Antithrombotic therapy in patients with diabetes mellitus

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Abstract

The study discussed various possibilities of antithrombotic therapy in patients with diabetes mellitus. Patients with diabetes mellitus, regardless of whether they have cardiovascular diseases, have a high risk of thrombosis. A feature of the response to antiplatelet therapy is the higher resistance to acetylsalicylic acid and clopidogrel of patients with diabetes mellitus than patients without diabetes mellitus, which can reach 71.4% and 57.1%, respectively. With a decrease in the functional ability of the kidneys in patients with diabetic nephropathy, acetylsalicylic acid is a safe antiplatelet drug; the use of clopidogrel in these patients leads to an increase in the risk of general and cardiovascular mortality. In the absence of contraindications, acetylsalicylic acid is recommended for patients with diabetes mellitus for the secondary prevention of cardiovascular diseases and may be recommended for primary prevention in patients with high and very high cardiovascular risk. Clopidogrel is recommended for patients with diabetes mellitus only for the secondary prevention of intolerance to acetylsalicylic acid. With the development of acute coronary syndrome, patients with diabetes mellitus received double antiplatelet therapy using acetylsalicylic acid and any P2Y12 receptor blocker. In patients who received percutaneous coronary intervention, prasugrel or ticagrelor is recommended as the second component. Double antiplatelet therapy extended for >12 months is indicated for patients with diabetes mellitus with a very high cardiovascular risk and good tolerability. In non-valvular atrial fibrillation, direct oral anticoagulants, in the absence of contraindications, are the drugs of choice in patients with diabetes and creatinine clearance > 30 mL/min for dabigatran and > 15 mL/min for rivaroxaban and apixaban. With the development of terminal renal insufficiency, only warfarin has proven effectiveness. Combined antiplatelet and anticoagulant therapy is indicated for diabetes mellitus with coexisting atherosclerotic diseases with a high risk of thrombotic and low risk of hemorrhagic complications.

About the authors

Evgeniy V. Kryukov

Military Medical Academy of S.M. Kirov

Email: ilikedm@mail.ru
ORCID iD: 0000-0002-8396-1936
SPIN-code: 3900-3441
Scopus Author ID: 57208311867
ResearcherId: AAO-9491-2020

doctor of medical sciences, professor

Russian Federation, Saint Petersburg

Alexey N. Kuchmin

Military Medical Academy of S.M. Kirov

Email: ilikedm@mail.ru
ORCID iD: 0000-0003-2888-9625
SPIN-code: 7787-1364

doctor of medical science, professor

Russian Federation, Saint Petersburg

Elena P. Umanskaya

Military Medical Academy of S.M. Kirov

Email: elenaumansk@mail.ru
SPIN-code: 2690-3373

candidate of medical sciences

Russian Federation, Saint Petersburg

Mikhail B. Nagorny

Military Medical Academy of S.M. Kirov

Author for correspondence.
Email: ilikedm@mail.ru
SPIN-code: 1861-8100

candidate of medical sciences

Russian Federation, Saint Petersburg

Andrey A. Shevelev

Military Medical Academy of S.M. Kirov

Email: tuostax@mail.ru
SPIN-code: 5766-8003

candidate of medical sciences

Russian Federation, Saint Petersburg

Anna M. Rozhkova

Military Medical Academy of S.M. Kirov

Email: anna_rozhkova@mail.ru
ORCID iD: 0000-0002-5778-1237

therapist

Russian Federation, Saint Petersburg

References

  1. Petrik GG, Pavlishhuk SA, Kosmacheva ED. Diabetes mellitus and cardiovascular complications: focus on hemostasis. Russian Journal of Cardiology. 2014;(3):114–118. (In Russ.). doi: 10.15829/1560-4071-2014-3-114-118
  2. Sergienko IV, Ansheles AA, Khalimov YuSh, et al. Kardiologicheskie aspekty sakharnogo diabeta 2 tipa. Moscow: Pero; 2018. 68 p. (In Russ.).
  3. Krjukov EV, Kuchmin AN, Umanskaja EP. The main pathogenetic mechanisms of hypercoagulation in diabetes and the possibility of its drug correction. Bulletin of the Russian Military Medical Academy. 2021;(2):165–174. (In Russ.). doi: 10.17816/brmma64995
  4. Salukhov VV, Gulyaev NI, Chepel’ AI, et al. Preventive antiplatelet therapy of ischemic heart disease complications in conditions of variability of platelet response. Bulletin of the National Medical and Surgical Center named after N.I. Pirogov. 2020;15(4):82–90. (In Russ.). doi: 10.25881/BPNMSC.2020.20.88.016
  5. Cosentino F, Grant PJ, Aboyans V, et al. 2019 Rekomendatsii ESC/EASD po sakharnomu diabetu, prediabetu i serdechno-sosudistym zabolevaniyam. Russian Journal of Cardiology. 2020;25(4):3839. (In Russ.). doi: 10.15829/1560-4071-2020-3839
  6. 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(7329):71–86. doi: 10.1136/bmj.324.7329.71
  7. Eikelboom JW, Hirsh J, Spencer FA, et al. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis. Chest. 2012;141(2):e89S–e119S. doi: 10.1378/chest.11-2293
  8. Bailey MA, Aggarwal R, Bridge KI, et al. Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm. J Thromb Haemost. 2015;13(5):795–801. doi: 10.1111/jth.12872
  9. Tehrani S, Antovic A, Mobarrez F, et al. High-dose aspirin is required to influence plasma fibrin network structure in patients with type 1 diabetes. Diabetes Care. 2012;35(2):404–408. doi: 10.2337/dc11-1302
  10. Ushkalova EA. Aspirin resistance: development mechanisms, diagnostic methods and clinical significance. Farmateca. 2006;(13):35–41. (In Russ.).
  11. Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov. 2003;2(1):15–28. doi: 10.1038/nrd985
  12. Lordkipanidzé M. Advances in monitoring of aspirin therapy. Platelets. 2012;23(7):526–536. doi: 10.3109/09537104.2012.711865
  13. Cipollone F, Rocca B, Patrono C. Ciclooxygenase-2 expression and inhibition in atherothrombosis. Arterioscler Thromb Vasc. 2004;24(2):246–255.
  14. Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008;26(336):195–198. doi: 10.1136/bmj.39430.529549
  15. Watala C, Pluta J, Golanski J, et al. Increased protein glycation in diabetes mellitus is associated with decreased aspirin-mediated protein acetylation and reduced sensitivity of blood platelets to aspirin. J Mol Med (Berl.) 2005;83(2):148–158. doi: 10.1007/s00109-004-0600-x
  16. Russo I, Viretto M, Barale C, et al. High glucose inhibits the aspirin-induced activation of the nitric oxide/cGMP/cGMP-dependent protein kinase pathway and does not affect the aspirin-induced inhibition of thromboxane synthesis in human platelets. Diabetes. 2012;61(11):2913–2921. doi: 10.2337/db12-0040
  17. Dillinger JG, Drissa A, Sideris G, et al. Biological efficacy of twice daily aspirin in type 2 diabetic patients with coronary artery disease. Am Heart J. 2012;164(4):600–606. doi: 10.1016/j.ahj.2012.06.008
  18. García Rodríguez LA, Hernández-Díaz S, de Abajo FJ. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol. 2001;52(5): 563–571. doi: 10.1046/j.0306-5251.2001.01476.x
  19. Bowman L, Mafham M, Stevens W, et al. ASCEND: A Study of Cardiovascular Events in Diabetes: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. Am Heart J. 2018;198:135–144. doi: 10.1016/j.ahj.2017.12.006
  20. Capodanno D, Angiolillo DJ. Antithrombotic therapy in patients with chronic kidney disease. Circulation. 2012;125(21):2649–2661. doi: 10.1161/circulationaha.111.084996
  21. Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol. 2010;50(2):126–142. doi: 10.1177/0091270009343005
  22. Fork FT, Lafolie P, Tóth E, Lindgärde F. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand. J Gastroenterol. 2000;35(5):464–469. doi: 10.1080/003655200750023705
  23. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2008;118(18):1894–1909. doi: 10.1161/CIRCULATIONAHA.108.191087
  24. Snoep JD, Hovens MM, Eikenboom JC, et al. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J. 2007;154(2):221–231. doi: 10.1016/j.ahj.2007.04.014
  25. Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006;108(7):2244–2247. doi: 10.1182/blood-2006-04-013052
  26. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304(16):1821–1830. doi: 10.1001/jama.2010.1543
  27. Htun P, Fateh-Moghadam S, Bischofs C, et al. Low responsiveness to clopidogrel increases risk among CKD patients undergoing coronary intervention. J Am Soc Nephrol. 2011;22(4):627–633. doi: 10.1681/ASN.2010020220
  28. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation. 2003;107(1):32–37. doi: 10.1161/01.cir.0000047060.60595.cc
  29. Serebruany VL, Malinin AI, Callahan KP, et al. Statins do not affect platelet inhibition with clopidogrel during coronary stenting. Atherosclerosis. 2001;159(1):239–241. doi: 10.1016/s0021-9150(01)00606-2
  30. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363(20):1909–1917. doi: 10.1056/NEJMoa1007964
  31. Wu ZK, Wang JJ, Wang T, et al. Clopidogrel resistance response in patients with coronary artery disease and metabolic syndrome: the role of hyperglycemia and obesity. J Geriatr Cardiol. 2015;12(4):378–382. doi: 10.11909/j.issn.1671-5411.2015.04.009
  32. Ferguson AD, Dokainish H, Lakkis N. Aspirin and clopidogrel response variability: review of the published literature. Tex Heart Inst J 2008;35(3):313–320.
  33. Dasgupta A, Steinhubl SR, Bhatt DL, et al. Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial). Am J Cardiol. 2009;103(10): 1359–1363. doi: 10.1016/j.amjcard.2009.01.342
  34. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–1717. doi: 10.1056/NEJMoa060989
  35. Dedov II, Shestakova MV, Mayorova AYu, editors. Standards of specialized diabetes care. 10th ed. Moscow. 2021. 222 p. (In Russ.). DOI: doi: 10.14341/DM12802
  36. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494–502. doi: 10.1056/NEJMoa010746
  37. Steinhubl SR, Berger PB, Mann JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288(19): 411–2420. doi: 10.1001/jama.288.19.2411
  38. Gori AM, Marcucci R, Migliorini A, et al. Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents. J Am Coll Cardiol. 2008;52(9): 734–739. doi: 10.1016/j.jacc.2008.05.032
  39. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–2015. doi: 10.1056/NEJMoa0706482
  40. Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet. 2008;371(9621):1353–1363. doi: 10.1016/S0140-6736(08)60422-5
  41. Sanderson NC, Parker WAE, Storey RF. Ticagrelor: clinical development and future potential. Rev Cardiovasc Med. 2021;22(2):373–394. doi: 10.31083/j.rcm2202044
  42. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–1057. doi: 10.1056/NEJMoa0904327
  43. James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2010;122(11):1056–1067. doi: 10.1161/CIRCULATIONAHA.109.933796
  44. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371(23):2155–2166. doi: 10.1056/NEJMoa1409312
  45. Parker WA, Storey RF. Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54. Heart. 2016;102(10):83–789. doi: 10.1136/heartjnl-2015-307858
  46. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1082–1115. doi: 10.1016/j.jacc.2016.03.513
  47. Bohne LJ, Johnson D, Rose RA, et al. The Association Between Diabetes Mellitus and Atrial Fibrillation: Clinical and Mechanistic Insights. Front Physiol. 2019;10:135. doi: 10.3389/fphys.2019.00135
  48. Rizzo MR, Sasso FC, Marfella R, et al. Autonomic dysfunction is associated with brief episodes of atrial fibrillation in type 2 diabetes. J Diabetes Complicat. 2015;29(1):88–92. doi: 10.1016/j.jdiacomp.2014.09.002
  49. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 2016;37(38):2893–2962. doi: 10.1093/eurheartj/ehw210
  50. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–272. doi: 10.1378/chest.09-1584
  51. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955–962. doi: 10.1016/S0140-6736(13)62343-0
  52. Moiseev SV. Prevention of cardiovascular outcomes in diabetic patients with atrial fibrillation: direct oral anticoagulants or warfarin? Clinical Pharmacology and Therapy. 2019;28(3):5–13. (In Russ.). doi: 10.32756/0869-5490-2019-3-5-13
  53. Böhm M, Ezekowitz MD, Connolly J, et al. Changes in Renal Function in Patients With Atrial Fibrillation: An Analysis From the RE-LY Trial. J Am Coll Cardiol. 2015;65(23):2481–2493. doi: 10.1016/j.jacc.2015.03.577
  54. Del-Carpio Munoz F, Gharacholou SM, Munger TM, et al. Meta-Analysis of Renal Function on the Safety and Efficacy of Novel Oral Anticoagulants for Atrial Fibrillation. Am J Card. 2016;117(1):69–75. doi: 10.1016/j.amjcard.2015.09.046
  55. Steffel J, Verhamme P, Potpara TS, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330–1393. doi: 10.1093/eurheartj/ehy136
  56. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Russian Journal of Cardiology. 2017;22(7):7–86. (In Russ.). doi: 10.15829/1560-4071-2017-7-7-86
  57. Redondo M, Caliezi C, Biasiutti FD, et al. Increased fibrin monomer plasma concentration in stable coronary artery disease in patients without oral anticoagulation. Atherosclerosis. 2001;157(2):417–422. doi: 10.1016/s0021-9150(00)00731-0
  58. Tosi F, Micaglio R, Sandri M, et al. Increased plasma thrombin potential is associated with stable coronary artery disease: An angiographically-controlled study. Thromb Res. 2017;155:16–22. doi: 10.1016/j.thromres.2017.04.021
  59. Corrado E, Rizzo M, Muratori I, et al. Association of elevated fibrinogen and C-reactive protein levels with carotid lesions in patients with newly diagnosed hypertension or type II diabetes. Arch Med Res. 2006;37(8):1004–1009. doi: 10.1016/j.arcmed.2006.06.005
  60. Festa A, Williams K, Tracy RP, et al. Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes. Circulation. 2006;113(14):1753–1759. doi: 10.1161/CIRCULATIONAHA.106.616177
  61. Gibson CM, Mega JL, Burton P, et al. Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome. Am Heart J. 2011;161(5):815–821.e6. doi: 10.1016/j.ahj.2011.01.026
  62. Connolly SJ, Eikelboom JW, Bosch J, et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391(10117):205–218. doi: 10.1016/S0140-6736(17)32458-3
  63. Knuuti J. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Russian Journal of Cardiology. 2020;25(2):3757. (In Russ.). doi: 10.15829/1560-4071-2020-2-3757

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Copyright (c) 2022 Kryukov E.V., Kuchmin A.N., Umanskaya E.P., Nagorny M.B., Shevelev A.A., Rozhkova A.M.

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