Pleiotropic effects of acetylsalicylic acid
DOI: 10.32364/2587-6821-2024-8-1-5
M.D. Smirnova
Acad. E.I. Chazov National Medical Research Center of Cardiology, Moscow, Russian Federation
Currently, researchers are investigating new mechanisms of action and potential applications of acetylsalicylic acid (ASA). This article summarizes recent studies on the use of ASA for primary prevention of cardiovascular complications (CVC), cancer, and chronic obstructive pulmonary disease (COPD) in progressive chronic kidney disease (CKD). The article discusses the efficacy and safety of ASA in patients with diabetes, COPD, CKD, and subclinical atherosclerosis of brachiocephalic arteries. ASA is a promising tool for primary prevention of CVC and progression of COPD and its complications, as well as malignant diseases. The safety profile of ASA is also addressed. The optimal dosage form of ASA that is both effective and safe is an important factor that should be considered when prescribing ASA for long-term use. Enteric-coated ASA is now widely used due to its diminished negative effect on gastrointestinal mucosa and improved safety.
Keywords: primary prevention, acetylsalicylic acid, antiplatelet therapy, cardiovascular complications, chronic kidney disease, chronic obstructive pulmonary disease, diabetes.
For citation: Smirnova M.D. Pleiotropic effects of acetylsalicylic acid. Russian Medical Inquiry. 2024;8(1):31–36 (in Russ.). DOI: 10.32364/2587-6821-2024-8-1-5.
About the author:
Maria D. Smirnova — Dr. Sc. (Med.), senior researcher of the Department of Treatment and Diagnostic Technologies of the A.L. Myasnikov Research Institute of Clinical Cardiology, Acad. E.I. Chazov National Medical Research Center of Cardiology; 15А, 3rd Cherepkovskaya str., Moscow, 121552, Russian Federation; ORCID iD 0000-0001-6515-3882.
Contact information: Maria D. Smirnova, e-mail: naliya1@yandex.ru.
Financial Disclosure: the author has no a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 11.01.2024.
Revised 05.02.2024.
Accepted 29.02.2024.
References
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15. Gallagher H., Dumbleton J., Maishman T. et al. Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease. Trials. 2022;23(1):331. DOI: 10.1186/s13063-022-06132-z.
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21. Hayashi H., Fukutomi Y., Mitsui C. et al. Omalizumab for aspirin hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease. A randomized controlled trial. Am J Respir Crit Care Med. 2020;201(12):1488–1498. DOI: 10.1164/rccm.201906-1215OC.
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24. Fawzy A., Putcha N., Aaron C.P. et al. Aspirin use and respiratory morbidity in COPD: a propensity score-matched analysis in subpopulations and intermediate outcome measures in COPD study. Chest. 2019;155(3):519–527. DOI: 10.1016/j.chest.2018.11.028.
25. Bakshi A., Suissa S. Effectiveness of Aspirin in COPD: Biases in the Observational Studies. COPD. 2021;18(4):449–455. DOI: 10.1080/15412555.2021.1963696.
26. Goto T., Faridi M.K., Camargo C.A., Hasegawa K. The association of aspirin use with severity of acute exacerbation of chronic obstructive pulmonary disease: a retrospective cohort study. NPJ Prim Care Respir Med. 2018;28(1):7. DOI: 10.1038/s41533-018-0074-x.
27. Ramos-Nino M.E., MacLean C.D., Littenberg B. Association between the prevalence of obstructive lung disease and the use of aspirin in a diabetic population. Interv Pulmonol (Middlet). 2022;1(1):5–10.
28. Morris T., Stables M., Hobbs A. et al. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol. 2009;183(3):2089–2096. DOI: 10.4049/jimmunol.0900477.
29. Baandrup L., Kjaer S.K., Olsen J.H. et al. Low-dose aspirin use and the risk of ovarian cancer in Denmark. Ann Oncol. 2015;26(4):787–792. DOI: 10.1093/annonc/mdu578.
30. Huang W.K., Chiou M.J., Yu K.H. et al. The association between low-dose aspirin use and the incidence of colorectal cancer: a nationwide cohort study. Aliment Pharmacol Ther. 2013;38(4):432–439. DOI: 10.1111/apt.12388.
31. Lapi F., Levi M., Simonetti M. et al. Risk of prostate cancer in low-dose aspirin users: A retrospective cohort study. Int J Cancer. 2016;139(1):205–211. DOI: 10.1002/ijc.30061.
32. Yu S.Y., Ip M.S., Li X. et al. Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study. PLoS Med. 2022;19(1):e1003880. DOI: 10.1371/journal.pmed.1003880.
33. Ye S., Lee M., Lee D. et al. Association of Long-term Use of Low-Dose Aspirin as Chemoprevention With Risk of Lung Cancer. JAMA Netw Open. 2019;2(3):e190185. DOI: 10.1001/jamanetworkopen.2019.0185.
34. Kang J., Jeong S.M., Shin D.W. et al. The Associations of Aspirin, Statins, and Metformin With Lung Cancer Risk and Related Mortality: A Time-Dependent Analysis of Population-Based Nationally Representative Data. J Thorac Oncol. 2021;16(1):76–88. DOI: 10.1016/j.jtho.2020.08.021.
35. Rothwell P.M., Wilson M., Price J.F. et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591–1601. DOI: 10.1016/S0140-6736(12)60209-8.
36. Cao Y., Nishihara R., Wu K. et al. Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer. JAMA Oncol. 2016;2(6):762–769. DOI: 10.1001/jamaoncol.2015.6396.
37. Holick C.N., Michaud D.S., Leitzmann M.F. et al. Aspirin use and lung cancer in men. Br J Cancer. 2003;89(9):1705–1708. DOI: 10.1038/sj.bjc.6601343.
38. Sekine Y., Suzuki H., Yamada Y. et al. Severity of chronic obstructive pulmonary disease and its relationship to lung cancer prognosis after surgical resection. Thorac Cardiovasc Surg. 2013;61(2):124–130. DOI: 10.1055/s-0032-1304543.
39. Cho M.S., Bottsford-Miller J., Vasquez H.G. et al. Platelets increase the proliferation of ovarian cancer cells. Blood. 2012;120(24):4869–4872. DOI: 10.1182/blood-2012-06-438598.
40. Rolin S., Masereel B., Dogneґ J.M. Prostanoids as pharmacological targets in COPD and asthma. Eur J Pharmacol. 2006;533(1–3):89–100. DOI: 10.1016/j.ejphar.2005.12.058.
41. Khan P., Manna A., Saha S. et al. Aspirin inhibits epithelial-tomesenchymal transition and migration of oncogenic K-ras-expressing non-small cell lung carcinoma cells by down-regulating E-cadherin repressor Slug. BMC Cancer. 2016;16:39. DOI: 10.1186/s12885-016-2078-7.
42. Yang L., Lv Z., Xia W. et al. The effect of aspirin on circulating tumor cells in metastatic colorectal and breast cancer patients: a phase II trial study. Clin Transl Oncol. 2018;20(7):912–921. DOI: 10.1007/s12094-017-1806-z.
43. Hu X., Hu Y., Sun X. et al. Effect of aspirin in patients with established asymptomatic carotid atherosclerosis: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1041400. DOI: 10.3389/fphar.2022.1041400.
44. Li Z., Xiang S., Du Y. et al. Preoperative Use of Aspirin in Total Knee Arthroplasty: Safe or Not? Orthop Surg. 2022;14(8):1673–1680. DOI: 10.1111/os.13321.
45. Dietz R., Rauch B., German Society of Cardiology — Heart Circulation Research et al. Leitlinie zur Diagnose und Behandlung der chronischen koronaren Herzerkrankung der Deutschen Gesellschaft für Kardiologie — Herz und Kreislaufforschung (DGK). In Kooperation mit der Deutschen Gesellschaft für Prävention und Rehabilitation von Herz-Kreislauferkrankungen (DGPR) und der Deutschen Gesellschaft für Thorax-, Herz- und Gefässchirurgie (DGTHG). Z Kardiol. 2003;92(6):501–521(in German). PMID: 12905980.
2. Amann R., Peskar B.A. Anti-inflammatory effects of aspirin and sodium salicylate. Eur J Pharmacol. 2002;447(1):1–9. DOI: 10.1016/s0014-2999(02)01828-9.
3. Derry S., Moore R.A. Single dose oral aspirin for acute postoperative pain in adults. Cochrane Database Syst Rev. 2012;2012(4):CD002067. DOI: 10.1002/14651858.CD002067.pub2.
4. McCarthy D.M. Efficacy and gastrointestinal risk of aspirin used for the treatment of pain and cold. Best Pract Res Clin Gastroenterol. 2012;26(2):101–112. DOI: 10.1016/j.bpg.2012.01.008.
5. Eccles R., Loose I., Jawad M., Nyman L. Effects of acetylsalicylic acid on sore throat pain and other pain symptoms associated with acute upper respiratory tract infection. Pain Med. 2003;4(2):118–124. DOI: 10.1046/j.1526-4637.2003.03019.x.
6. Bachert C., Chuchalin A.G., Eisebitt R. et al. Aspirin compared with acetaminophen in the treatment of fever and other symptoms of upper respiratory tract infection in adults: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose, 6-hour dose-ranging study. Clin Ther. 2005;27(7):993–1003. DOI: 10.1016/j.clinthera.2005.06.002.
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. 2002;324:71–86. DOI: 10.1136/bmj.324.7329.71.
8. Elwood P.C., Cochrane A.L., Burr M.L. et al. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. Br Med J. 1974;1(5905):436–440. DOI: 10.1136/bmj.1.5905.436.
9. Baigent C., Blackwell L., Collins R. et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–1860. DOI: 10.1016/S0140-6736(09)60503-1.
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11. American Diabetes Association Professional Practice Committee. Summary of Revisions: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S4–S7. DOI: 10.2337/dc22-Srev.
12. Valgimigli M., Bueno H., Byrne R.A. et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018;39(3):213–260. DOI: 10.1093/eurheartj/ehx419.
13. Shi Y., Tham Y.C., Cheung N. et al. Is aspirin associated with diabetic retinopathy? The Singapore Epidemiology of Eye Disease (SEED) study. PLoS One. 2017;12(4):e0175966. DOI: 10.1371/journal.pone.0175966.
14. Mann J.F.E., Joseph Ph., Gao P. et al. MO201: Effects of Aspirin in Primary Prevention of Cardiovascular (CV) Disease in People with Chronic Kidney Disease (CKD): Results of the TIPS3 Trial. Nephrology Dialysis Transplantation. 2022;37(Issue Supplement_3):i138. DOI: 10.1093/ndt/gfac066.103.
15. Gallagher H., Dumbleton J., Maishman T. et al. Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease. Trials. 2022;23(1):331. DOI: 10.1186/s13063-022-06132-z.
16. Tsai M.H., Liou H.H., Huang Y.C. et al. Hazardous Effect of Low-Dose Aspirin in Patients with Predialysis Advanced Chronic Kidney Disease Assessed by Machine Learning Method Feature Selection. Healthcare (Basel). 2021;9(11):1484. DOI: 10.3390/healthcare9111484.
17. Meng Y., Lin Y., Zhang J.W. et al. Aspirin intervention before ICU admission reduced the mortality in critically ill patients with acute kidney injury: results from the MIMIC-IV. Front Pharmacol. 2023;14:1292745. DOI: 10.3389/fphar.2023.1292745.
18. Rothenberg F.G., Clay M.B., Jamali H., Vandivier-Pletsch R.H. Systematic review of β blocker, aspirin, and statin in critically ill patients: importance of severity of illness and cardiac troponin. J Investig Med. 2017;65(4):747–753. DOI: 10.1136/jim-2016-000374.
19. Garg A.X., Kurz A., Sessler D.I. et al. Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial. JAMA. 2014;312(21):2254–2264. DOI: 10.1001/jama.2014.15284.
20. Liu H., Li J., Chen M., Yang T. et al. Meta-Analysis of Randomized and Observational Studies: Aspirin Protects from Cardiac Surgery-Associated Acute Kidney Injury. Heart Surg Forum. 2019;22(4):E301–E307. DOI: 10.1532/hsf.2419.
21. Hayashi H., Fukutomi Y., Mitsui C. et al. Omalizumab for aspirin hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease. A randomized controlled trial. Am J Respir Crit Care Med. 2020;201(12):1488–1498. DOI: 10.1164/rccm.201906-1215OC.
22. Hedman J., Kaprio J., Poussa T., Nieminen M.M. Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. Int J Epidemiol. 1999;28(4):717–722. DOI: 10.1093/ije/28.4.717.
23. Wenzel S.E. The role of leukotrienes in asthma. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2003;69(2–3):145–155. DOI: 10.1016/s0952-3278(03)00075-9.
24. Fawzy A., Putcha N., Aaron C.P. et al. Aspirin use and respiratory morbidity in COPD: a propensity score-matched analysis in subpopulations and intermediate outcome measures in COPD study. Chest. 2019;155(3):519–527. DOI: 10.1016/j.chest.2018.11.028.
25. Bakshi A., Suissa S. Effectiveness of Aspirin in COPD: Biases in the Observational Studies. COPD. 2021;18(4):449–455. DOI: 10.1080/15412555.2021.1963696.
26. Goto T., Faridi M.K., Camargo C.A., Hasegawa K. The association of aspirin use with severity of acute exacerbation of chronic obstructive pulmonary disease: a retrospective cohort study. NPJ Prim Care Respir Med. 2018;28(1):7. DOI: 10.1038/s41533-018-0074-x.
27. Ramos-Nino M.E., MacLean C.D., Littenberg B. Association between the prevalence of obstructive lung disease and the use of aspirin in a diabetic population. Interv Pulmonol (Middlet). 2022;1(1):5–10.
28. Morris T., Stables M., Hobbs A. et al. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol. 2009;183(3):2089–2096. DOI: 10.4049/jimmunol.0900477.
29. Baandrup L., Kjaer S.K., Olsen J.H. et al. Low-dose aspirin use and the risk of ovarian cancer in Denmark. Ann Oncol. 2015;26(4):787–792. DOI: 10.1093/annonc/mdu578.
30. Huang W.K., Chiou M.J., Yu K.H. et al. The association between low-dose aspirin use and the incidence of colorectal cancer: a nationwide cohort study. Aliment Pharmacol Ther. 2013;38(4):432–439. DOI: 10.1111/apt.12388.
31. Lapi F., Levi M., Simonetti M. et al. Risk of prostate cancer in low-dose aspirin users: A retrospective cohort study. Int J Cancer. 2016;139(1):205–211. DOI: 10.1002/ijc.30061.
32. Yu S.Y., Ip M.S., Li X. et al. Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study. PLoS Med. 2022;19(1):e1003880. DOI: 10.1371/journal.pmed.1003880.
33. Ye S., Lee M., Lee D. et al. Association of Long-term Use of Low-Dose Aspirin as Chemoprevention With Risk of Lung Cancer. JAMA Netw Open. 2019;2(3):e190185. DOI: 10.1001/jamanetworkopen.2019.0185.
34. Kang J., Jeong S.M., Shin D.W. et al. The Associations of Aspirin, Statins, and Metformin With Lung Cancer Risk and Related Mortality: A Time-Dependent Analysis of Population-Based Nationally Representative Data. J Thorac Oncol. 2021;16(1):76–88. DOI: 10.1016/j.jtho.2020.08.021.
35. Rothwell P.M., Wilson M., Price J.F. et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591–1601. DOI: 10.1016/S0140-6736(12)60209-8.
36. Cao Y., Nishihara R., Wu K. et al. Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer. JAMA Oncol. 2016;2(6):762–769. DOI: 10.1001/jamaoncol.2015.6396.
37. Holick C.N., Michaud D.S., Leitzmann M.F. et al. Aspirin use and lung cancer in men. Br J Cancer. 2003;89(9):1705–1708. DOI: 10.1038/sj.bjc.6601343.
38. Sekine Y., Suzuki H., Yamada Y. et al. Severity of chronic obstructive pulmonary disease and its relationship to lung cancer prognosis after surgical resection. Thorac Cardiovasc Surg. 2013;61(2):124–130. DOI: 10.1055/s-0032-1304543.
39. Cho M.S., Bottsford-Miller J., Vasquez H.G. et al. Platelets increase the proliferation of ovarian cancer cells. Blood. 2012;120(24):4869–4872. DOI: 10.1182/blood-2012-06-438598.
40. Rolin S., Masereel B., Dogneґ J.M. Prostanoids as pharmacological targets in COPD and asthma. Eur J Pharmacol. 2006;533(1–3):89–100. DOI: 10.1016/j.ejphar.2005.12.058.
41. Khan P., Manna A., Saha S. et al. Aspirin inhibits epithelial-tomesenchymal transition and migration of oncogenic K-ras-expressing non-small cell lung carcinoma cells by down-regulating E-cadherin repressor Slug. BMC Cancer. 2016;16:39. DOI: 10.1186/s12885-016-2078-7.
42. Yang L., Lv Z., Xia W. et al. The effect of aspirin on circulating tumor cells in metastatic colorectal and breast cancer patients: a phase II trial study. Clin Transl Oncol. 2018;20(7):912–921. DOI: 10.1007/s12094-017-1806-z.
43. Hu X., Hu Y., Sun X. et al. Effect of aspirin in patients with established asymptomatic carotid atherosclerosis: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1041400. DOI: 10.3389/fphar.2022.1041400.
44. Li Z., Xiang S., Du Y. et al. Preoperative Use of Aspirin in Total Knee Arthroplasty: Safe or Not? Orthop Surg. 2022;14(8):1673–1680. DOI: 10.1111/os.13321.
45. Dietz R., Rauch B., German Society of Cardiology — Heart Circulation Research et al. Leitlinie zur Diagnose und Behandlung der chronischen koronaren Herzerkrankung der Deutschen Gesellschaft für Kardiologie — Herz und Kreislaufforschung (DGK). In Kooperation mit der Deutschen Gesellschaft für Prävention und Rehabilitation von Herz-Kreislauferkrankungen (DGPR) und der Deutschen Gesellschaft für Thorax-, Herz- und Gefässchirurgie (DGTHG). Z Kardiol. 2003;92(6):501–521(in German). PMID: 12905980.
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