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Published in:

01-05-2017

Oral antiplatelet drugs in patients with chronic kidney disease (CKD): a review

Authors: Homam Ibrahim, Sunil V. Rao

Published in: Journal of Thrombosis and Thrombolysis | Issue 4/2017

Abstract

Oral Antiplatelet Drugs (OAD) have a proven track record in the risk reduction of major cardiovascular events in patients with cardiovascular disease and normal kidney function. However, major gaps exist in our understanding of their effects on thrombosis and bleeding in chronic kidney disease (CKD). Clinical practice guidelines are ambiguous about use of such drugs in CKD patients, because patients with moderate to severe CKD were systematically excluded from clinical trials evaluating the efficacy and safety of OAD. Paradoxically, CKD patients are at high risk of thrombosis and major bleeding events. Thus, choosing the right combination of OAD for cardiovascular protection in these patients is challenging. Patients with CKD exhibit high rates of OAD hyporesponsiveness. It is, therefore, imperative to explore the mechanisms responsible for poor response to OAD in CKD patients in order to use these drugs more safely and effectively. This review explores suggested mechanisms of platelet dysfucntion in CKD patients and the available evidence on the efficacy and safety of oral antiplatelet drugs in patients with renal dysfunction.

Hoerger TJ et al (2015) The future burden of CKD in the United States: a simulation model for the CDC CKD initiative. Am J Kidney Dis 65(3):403–411CrossRefPubMed

Coresh J et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298(17):2038–2047CrossRefPubMed

Tsai TT et al (2011) Safety and efficacy of drug-eluting stents in older patients with chronic kidney disease: a report from the linked CathPCI Registry-CMS claims database. J Am Coll Cardiol 58(18):1859–1869CrossRefPubMed

Go AS et al (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351(13):1296–1305CrossRefPubMed

Anavekar NS et al (2004) Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 351(13):1285–1295CrossRefPubMed

Rao SV et al (2013) An updated bleeding model to predict the risk of post-procedure bleeding among patients undergoing percutaneous coronary intervention: a report using an expanded bleeding definition from the National Cardiovascular Data Registry CathPCI Registry. JACC Cardiovasc Interv 6(9):897–904CrossRefPubMed

Baber U et al (2015) Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry. Circ Cardiovasc Interv 8(6):e001683CrossRefPubMed

Jain N et al (2013) Antiplatelet therapy in the management of cardiovascular disease in patients with CKD: what is the evidence? Clin J Am Soc Nephrol 8(4):665–674CrossRefPubMed

Levey AS et al (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139(2):137–147CrossRefPubMed

10.

Shlipak MG et al (2002) Cardiovascular disease risk status in elderly persons with renal insufficiency. Kidney Int 62(3):997–1004CrossRefPubMed

11.

Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41CrossRefPubMed

12.

Levey AS et al (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470CrossRefPubMed

13.

Amsterdam EA et al (2014) 2014 AHA/ACC guideline for the management of patients with Non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 64(24):e139–e228CrossRefPubMed

14.

Amsterdam EA et al (2014) 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 130(25):2354–2394CrossRefPubMed

15.

Melloni C et al (2008) Cockcroft-Gault versus modification of diet in renal disease: importance of glomerular filtration rate formula for classification of chronic kidney disease in patients with non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol 51(10):991–996CrossRefPubMed

16.

Boccardo P, Remuzzi G, Galbusera M (2004) Platelet dysfunction in renal failure. Semin Thromb Hemost 30(5):579–589CrossRefPubMed

17.

Gafter U et al (1987) Platelet count and thrombopoietic activity in patients with chronic renal failure. Nephron 45(3):207–210CrossRefPubMed

18.

Linthorst GE et al (2002) Plasma thrombopoietin levels in patients with chronic renal failure. Hematol J 3(1):38–42CrossRefPubMed

19.

Dewanjee MK et al (1994) In vitro and in vivo evaluation of the comparative thrombogenicity of cellulose acetate hemodialyzers with radiolabeled platelets. ASAIO J 40(1):49–55PubMed

20.

Remuzzi G et al (1983) Reduced platelet thromboxane formation in uremia. Evidence for a functional cyclooxygenase defect. J Clin Invest 71(3):762–768CrossRefPubMedPubMedCentral

21.

Di Minno G et al (1985) Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis. Am J Med 79(5):552–559CrossRefPubMed

22.

Mezzano D et al (1996) Hemostatic disorder of uremia: the platelet defect, main determinant of the prolonged bleeding time, is correlated with indices of activation of coagulation and fibrinolysis. Thromb Haemost 76(3):312–321PubMed

23.

Sloand EM et al (1991) Reduction of platelet glycoprotein Ib in uraemia. Br J Haematol 77(3):375–381CrossRefPubMed

24.

Zwaginga JJ et al (1990) High von Willebrand factor concentration compensates a relative adhesion defect in uremic blood. Blood 75(7):1498–1508PubMed

25.

Sreedhara R, Itagaki I, Hakim RM (1996) Uremic patients have decreased shear-induced platelet aggregation mediated by decreased availability of glycoprotein IIb-IIIa receptors. Am J Kidney Dis 27(3):355–364CrossRefPubMed

26.

Ibrahim H et al (2016) Detection and quantification of circulating immature platelets: agreement between flow cytometric and automated detection. J Thromb Thrombolysis 42:77–83CrossRefPubMed

27.

Fager AM et al (2010) Properties of procoagulant platelets: defining and characterizing the subpopulation binding a functional prothrombinase. Arterioscler Thromb Vasc Biol 30(12):2400–2407CrossRefPubMedPubMedCentral

28.

Li Y et al (2010) Levels of main platelet thrombin receptors in older chronic haemodialysis patients. Chin Med J (Engl) 123(17):2495–2496

29.

Li Y et al (2011) Effects of Salivae Miltiorrhizae Liguspyragine Hydrochloride and Glucose Injection on the levels of main platelet thrombin receptors in chronic haemodialysis patients. Chin J Integr Med 17(8):625–630CrossRefPubMed

30.

Feldman HI, Kobrin S, Wasserstein A (1996) Hemodialysis vascular access morbidity. J Am Soc Nephrol 7(4):523–535PubMed

31.

Capodanno D, Angiolillo DJ (2012) Antithrombotic therapy in patients with chronic kidney disease. Circulation 125(21):2649–2661CrossRefPubMed

32.

Polzin A et al (2016) Antiplatelet effects of aspirin in chronic kidney disease patients. J Thromb Haemost 14(2):375–380CrossRefPubMed

33.

Small DS et al (2009) Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease. J Clin Pharm Ther 34(5):585–594CrossRefPubMed

34.

Butler K, Teng R (2012) Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J Clin Pharmacol 52(9):1388–1398CrossRefPubMed

35.

Park SH et al (2009) A comparison of clopidogrel responsiveness in patients with versus without chronic renal failure. Am J Cardiol 104(9):1292–1295CrossRefPubMed

36.

Angiolillo DJ et al (2010) Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J Am Coll Cardiol 55(11):1139–1146CrossRefPubMed

37.

Kosoglou T et al (2012) Pharmacokinetics and pharmacodynamics of the novel PAR-1 antagonist vorapaxar in patients with end-stage renal disease. Eur J Clin Pharmacol 68(7):1049–1056CrossRefPubMed

38.

Schror K (2002) The pharmacology of cilostazol. Diabetes Obes Metab 4(Suppl 2) pp S14–S19CrossRefPubMed

39.

Muller C et al (2012) Association of estimated GFR with platelet inhibition in patients treated with clopidogrel. Am J Kidney Dis 59(6):777–785CrossRefPubMed

40.

Mallikaarjun S, Forbes WP, Bramer SL (1999) Effect of renal impairment on the pharmacokinetics of cilostazol and its metabolites. Clin Pharmacokinet 37(Suppl 2):pp 33–40CrossRefPubMed

41.

Vane JR, Botting RM (2003) The mechanism of action of aspirin. Thromb Res 110(5–6):255–258CrossRefPubMed

42.

Antithrombotic Trialists C et al (2009) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373(9678):1849–1860CrossRef

43.

Jardine MJ et al (2010) Aspirin is beneficial in hypertensive patients with chronic kidney disease: a post-hoc subgroup analysis of a randomized controlled trial. J Am Coll Cardiol 56(12):956–965CrossRefPubMed

44.

Antithrombotic Trialists C (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324(7329):71–86CrossRef

45.

Antiplatelet Trialists’ Collaboration (1994) Collaborative overview of randomised trials of antiplatelet therapy–I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 308(6921):pp 81–106CrossRef

46.

Ethier J et al (2007) Aspirin prescription and outcomes in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 50(4):602–611CrossRefPubMed

47.

McCullough PA et al (2002) Benefits of aspirin and beta-blockade after myocardial infarction in patients with chronic kidney disease. Am Heart J 144(2):226–232CrossRefPubMed

48.

Best PJ et al (2008) The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J 155(4):687–693CrossRefPubMed

49.

Keltai M et al (2007) Renal function and outcomes in acute coronary syndrome: impact of clopidogrel. Eur J Cardiovasc Prev Rehabil 14(2):312–318CrossRefPubMed

50.

Wiviott SD et al (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357(20):2001–2015CrossRefPubMed

51.

Roe MT et al (2012) Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 367(14):1297–1309CrossRefPubMed

52.

James S et al (2010) Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 122(11):1056–1067CrossRefPubMed

53.

Magnani G et al (2015) Efficacy and safety of vorapaxar as approved for clinical use in the United States. J Am Heart Assoc 4(3):e001505CrossRefPubMedPubMedCentral

54.

Morrow DA et al (2012) Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 366(15):1404–1413CrossRefPubMed

55.

Tricoci P et al (2012) Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 366(1):20–33CrossRefPubMed

56.

Lim PS et al (2016) Role of Cilostazol Therapy in Hemodialysis Patients with Asymptomatic Peripheral Arterial Disease: A Retrospective Cohort Study. Biomed Res Int 2016:8236903PubMedPubMedCentral

57.

Bangalore S et al (2014) Efficacy of cilostazol on platelet reactivity and cardiovascular outcomes in patients undergoing percutaneous coronary intervention: insights from a meta-analysis of randomised trials. Open Heart 1(1):e000068CrossRefPubMedPubMedCentral

58.

Park KW et al (2013) Adjunctive cilostazol versus double-dose clopidogrel after drug-eluting stent implantation: the HOST-ASSURE randomized trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety & Effectiveness of Drug-Eluting Stents & Anti-platelet Regimen). JACC Cardiovasc Interv 6(9):932–942CrossRefPubMed

59.

Youn YJ et al (2014) Multicenter randomized trial of 3-month cilostazol use in addition to dual antiplatelet therapy after biolimus-eluting stent implantation for long or multivessel coronary artery disease. Am Heart J p. 241–248(2):e1

60.

Levey AS et al (1998) Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 32(5):853–906CrossRefPubMed

61.

Charytan D, Kuntz RE (2006) The exclusion of patients with chronic kidney disease from clinical trials in coronary artery disease. Kidney Int 70(11):2021–2030CrossRefPubMedPubMedCentral

62.

Price MJ et al (2011) Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305(11):1097–1105CrossRefPubMed

63.

Collet JP et al (2011) Randomized comparison of platelet function monitoring to adjust antiplatelet therapy versus standard of care: rationale and design of the assessment with a double randomization of (1) a fixed dose versus a monitoring-guided dose of aspirin and clopidogrel after DES implantation, and (2) treatment interruption versus continuation, 1 year after stenting (ARCTIC) study. Am Heart J p. 5–12(1):e5CrossRef

64.

Plantinga L et al (2011) Nonsteroidal anti-inflammatory drug use among persons with chronic kidney disease in the United States. Ann Fam Med 9(5):423–430CrossRefPubMedPubMedCentral

65.

Jankovic SM et al (2009) Nonsteroidal antiinflammatory drugs and risk of gastrointestinal bleeding among patients on hemodialysis. J Nephrol 22(4):502–507PubMed

66.

Ibrahim H et al (2014) Association of immature platelets with adverse cardiovascular outcomes. J Am Coll Cardiol 64(20):2122–2129CrossRefPubMed

67.

Eikelboom JW, Warkentin TE (2014) Immature platelet count: part of the cardiologist’s complete blood count? J Am Coll Cardiol 64(20):2130–2132CrossRefPubMed

68.

Bufalino VJ et al (2011) The American Heart Association’s recommendations for expanding the applications of existing and future clinical registries: a policy statement from the American Heart Association. Circulation 123(19):2167–2179CrossRefPubMed

Title: Oral antiplatelet drugs in patients with chronic kidney disease (CKD): a review
Authors: Homam Ibrahim
Sunil V. Rao
Publication date: 01-05-2017
Publisher: Springer US
Published in: Journal of Thrombosis and Thrombolysis / Issue 4/2017
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-017-1483-3

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