Top

Published in:

Open Access 01-12-2018 | Opinion

Practical issues in clinical scenarios involving CKD patients requiring antithrombotic therapy in light of the 2017 ESC guideline recommendations

Authors: Adrian Covic, Simonetta Genovesi, Patrick Rossignol, Philip A. Kalra, Alberto Ortiz, Maciej Banach, Alexandru Burlacu

Published in: BMC Medicine | Issue 1/2018

Abstract

Background

The choice of the most appropriate antithrombotic regimen that balances ischemic and bleeding risks was addressed by the August 2017 European Society of Cardiologists (ESC)/European Association for Cardio-Thoracic Surgery Focused Update recommendations, which propose new evaluation scores and protocols for patients requiring a coronary stent or patients with an acute coronary syndrome, atrial fibrillation, or a high bleeding risk and indication for oral anticoagulation therapy.

Discussion

Numerous questions remain regarding antithrombotic regimens and risk management algorithms for both ischemic and hemorrhagic events in patients with chronic kidney disease (CKD) in various clinical scenarios. Limitations of current studies include a general ack of advanced CKD patients in major randomized controlled trials, of evidence on algorithm implementation, and of robust assessment tools for hemorrhagic risk. Herein, we aim to analyze the ESC Update recommendations and the newly implemented risk scores (DAPT, PRECISE-DAPT, PARIS) from the point of view of CKD, providing suggestions on drug choice (which combination has the best evidence), dosage, and duration (the same or different as for non-CKD population) of antithrombotics, as well as to identify current shortcomings and to envision directions of future research.

Conclusion

We provide an evidence-based perspective on the new proposed bleeding management protocol, with focus on the CKD population. Despite previous important steps on antithrombotic therapy of renal patients, there remain many unsolved questions for which our suggestions could fundament new randomized controlled trials and specific protocols.

Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the task force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018;39:213–60.CrossRefPubMed

Valgimigli M, Costa F, Byrne R, Haude M, Baumbach A, Windecker S. Dual antiplatelet therapy duration after coronary stenting in clinical practice: results of an EAPCI survey. EuroIntervention. 2015;11:68–74.CrossRefPubMed

Szummer K, Lundman P, Jacobson SH, Schon S, Lindback J, Stenestrand U, et al. Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome: data from the SWEDEHEART register. J Intern Med. 2010;268:40–9.PubMed

Burlacu A, Genovesi S, Ortiz A, Kanbay M, Rossignol P, Banach M, et al. The quest for equilibrium: exploring the thin red line between bleeding and ischaemic risks in the management of acute coronary syndromes in chronic kidney disease patients. Nephrol Dial Transplant. 2017;32(12):1967–76.CrossRefPubMed

Burlacu A, Genovesi S, Goldsmith D, Rossignol P, Ortiz A, Kalra PA, et al. Bleeding in advanced CKD patients on antithrombotic medication - a critical appraisal. Pharmacol Res. 2018;129:535–43.CrossRefPubMed

Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315:1735–49.CrossRefPubMedPubMedCentral

Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, et al. Coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS. J Am Coll Cardiol. 2016;67:2224–34.CrossRefPubMed

Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389:1025–34.CrossRefPubMed

Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet. 2013;382:614–23.CrossRefPubMed

10.

Polzin A, Dannenberg L, Sansone R, Levkau B, Kelm M, Hohlfeld T, et al. Antiplatelet effects of aspirin in chronic kidney disease patients. J Thromb Haemost. 2016;14:375–80.CrossRefPubMed

11.

Park SH, Kim W, Park CS, Kang WY, Hwang SH, Kim W. A comparison of clopidogrel responsiveness in patients with versus without chronic renal failure. Am J Cardiol. 2009;104:1292–5.CrossRefPubMed

12.

Jeong KH, Cho JH, Woo JS, Kim JB, Kim WS, Lee TW, et al. Platelet reactivity after receiving clopidogrel compared with ticagrelor in patients with kidney failure treated with hemodialysis: a randomized crossover study. Am J Kidney Dis. 2015;65:916–24.CrossRefPubMed

13.

Agewall S, Cattaneo M, Collet JP, Andreotti F, Lip GY, Verheugt FW, et al. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J. 2013;34:1708–13. 1713a–1713bCrossRefPubMed

14.

Moukarbel GV, Bhatt DL. Antiplatelet therapy and proton pump inhibition: clinician update. Circulation. 2012;125:375–80.CrossRefPubMed

15.

Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909–17.CrossRefPubMed

16.

Li L, Geraghty OC, Mehta Z, Rothwell PM. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet. 2017;390(10093):490–9.CrossRefPubMedPubMedCentral

17.

Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176:238–46.CrossRefPubMedPubMedCentral

18.

Arora P, Gupta A, Golzy M, Patel N, Carter RL, Jalal K, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol. 2016;17:112.CrossRefPubMedPubMedCentral

19.

Moledina DG, Perazella MA. PPIs and kidney disease: from AIN to CKD. J Nephrol. 2016;29:611–6.CrossRefPubMed

20.

Brewster UC, Perazella MA. Proton pump inhibitors and the kidney: critical review. Clin Nephrol. 2007;68:65–72.CrossRefPubMed

21.

Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86:837–44.CrossRefPubMedPubMedCentral

22.

Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int. 2017;91:1482–94.CrossRefPubMed

23.

Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. 2016;27:3153–63.CrossRefPubMedPubMedCentral

24.

Alexopoulos D, Xanthopoulou I, Panagiotou A, Komninakis D, Germanos N, Goudas P, et al. Prevalence of inadequate platelet inhibition by clopidogrel in patients receiving hemodialysis. Am J Kidney Dis. 2012;59:469–71.CrossRefPubMed

25.

Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919–33.CrossRefPubMed

26.

Roy-Chaudhury P, Tumlin JA, Koplan BA, Costea AI, Kher V, Williamson D, et al. Primary outcomes of the monitoring in Dialysis study indicate that clinically significant arrhythmias are common in hemodialysis patients and related to dialytic cycle. Kidney Int. 2018;93(4):941–51.CrossRefPubMed

27.

Coritsidis G, Sutariya D, Stern A, Gupta G, Carvounis C, Arora R, et al. Does timing of dialysis in patients with ESRD and acute myocardial infarcts affect morbidity or mortality? Clin J Am Soc Nephrol. 2009;4:1324–30.CrossRefPubMedPubMedCentral

28.

Elliott MJ, Zimmerman D, Holden RM. Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. Am J Kidney Dis. 2007;50:433–40.CrossRefPubMed

29.

Sorensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Andersson C, Jorgensen C, et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet. 2009;374:1967–74.CrossRefPubMed

30.

Lamberts M, Gislason GH, Olesen JB, Kristensen SL, Schjerning Olsen AM, Mikkelsen A, et al. Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention. J Am Coll Cardiol. 2013;62:981–9.CrossRefPubMed

31.

Ishigami J, Grams ME, Naik RP, Coresh J, Matsushita K. Chronic kidney disease and risk for gastrointestinal bleeding in the community: the atherosclerosis risk in communities (ARIC) study. Clin J Am Soc Nephrol. 2016;11:1735–43.CrossRefPubMedPubMedCentral

32.

Ronpichai C, Charat T, Tanyanan T, Wisit K, Pavida P, Wisit C. Safety and efficacy of apixaban versus warfarin in patients with end-stage renal disease: meta-analysis. Pacing Clin Electrophysiol. 2018;41(6):627–34.CrossRef

33.

Turakhia MP, Blankestijn PJ, Carrero JJ, Clase CM, Deo R, Herzog CA, et al. Chronic kidney disease and arrhythmias: conclusions from a kidney disease: improving global outcomes (KDIGO) controversies conference. Eur Heart J. 2018;39(24):2314–25.CrossRefPubMedPubMedCentral

34.

Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107–15.CrossRefPubMed

35.

Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423–34.CrossRefPubMed

36.

Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513–24.CrossRefPubMed

37.

Halvorsen S, Storey RF, Rocca B, Sibbing D, Ten Berg J, Grove EL, et al. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on thrombosis. Eur Heart J. 2017;38:1455–62.PubMed

38.

Yang JY, Lee TC, Montez-Rath ME, Paik J, Chertow GM, Desai M, et al. Trends in acute nonvariceal upper gastrointestinal bleeding in dialysis patients. J Am Soc Nephrol. 2012;23:495–506.CrossRefPubMedPubMedCentral

39.

Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, et al. Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987;76:142–54.CrossRefPubMed

40.

GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673–82.CrossRef

41.

Hansson EC, Jideus L, Aberg B, Bjursten H, Dreifaldt M, Holmgren A, et al. Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study. Eur Heart J. 2016;37:189–97.CrossRefPubMed

42.

Locatelli F, Barany P, Covic A, De Francisco A, Del Vecchio L, Goldsmith D, et al. Kidney disease: improving global outcomes guidelines on anaemia management in chronic kidney disease: a European renal best practice position statement. Nephrol Dial Transplant. 2013;28:1346–59.CrossRefPubMed

43.

Kaw D, Malhotra D. Platelet dysfunction and end-stage renal disease. Semin Dial. 2006;19:317–22.CrossRefPubMed

44.

Svensson PJ, Bergqvist PB, Juul KV, Berntorp E. Desmopressin in treatment of haematological disorders and in prevention of surgical bleeding. Blood Rev. 2014;28:95–102.CrossRefPubMed

45.

Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706–17.CrossRefPubMed

46.

Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.CrossRefPubMed

47.

Roe MT, Armstrong PW, Fox KA, White HD, Prabhakaran D, Goodman SG, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297–309.CrossRefPubMed

48.

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–57.CrossRefPubMed

49.

Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.CrossRefPubMed

50.

Bonaca MP, Bhatt DL, Steg PG, Storey RF, Cohen M, Im K, et al. Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54. Eur Heart J. 2016;37:1133–42.CrossRefPubMed

51.

Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155–66.CrossRefPubMedPubMedCentral

52.

Palmerini T, Benedetto U, Bacchi-Reggiani L, Della Riva D, Biondi-Zoccai G, Feres F, et al. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet. 2015;385:2371–82.CrossRefPubMed

53.

Navarese EP, Andreotti F, Schulze V, Kolodziejczak M, Buffon A, Brouwer M, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015;350:h1618.CrossRefPubMedPubMedCentral

54.

Giustino G, Baber U, Sartori S, Mehran R, Mastoris I, Kini AS, et al. Duration of dual antiplatelet therapy after drug-eluting stent implantation: a systematic review and meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2015;65:1298–310.CrossRefPubMed

55.

Kim BK, Hong MK, Shin DH, Nam CM, Kim JS, Ko YG, et al. A new strategy for discontinuation of dual antiplatelet therapy: the RESET trial (REal safety and efficacy of 3-month dual antiplatelet therapy following endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol. 2012;60:1340–8.CrossRefPubMed

56.

Feres F, Costa RA, Abizaid A, Leon MB, Marin-Neto JA, Botelho RV, et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310:2510–22.PubMed

57.

Urban P, Meredith IT, Abizaid A, Pocock SJ, Carrie D, Naber C, et al. Polymer-free drug-coated coronary stents in patients at high bleeding risk. N Engl J Med. 2015;373:2038–47.CrossRefPubMed

58.

Valgimigli M, Patialiakas A, Thury A, McFadden E, Colangelo S, Campo G, et al. Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates. J Am Coll Cardiol. 2015;65:805–15.CrossRefPubMed

59.

Hermiller JB, Krucoff MW, Kereiakes DJ, Windecker S, Steg PG, Yeh RW, et al. Benefits and risks of extended dual antiplatelet therapy after everolimus-eluting stents. JACC Cardiovasc Interv. 2016;9:138–47.CrossRefPubMed

60.

Costa F, Adamo M, Ariotti S, Navarese EP, Biondi-Zoccai G, Valgimigli M. Impact of greater than 12-month dual antiplatelet therapy duration on mortality: drug-specific or a class-effect? A meta-analysis. Int J Cardiol. 2015;201:179–81.CrossRefPubMed

61.

Costa F, Tijssen JG, Ariotti S, Giatti S, Moscarella E, Guastaroba P, et al. Incremental value of the CRUSADE, ACUITY, and HAS-BLED risk scores for the prediction of hemorrhagic events after coronary stent implantation in patients undergoing long or short duration of dual antiplatelet therapy. J Am Heart Assoc. 2015;4(12):e002524.PubMedPubMedCentralCrossRef

62.

Palmerini T, Della Riva D, Benedetto U, Bacchi Reggiani L, Feres F, Abizaid A, et al. Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. Eur Heart J. 2017;38:1034–43.PubMedPubMedCentral

63.

Cassese S, Byrne RA, Ndrepepa G, Kufner S, Wiebe J, Repp J, et al. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387:537–44.CrossRefPubMed

64.

Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrie D, Piek JJ, et al. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388:2479–91.CrossRefPubMed

65.

Raber L, Brugaletta S, Yamaji K, O’Sullivan CJ, Otsuki S, Koppara T, et al. Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol. 2015;66:1901–14.CrossRefPubMed

66.

Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation. 2011;123:2736–47.CrossRefPubMed

Title: Practical issues in clinical scenarios involving CKD patients requiring antithrombotic therapy in light of the 2017 ESC guideline recommendations
Authors: Adrian Covic
Simonetta Genovesi
Patrick Rossignol
Philip A. Kalra
Alberto Ortiz
Maciej Banach
Alexandru Burlacu
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2018
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-018-1145-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Practical issues in clinical scenarios involving CKD patients requiring antithrombotic therapy in light of the 2017 ESC guideline recommendations

Abstract

Background

Discussion

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Discussion

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2018

A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions

Zika vaccines and therapeutics: landscape analysis and challenges ahead

Impact of preventive primary care on children’s unplanned hospital admissions: a population-based birth cohort study of UK children 2000–2013

Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

Migration and tuberculosis transmission in a middle-income country: a cross-sectional study in a central area of São Paulo, Brazil

Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children