DOI: 10.31038/JCCP.2020324

The 2019 American Heart Association/American College of Cardiology guidelines for the primary prevention of atherosclerotic cardiovascular disease virtually preclude aspirin use for adults ages 40-70 unless at long-term high risk (>10% threshold by 10-year risk calculators) [1]. The cardiovascular complications of coronavirus-19 (COVID-19) infection may require us to reconsider this, however, to take short-term high risk into account. Likened to a cytokine tsunami,elevated levels of interleukin-6 and C-reactive protein predict cardiac and respiratory failure, indicatingthat inflammation mediates excess morbidity and mortality [2-4].While dipyridamole has been associated with clinical improvement which was not observed with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers [5,6], the effect of aspirin on clinical outcomeshas yet to be reported. Based on evidence that inhibition of inflammation prevents cardiovascular events andthat low-dose aspirinconclusively reducedfirst heart attacks in middle-aged men in the randomized controlled Physicians Health Study [7,8], this latter approach has been recommended to protect athletes from theincreased risk of event-related cardiac arrest and sudden death triggered by inflammation due to exertional rhabdomyolysis [9-11]. Aspirin’s anti-inflammatory and anti-thrombotic effects may mitigate pandemic-related increased short-term risk, perhaps bluntingthe surge in coronary heart disease deaths which have occurredunder such conditions [12]. C-reactive protein levels can reliably stratify risk for low-dose aspirin as have coronary artery calcium scores for statin therapy [13,14] (Table 1).

Prophylactic low-dose aspirin usefor susceptible individuals presents a window of opportunity toreduce the cardiovascularcomplications of COVID-19 infection ahead of the second wave anticipated by the United States Center for Disease Control [15]. Based on inflammation as the root cause of atherothrombosis, a predominance of current clinical evidencesupports this interventionwithout a randomized controlled clinical trial asnecessary for novel interventions such as the high-dose interleukin-1 receptor antagonist tocilizumab [16]. Revised guidelines for primary prevention to accommodate short-term high risk may facilitate this goal as accomplished by subspecialty societies for treating acute myocardial infarction [17]. Preventing fatal strokes in young persons might be anunintended collateral benefit [18].

Keywords

Aspirin, Coronary heart disease, COVID-19 pandemic, Primarycardiovascular prevention

References

1. Arnett DK, Blumenthal RS, Albert MA, Andrew B Buroker, Zachary D Goldberger, et al. (2019) 2019 ACC/AHA guidelines on the primary prevention of cardiovascular disease. J Am CollCardiol4:e177-e232. [crossref]
2. Long B, Brady WJ, Koyfman A, Gottlieb M (2020) Cardiovascular complications in COVID–19.Am J Emerg Med38: 1504-1507. [crossref]
3. Clerkin KJ, Fried JA, Raikhelker J, Gabriel Sayer, Jan M Griffin, et al. (2020) Coronavirus disease 2019 (COVID-19) and cardiovascular disease. Circulation141:1648-1655. [crossref]
4. Heriod T, Jurinovic V, Arnreich C, Brian J. Lipworth, Johannes C. Hellmuth, et al. (2020) Elevated levels of interleukin-6 and C-reactive protein predict the need for mechanical ventilation inCOVID-19. J Allergy Clin Immunol. 146: 128-136. [crossref]
5. Liu X, Li Z, Liu S, Sun J, Chen Z, et al. (2020) Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. ActaPharmaceuticaSinica B [crossref]
6. Guo T, Fan Y, Chen M, Xiaoyan Wu, Lin Zhang, et al. (2020) Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19).JAMA Cardiol 5:1-8. [crossref]
7. Ridker PM, Libby P, MacFadyen JG, Tom Thuren, Christie Ballantyne, et al. (2018) Modulation of the interleukin-6 signalingpathway and incidence rates of atherosclerotic events and all-cause mortality: analysis from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS).EurHeart J 39: 3499-3507. [crossref]
8. Steering Committee of the Physicians’ Health Study Research Group (1989) Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 321: 129-135. [crossref]
9. Siegel AJ (2015) Pre-race aspirin to protect susceptible runners from cardiac arrest during marathon: is opportunity knocking? Open Heart2:e000102. [crossref]
10. Siegel AJ, Noakes TD (2017) Can pre-race aspirin prevent sudden cardiac death during marathons? Br J Sports Med 51:1579-1581. [crossref]
11. Siegel AJ, Noakes TD (2019) Aspirin to prevent sudden cardiac death in athletes with high coronary artery calcium scores. Am J Med132:138-141. [crossref]
12. Madjid M, Miller CC, Zarubaev VV, Ivan G Marinich, Oleg I Kiselev, et al. (2007) Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease deaths: results from 8 years of autopsies in 34,892 subjects.Eur Heart J 28: 1205-1210. [crossref]
13. Greenland P, Blaha MJ, Budoff MJ, Erbel R, Watson KE (2018) Coronary calcium scores and cardiovascular risk.J Am CollCardiol72: 434-447. [crossref]
14. Siegel AJ (2020) Aspirin to Reduce Risk for Sudden Cardiac Death in Athletes with Elevated C-Reactive Protein Levels: Preventing exertional cardiac arrest in high-risk athletes.Am J Med133(9). doi.org/10.1016/j.amjmed.2020.04.004.
15. Sun LH (2020) CD director warns second wave of coronavirus is likely to be even more devastating.Washington Post.
16. Xu X, Han M, Li T, Wei Sun, Dongsheng Wang, et al. (2020) Effective treatment of severe COVID–19 patients with tocilizumab. ProcNatlAcadSci 117:10970-10975. [crossref]
17. SCAI, ACC and ACEP release consensus on management of AMI patients amid COVID-19–pandemic (2020) SCAI, ACC and ACEP release consensus on management of AMI patients amid COVID-19 pandemic.
18. Oxley TJ, Mocco J, Majidi S, Christopher P Kellner, HazemShoirah, et al. (2020) Large vessel strokes as a presenting feature of Covid-19 in the young. N Engl J Med. 382:e60. [crossref]