Those with Lp(a) ≥50 mg/dL and carriers of the rs3798220-C polymorphism in the LPA gene have shown a greater reduction in coronary heart disease risk with aspirin use. (7)

Aspirin in Primary Prevention – Individualise:

Aspirin’s role in primary CVD prevention is increasingly personalized, with guidelines advocating for an individualized approach. The USPSTF(United States Preventive Services Task Force) recommends considering low-dose aspirin for adults aged 40–59 years with ≥10% 10-year CVD risk, while ACC/AHA (American College of Cardiology/American Heart Association)suggests it for adults aged 40–70 years at higher CVD risk but not at increased bleeding risk. The ESC (European Society of Cardiology) highlights aspirin’s potential for very high-risk individuals. (8) As personalized risk assessment becomes key, tools like the Aspirin-Guide app assist clinicians in identifying appropriate candidates for aspirin use.

Case Profile: When to Consider Aspirin in Primary Prevention:

For example, a 55-year-old man with hypertension, depression, sedentary lifestyle, and a family history of premature CHD presents a case where aspirin for primary prevention warrants careful consideration. Given his multiple risk factors, aspirin may potentially help reduce myocardial infarction risk. Following USPSTF recommendations, his CHD risk assessment should guide the decision, ensuring a balance between cardiovascular benefits and bleeding risk. If his five-year CHD risk is at least 3–5%, low-dose aspirin (75–81 mg daily) could be considered, with regular monitoring for adverse effects. (9)

Final Message

CVD remains a major health challenge in India, with a high early mortality rate. Emerging evidence suggests aspirin’s role in primary prevention may be particularly relevant for high-risk individuals, including those with >2 ASCVD risk factors with low bleeding risk. Guidelines support a personalized approach, supported by risk assessment tools like the Aspirin-Guide app to help achieve the best patient care outcomes.

References:

1. Jan, Bisma et al. “Cardiovascular Diseases Among Indian Older Adults: A Comprehensive Review.” Cardiovascular therapeutics vol. 2024 6894693. 25 Jun. 2024, doi:10.1155/2024/6894693

2. Enas EA, Varkey B, Dharmarajan TS, Pare G, Bahl VK. Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians. Indian Heart J. 2019;71(3):184-198. doi:10.1016/j.ihj.2019.04.007

3. Prabhakaran, Dorairaj et al. “Cardiovascular Diseases in India: Current Epidemiology and Future Directions.” Circulation vol. 133,16 (2016): 1605-20. doi:10.1161/CIRCULATIONAHA.114.008729

4. Rao, B. Hygriv. "Aspirin for Primary Prevention—Unveiling a Historical Truth and Choosing the Right Patient." Journal of Clinical and Preventive Cardiology, vol. 1, no. 3-4, 2020, https://doi.org/10.1177/2632463620976273.

5. 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

6. 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

7. Sukkari, Mohamad Hekmat et al. “Is there a benefit of aspirin therapy for primary prevention to reduce the risk of atherosclerotic cardiovascular disease in patients with elevated Lipoprotein (a)-A review of the evidence.” American journal of preventive cardiology vol. 15 100579. 1 Sep. 2023, doi:10.1016/j.ajpc.2023.100579

8. Berger JS. Aspirin for Primary Prevention—Time to Rethink Our Approach. JAMA Netw Open. 2022;5(4):e2210144. doi:10.1001/jamanetworkopen.2022.10144

9. American Academy of Family Physicians. "Aspirin for the Primary Prevention of Cardiovascular Events." American Family Physician, 1 Nov. 2002, https://www.aafp.org/pubs/afp/issues/2002/1101/p1737.html.