Patients with diabetes mellitus have an increased risk of cardiovascular complications in the long run. Better control of hyperglycemia, along with other cardiovascular risk factors, has been tied to a reduction in atherosclerotic cardiovascular disease (ASCVD) and death in both type 1 and type 2 diabetes mellitus. However, the burden of death and hospitalization for ASCVD in diabetes patients continues to be twice that in the matched non-diabetic population.¹

Lifestyle interventions, as well as drugs like statins and low-dose aspirin, may have beneficial effects in patients with diabetes as they target one or multiple pathways accountable for accelerated atherosclerosis in these patients, such as endothelial dysfunction, platelet activation, low-grade inflammation, and oxidative stress.¹

Aspirin is commonly used for ASCVD prevention. It reduces the risk of atherothrombosis by irreversible inhibition of platelet function. While the drug is widely recommended for secondary prevention of ASCVD, its use in primary prevention has been debated.² The 2019 ESC guidelines recommend that low-dose aspirin may be considered in primary prevention in patients with diabetes at high and very high cardiovascular risk when there are no clear contraindications.3 The 2021 American Diabetes Association (ADA) Standards of Care also recommend considering aspirin therapy (75–162 mg/day) in primary prevention in patients with diabetes having an increased cardiovascular risk, following consideration of the benefits vs. the comparable increased risk of bleeding.⁴

Bugiardini and colleagues recently evaluated 12,123 patients presenting to the hospital with acute coronary syndromes as the first manifestation of CV disease between 2010 and 2019 in the ISACS-TC multicenter registry. The risk of STEMI was lower in those who took aspirin, irrespective of sex or age. Patients with diabetes obtained considerable benefit from aspirin use in the presence of multiple risk factors.⁵

Aspirin therapy should therefore be considered in primary prevention for patients with diabetes at high cardiovascular risk.

Additionally, amid the ongoing COVID-19 pandemic, there have been reports of pancreatitis in COVID-19 patients.6 Pancreas is a potential target for the SARS-CoV-2 virus as ACE2 is highly expressed here.⁶ Pancreatitis can also occur following cytokine storm and multi-organ dysfunction. The interplay between COVID-19 and the pancreatic endocrine system raises concern for patients with diabetes who contract the virus. COVID-19 infection can impair glycemic control by damaging the pancreatic beta cells.⁷

While diabetes is linked with an increased risk for developing severe COVID-19, new-onset diabetes has also been reported in patients with COVID-19. The virus seems to alter glucose metabolism that may complicate the pathophysiology of preexisting diabetes, or give way to novel mechanisms of disease.⁸

Type 2 diabetes is linked with greater atherosclerotic plaque burden, higher atheroma volume, as well as smaller coronary artery lumen diameter.⁹ It is associated with a prothrombotic state and an increased risk of thromboembolic events.¹⁰ In COVID-19 infection, inflammation induces cytokine storm, which results in an increased risk of vascular hyperpermeability, multi-organ failure, and death. This infection tends to increase the coagulation activity.¹⁰

Hence, COVID-19 in patients with diabetes seems to worsen the prognosis even further. COVID-19 patients who have underlying cardiovascular and metabolic disorders have a greater inflammatory response and hypercoagulant state, leading to worse clinical outcomes.¹¹

It has been proposed that patients with COVID-19 can benefit from the use of aspirin. Aspirin can inhibit viral replication, has anticoagulant, anti-platelet aggregation, and anti-inflammatory properties. Early use of this drug in COVID-19 patients could potentially limit the incidence of severe and critical cases. It may also decrease the length of hospital stay as well as the incidence of cardiovascular complications.¹² Aspirin can aid in preventing thromboinflammation, pulmonary embolism, and thrombosis seen in COVID-19 patients. Researchers suggest that aspirin should be started at the earliest in patients infected with COVID-19.¹³ A retrospective, observational cohort study noted that aspirin use was associated with less mechanical ventilation and ICU admission in hospitalized COVID-19 patients. It was also tied to a reduced risk of in-hospital mortality.¹⁴

Considering the available evidence, it seems plausible to consider the use of this drug in COVID-19 patients as well as in patients with diabetes as a primary prevention strategy.

Aspirin may be considered in patients with high cardiovascular risk with low bleeding risk. The treatment should be individualized, and the benefit/risk profile of aspirin therapy could be improved by the inclusion of a PPI in the treatment strategy.¹

References

1. Rocca B, Patrono C. Aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: A new perspective. Diabetes Research and Clinical Practice (2020). DOI: https://doi.org/10.1016/j.diabres.2020.108008.
2. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Sep, 74 (10) e177–e232.
3. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). European Heart Journal 2020;41(2):255–323.
4. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021;44(Suppl. 1): S125–S150.
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8. New-Onset Diabetes in Covid-19. N Engl J Med 2020; 383:789-790.
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10. Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020;8(9):782-792.
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12. Should aspirin be used for prophylaxis of COVID-19-induced coagulopathy? Medical Hypotheses 2020;144:109975.
13. Acetylsalicylic acid (Aspirin): a potent medicine for preventing COVID-19 deaths caused by thrombosis and pulmonary embolism. European Review for Medical and Pharmacological Sciences 2020;24:9244-9245.
14. Chow J, Khanna A, Kethireddy S, et al. Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19. Anesthesia & Analgesia 2020 October 21. DOI: 10.1213/ANE.0000000000005292