Diabetes mellitus and resistance to therapy with ADP-receptor antagonists: Importance, possibilities of detection and therapeutic influence


Authors: Matej Samoš;  Tomáš Bolek;  František Kovář;  Peter Galajda;  Marián Mokáň
Authors‘ workplace: I. interná klinika, Jesseniova LF UK a UNM, Martin
Published in: AtheroRev 2018; 3(1): 34-39
Category: Reviews

Overview

Diabetes mellitus is connected with clopidogrel resistance, an independent risk factor of future ischemic events in patients undergoing percutaneous coronary interventions, including stent thrombosis. On-treatment platelet reactivity assessment should be considered especially in clopidogrel-treated DM patients. Platelet function testing might be performed either with nonspecific methods, such as light transmission aggregometry as a golden standard, or with a specific method – VASP (vasodilator stimulated phosphoprotein) phosphorylation assessment. New ADP-receptor blockers – prasugrel and ticagrelor – seem to be more effective for overcoming clopidogrel resistance in diabetic patients. These agents both show rapid and consistent platelet inhibition. Tailored clopidogrel therapy may be considered in selected cases; however, this strategy has lower evidence from clinical trials. The therapeutic goal is to achieve sufficient inhibition of ADP-signaling pathway, which will reduce the risk of future serious ischemic events.

Key words:
ADP-receptor blockers, aggregometry, clopidogrel, clopidogrel resistance, diabetes mellitus, phosphorylation VASP, prasugrel, ticagrelor

Received:
30. 12. 2017

Accepted:
29. 1. 2018


Sources

1. Samoš M, Šimonová R, Kovář F et al. Clopidogrel resistance in diabetic patient with acute myocardial infarction due to stent thrombosis. Am J Emerg Med 2014; 32(5): 461–465. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ajem.2014.01.006>.

2. Erlinge D, Varenhorst C, Braun OO et al. Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 2008; 52(24): 1968–1977. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2008.07.068>.

3. Angiolillo DJ, Capranzano P, Desai B et al. Impact of P2Y(12) inhibitory effects induced by clopidogrel on platelet procoagulant activity in type 2 diabetes mellitus patients. Thromb Res 2009; 124(3): 318–322. Dostupné z DOI: <http://dx.doi.org/10.1016/j.thromres.2008.10.001>.

4. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes 2005; 54(3): 2430–2435.

5. Budaj A, Yusuf S, Mehta SR et al. [Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators]. Benefit of clopidogrel in patients with acute coronary syndromes without ST-segment elevation in various risk groups. Circulation 2002; 106(13): 1622–1626.

6. Steinhubl SR, Berger PB, Mann JT et al. [CREDO Investigators. Clopidogrel for the Reduction of Events During Observation]. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 288(19): 2411–2420. Erratum in JAMA 2003 Feb; 289(8): 987.

7. Iakovou I, Schmidt T, Bonizzoni E et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293(17): 2126–2130. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.293.17.2126>.

8. Fedor M, Šimonová R, Fedorová J et al. Role of VASP phosphorylation assay in monitoring the antiplatelet therapy. Acta Med Mart 2013; 13(1): 21–26. Dostupné z DOI: <https://doi.org/10.2478/acm-2013–0008>

9. Samoš M, Fedor M, Kovář F et al. The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study. J Diabetes Res 2016; 2016: 2909436. Dostupné z DOI: <http://dx.doi.org/10.1155/2016/2909436>.

10. Larsen PD, Holley AS, Sasse A et al. Comparison of Multiplate and VerifyNow platelet function tests in predicting clinical outcome in patients with acute coronary syndromes. Thromb Res 2017; 152: 14–19. Dostupné z DOI: <http://dx.doi.org/10.1016/j.thromres.2017.02.006>.

11. Dalby MC, Davidson SJ, Burman JF et al. Diurnal variation in platelet aggregation iwth the PFA-100 platelet function analyser. Platelets 2000; 11(6): 320–324.

12. Mehta SR, Bassand JP, Chrolavicius S et al. [CURRENT-OASIS 7 Investigators]. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010; 363(10): 930–942. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0909475>. Erratum in N Engl J Med 2010; 363(16): 1585.

13. Angiolillo DJ, Shoemaker SB, Desai B et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation 2007; 115(6): 708–716. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.106.667741>.

14. Cui G, Zhang S, Zou J et al. P2Y12 receptor gene polymorphism and the risk of resistance to clopidogrel: A meta-analysis and review of the literature. Adv Clin Exp Med 2017; 26(2): 343–349. Dostupné z DOI: <http://dx.doi.org/10.17219/acem/63745>.

15. Price MJ, Berger PB, Teirstein PS et al. [GRAVITAS Investigators]. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305(11): 1097–1105. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2011.290>. Erratum in JAMA 2011; 305(21); 2174. Stillablower ME.

16. Samoš M, Fedor M, Kovář F et al. Type 2 Diabetes and ADP Receptor Blocker Therapy. J Diabetes Res 2016; 2016: 6760710. Dostupné z DOI: <http://dx.doi.org/10.1155/2016/6760710>.

17. Wiviott SD, Braunwald E, McCabe CH et al. [TRITON-TIMI38 Investigators]. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007(15); 357(20): 2001–2015. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0706482>.

18. Angiolillo DJ, Badimon JJ, Saucedo JF et al. A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial. Eur Heart J 2011; 32(7): 838–846. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehq494>.

19. Samoš M, Fedor M, Kovář F et al. Ticagrelor: a safe and effective approach for overcoming clopidogrel resistance in patients with stent thrombosis? Blood Coagul Fibrinolysis 2016; 27(2): 117–120. Dostupné z DOI: <http://dx.doi.org/10.1097/MBC.0000000000000406>.

20. Wallentin L, Becker RC, Budaj A et al. [PLATO Investigators]. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045–1057. <http://dx.doi.org/10.1056/NEJMoa0904327>.

21. Clavijo LC, Maya J, Carlson G et al. Platelet inhibition with ticagrelor versus clopidogrel in Hispanic patients with stable coronary artery disease with or without diabetes mellitus. Cardiovasc Revasc Med 2015; 16(8): 450–454. <http://dx.doi.org/10.1016/j.carrev.2015.08.007>.

22. Zafar MU, Baber U, Smith DA et al. Antithrombotic potency of ticagrelor versus clopidogrel in type-2 diabetic patients with cardiovascular disease. Thromb Haemost 2017; 117(10): 1981–1988. Dostupné z DOI: <http://dx.doi.org/10.1160/TH17–04–0277>.

23. Mangiacapra F, Panaioli E, Colaiori I et al. Clopidogrel Versus Ticagrelor for Antiplatelet Maintenance in Diabetic Patients Treated With Percutaneous Coronary Intervention: Results of the CLOTILDIA Study (Clopidogrel High Dose Versus Ticagrelor for Antiplatelet Maintenance in Diabetic Patients). Circulation 2016; 134(11): 835–837. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023743>.

24. Franchi F, Rollini F, Aggarwal N et al. Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation 2016; 134(11): 780–792. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023402>.

25. Tan Q, Jiang X, Huang S et al. The clinical efficacy and safety evaluation of ticagrelor for acute coronary syndrome in general ACS patients and diabetic patients: A systematic review and meta-analysis. PLoS One 2017; 12(5): e0177872. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0177872>.

Labels
Angiology Diabetology Internal medicine Cardiology General practitioner for adults
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

×