Theory to Practice: Implementing Aspirin and Statin Therapy in Primary Care Settings
Premature ASCVD in India
The prevalence of atherosclerotic cardiovascular disease (ASCVD) has been increasing in India, surpassing infectious diseases as the leading cause of death among Indians. Early onset and rapid progression of the disease further magnify its burden.1 In India, CVD incidence is reportedly 4.4 per 1,000 person-years, with a mortality rate of 8.4 per 1,000 person-years, and premature deaths make up 62% of all CVD deaths.2,3
Need for Aggressive Treatment Measures for ASCVD Prevention
The recent Lipid Association of India (LAI) report highlights that premature ASCVD is pervasive and threatening in India demanding the need for early institution of aggressive preventive measures to protect the young population prior to the development of ASCVD. 4Effective primary prevention relies on pharmacotherapy, with evidence and guidelines supporting the use of statins and aspirin.
Aspirin has been widely utilized for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statins have markedly improved cardiovascular outcomes and substantially enhanced cardiovascular outcomes.5,6 Many high-risk individuals under 50 years of age, who do not have a history of cardiovascular disease, are frequently underserved. Current research falls short in addressing the complexities of cardiovascular risk factors and their management in real-world settings.7 The LEADD study (n=4002) found that approximately 80% of patients with ASCVD or risk factors were not on the recommended statin dosage.8This highlights the urgent need for healthcare professionals to address these gaps and optimize early treatment for high-CV-risk patients.
Importance of Aspirin and Statin therapy in Primary Prevention:
For primary CVD prevention, aspirin reduces the risk of major vascular events by 15% to 20%. Statins lower cardiovascular event incidence by up to 40% through cholesterol reduction and plaque stabilization. Combining statins with aspirin may be more effective than aspirin alone.9
Evidence-Based Guidelines
A summary of current guidelines for statin and aspirin usage is presented in the following table.
Table 1
Guideline | Recommendation dose/intensity | Recommended Aged | Patient Risk level | ||
Aspirin | |||||
AHA10 | Low-dose i.e. 75-100 mg/dl | 40-55 years | Elevated risk per PCE or presence of ASCVD risk factors. | ||
USPSTF 11 | Low-dose aspirin, i.e. 75-100mg/dl | 40-59 years | 10 years ASCVD risk factors above 10% with low bleeding risk. | ||
ADA12 | At the dose of 75-162 mg/day | ≥50 years | Diabetes with a history of ASCVD | ||
ASCVD | |||||
LAI4 | Low-dose | NA | Coronary calcium scores above 100. | ||
Statins | |||||
AHA10 | High intensity Moderate intensity | 20-75 years 40-74 | LDL-C above 190 mg/dl T2DM for more than ten years | ||
USPSTFA11,12 | Moderate intensity | 40-75 | No history of CVD, 1 or more CVD risk factors and 10 year CVD event risk of 7.5% | ||
ADA12 | High intensity Moderate intensity Initiate intensity | 40-75 years 40-75 years 20-39 years | Diabetes with high CV risk Without a history of ASCVD Diabetes with an additional risk factor for ASCVD | ||
LAI4 | Early and aggressive therapy | NA | Individuals with signs of subclinical atherosclerosis. | ||
AHA; American Heart Association, USPSTF; United States Preventive Services Task Force, ADA; American Diabetes Association, LAI; Lipid Association of India | |||||
Key Studies Supporting Efficacy of Statins & Aspirin:
The Antithrombotic Trialists' (ATT) Collaboration found that adding aspirin to a statin regimen reduced major vascular events risk.13 A Khan SU et al. meta-analysis showed that combining statins with aspirin significantly reduced myocardial infarction(MI) risk without increasing bleeding risk.14 Zhang et al. demonstrated in a study including 127 ischemic stroke patients that the atorvastatin-aspirin combination significantly lowered cerebrovascular events and ischemic stroke recurrence compared to aspirin alone, suggesting benefits in treating ASCVD, regulating cholesterol, and improving quality of life.15
Challenges in Implementation
Clinical inertia remains among Indian physicians concerning polypill utilization16, with statin non-adherence frequently attributed to misconceptions, perceived necessity, and fears of over-prescription.17There are also concerns regarding the bleeding risks and GI tolerance associated with the use of aspirin in primary prevention.
Strategies for Effective Implementation – Effectively Applying Clinical Evidence in Clinical Care
The CVD epidemic in India is marked by elevated risk, earlier onset, higher case fatality, and increased premature mortality, underscoring the need for effective implementation of guideline-based treatments and appropriate application to aspirin and statin therapy when indicated.4Enteric-coated aspirin tablets have been shown to prevent aspirin absorption in the stomach, thus hypothetically decreasing its gastrointestinal toxicity.18
Aspirin-Guide App.-Allows Appropriate Eligibility for Aspirin Use in ASCVD Prevention: The Aspirin-Guide app developed by Brigham and Women’s Hospital and Harvard Medical School researchers assist clinicians in determining the appropriateness of low-dose aspirin for ASCVD prevention by weighing cardiovascular benefits against bleeding risks. It considers factors such as ASCVD history, age, gender, ethnicity, smoking, hypertension, diabetes, dyslipidemia, systolic blood pressure & cholesterol levels, and recent NSAID or steroid use. This app aids in informed decision-making when no major contraindications are present. Additionally, implementing patient-centric strategies, including multidisciplinary care, motivational counseling, patient empowerment, and effective communication, is essential.19
Summary
ASCVD is one major issue among young Indians. Clinical evidence and guidelines acknowledged that combining aspirin with statins benefits primary CVD prevention. Clinical challenges can be overcome by regular evaluation of aspirin and statin for high-CV-risk patients, accurate risk stratification, and comprehensive education and monitoring, which are crucial for improving outcomes. Utilizing digital tools like the Aspirin-Guide app could help optimize aspirin use in ASCVD prevention.
References:
1. Duell, P Barton et al. “The epidemic of atherosclerotic cardiovascular disease in India.” Journal of clinical lipidology vol. 14,2 (2020): 170-172. doi:10.1016/j.jacl.2020.01.010
2. Ranganath Muniyappa, Satish Babu K Narayanappa, Disentangling Dual Threats: Premature Coronary Artery Disease and Early-Onset Type 2 Diabetes Mellitus in South Asians, Journal of the Endocrine Society, Volume 8, Issue 1, January 2024, bvad167, https://doi.org/10.1210/jendso/bvad167
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. 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. Boakye, Ellen et al. “Aspirin for cardiovascular disease prevention among adults in the United States: Trends, prevalence, and participant characteristics associated with use.” American journal of Preventive Cardiology vol. 8 100256. 22 Sep. 2021, doi:10.1016/j.ajpc.2021.100256
6. Gidding SS. Addressing Knowledge Gaps in the Primary Prevention of Atherosclerotic Heart Disease. J Am Heart Assoc. 2024;13(6):e033991. doi:10.1161/JAHA.123.033991
7. Pavlović J, Greenland P, Deckers JW, et al. Assessing gaps in cholesterol treatment guidelines for primary prevention of cardiovascular disease based on available randomized clinical trial evidence: The Rotterdam Study. Eur J Prev Cardiol. 2018;25(4):420-431. doi:10.1177/2047487317743352
8. AMBIKA GOPALAKRISHNAN UNNIKRISHNAN, ASHOK KUMAR DAS, BANSHI D. SABOO, SANJAY KALRA; 2213-PUB: Management Practices in Indian Type 2 Diabetes Mellitus (T2DM) Participants With or Without Comorbidities in Real-World LEADD (Learnings with Experts to Advance Diabetic Dyslipidemia Management) Study. Diabetes 1 June 2019; 68 (Supplement_1): 2213–PUB. https://doi.org/10.2337/db19-2213-PUB
9. Liu, T., Zuo, R., Wang, J. et al. Cardiovascular disease preventive effects of aspirin combined with different statins in the United States general population. Sci Rep 13, 4585 (2023). https://doi.org/10.1038/s41598-023-31739-w
10. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577–1584. doi:10.1001/jama.2022.4983
11. USPSTF. Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication. 2022. Retreived on 23rdth July 2024 from https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/aspirin-to-prevent-cardiovascular-disease-preventive-medication
12. American Diabetes Association Professional Practice Committee; 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2024. Diabetes Care 1 January 2024; 47 (Supplement_1): S179–S218.
13. Antithrombotic Trialists' (ATT) Collaboration. Baigent C., Blackwell L., et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet. 2009;373:1849–1860.
14. Khan SU, Lone AN, Kleiman NS, et al. Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories. JACC Adv. 2023;2(2):100197. Published 2023 Feb 8. doi:10.1016/j.jacadv.2022.100197
15. Zhongbo Zhang1, Xinzhe Yao1, Minghua Wang, Yudiao Huang, Tong Shen, Weinan Zhang, Yingying Liu. Therapeutic effects of aspirin combined with atorvastatin on ischemic strokes.2018.Int J Clin Exp Med 2018;11(10):11104-11111
16. Salam, Abdul et al. “Barriers and Facilitators to the Use of Cardiovascular Fixed-Dose Combination Medication (Polypills) in Andhra Pradesh, India: A Mixed-Methods Study.” Global heart vol. 14,3 (2019): 303-310. doi:10.1016/j.gheart.2019.07.002
17. Desai, Nihar R et al. “Nonadherence to lipid-lowering therapy and strategies to improve adherence in patients with atherosclerotic cardiovascular disease.” Clinical cardiology vol. 46,1 (2023): 13-21. doi:10.1002/clc.23935
18. Ihm, Sang Hyun et al. “Interventions for Adherence Improvement in the Primary Prevention of Cardiovascular Diseases: Expert Consensus Statement.” Korean Circulation Journal vol. 52,1 (2022): 1-33. doi:10.4070/kcj.2021.0226
