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A Narrative Review on Thrombolytics in Advanced CKD: Is it an Evidence-Based Therapy?

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Abstract

Purpose

A timely pharmacoinvasive strategy consisting of thrombolytic therapy (TT) plays a pivotal role in three major scenarios: acute ischemic stroke (AIS), acute myocardial infarction (STEMI), and massive pulmonary embolism (PE). Presence of advanced chronic kidney disease (CKD) (estimated glomerular filtration rate < 30 mL/min/1.73 m2), known to disturb thrombotic/thrombolytic equilibrium, causes difficulties for clinicians in evaluating risk-benefit balance, as current guidelines do not address the relationship between TT and the advanced CKD. This narrative review aims to evaluate the most important scientific resources regarding the evidences, benefits, and risks of using thrombolytics in advanced CKD.

Methods

We searched the electronic database of PubMed for studies evaluating the relationship between renal dysfunction and TT in patients with STEMI, AIS, and massive PE. Randomized controlled trials (RCTs), observational studies including prospective or retrospective cohort studies, reviews, meta-analyses, and guidelines were included if referring to TT for one of the three scenarios in advanced CKD.

Results

Prothrombotic conditions in CKD, associated with an increased risk of hemorrhages, can affect the safety and efficacy of TT. Concerns regarding in-hospital bleeding events and poor clinical outcomes subsequent to TT in advanced CKD continue to cause underutilization or delaying routine reperfusion therapy.

Conclusions

The impact of TT on the outcomes of advanced CKD patients is poorly understood to date, with scarce data available in current guidelines and conflicting results from observational studies. Until evidence-based data from RCTs will be obtained, the clinical challenge of maximizing benefits for this high-risk subgroup lays in the hands of practicing clinicians.

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References

  1. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119–77.

    Article  Google Scholar 

  2. Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619.

    Article  Google Scholar 

  3. Bivard A, Lin L, Parsonsb MW. Review of stroke thrombolytics. J Stroke. 2013;15(2):90–8.

    Article  Google Scholar 

  4. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, et al. ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033–69. 69a-69k

    Article  CAS  Google Scholar 

  5. Patel B, Sablani N, Shah M, Garg L, Agarwal M, Agrawal S, et al. Evaluating safety of thrombolysis in chronic kidney disease patients presenting with pulmonary embolism using propensity score matching. J Thromb Thrombolysis. 2017;44(3):324–9.

    Article  Google Scholar 

  6. Agrawal V, Rai B, Fellows J, McCullough PA. In-hospital outcomes with thrombolytic therapy in patients with renal dysfunction presenting with acute ischaemic stroke. Nephrol Dial Transplant. 2010;25(4):1150–7.

    Article  Google Scholar 

  7. Sharma S, Farrington K, Kozarski R, Christopoulos C, Niespialowska-Steuden M, Moffat D, et al. Impaired thrombolysis: a novel cardiovascular risk factor in end-stage renal disease. Eur Heart J. 2013;34(5):354–63.

    Article  CAS  Google Scholar 

  8. Abraham P, Arroyo DA, Giraud R, Bounameaux H, Bendjelid K. Understanding haemorrhagic risk following thrombolytic therapy in patients with intermediate-risk and high-risk pulmonary embolism: a hypothesis paper. Open Heart. 2018;5(1):e000735.

    Article  Google Scholar 

  9. Hassine M, Cheniti G, Selmi W, Ben Massoud M, Dridi Z, Betbout F, et al. Reperfusion strategy for patients with renal dysfunction presenting with STEMI: which is better in the North African context? Acta Cardiol. 2014;69(3):245–51.

    Article  Google Scholar 

  10. Russo JJ, Goodman SG, Cantor WJ, Ko DT, Bagai A, Tan MK, et al. Does renal function affect the efficacy or safety of a pharmacoinvasive strategy in patients with ST-elevation myocardial infarction? A meta-analysis. Am Heart J. 2017;193:46–54.

    Article  Google Scholar 

  11. Coca SG, Krumholz HM, Garg AX, Parikh CR. Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease. JAMA. 2006;296(11):1377–84.

    Article  CAS  Google Scholar 

  12. Power A, Fogarty D, Wheeler DC. Acute stroke thrombolysis in end-stage renal disease: a national survey of nephrologist opinion. Nephron Clin Pract. 2013;124(3–4):167–72.

    Article  CAS  Google Scholar 

  13. Palacio S, Gonzales NR, Sangha NS, Birnbaum LA, Hart RG. Thrombolysis for acute stroke in hemodialysis: international survey of expert opinion. Clin J Am Soc Nephrol: CJASN. 2011;6(5):1089–93.

    Article  Google Scholar 

  14. Chao TH, Lin TC, Shieh Y, Chang TY, Hung KL, Liu CH, et al. Intracerebral hemorrhage after thrombolytic therapy in acute ischemic stroke patients with renal dysfunction. Eur Neurol. 2013;70(5–6):316–21.

    Article  CAS  Google Scholar 

  15. Shah HH, Chow AO, Mattana J. Stroke in patients undergoing dialysis. Int J Artif Organs. 2000;23(2):77–82.

    Article  CAS  Google Scholar 

  16. Committee ESOE, Committee EW. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457–507.

    Article  Google Scholar 

  17. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–e110.

    Article  Google Scholar 

  18. Wein T, Lindsay MP, Cote R, Foley N, Berlingieri J, Bhogal S, et al. Canadian stroke best practice recommendations: secondary prevention of stroke, sixth edition practice guidelines, update 2017. Int J Stroke. 2018;13(4):420–43.

    Article  Google Scholar 

  19. Foundation S. Clinical guidelines for stroke management 2017.2017.

  20. Rudd AG, Bowen A, Young GR, James MA. The latest national clinical guideline for stroke. Clin Med (Lond, Engl). 2017;17(2):154–5.

    Article  Google Scholar 

  21. Jalal DI, Chonchol M, Targher G. Disorders of hemostasis associated with chronic kidney disease. Semin Thromb Hemost. 2010;36(1):34–40.

    Article  CAS  Google Scholar 

  22. Toyoda K, Ninomiya T. Stroke and cerebrovascular diseases in patients with chronic kidney disease. Lancet Neurol. 2014;13(8):823–33.

    Article  Google Scholar 

  23. Pantoni L, Fierini F, Poggesi A. Thrombolysis in acute stroke patients with cerebral small vessel disease. Cerebrovasc Dis (Basel, Switzerland). 2014;37(1):5–13.

    Article  CAS  Google Scholar 

  24. Jung JM, Kim HJ, Ahn H, Ahn IM, Do Y, Choi JY, et al. Chronic kidney disease and intravenous thrombolysis in acute stroke: a systematic review and meta-analysis. J Neurol Sci. 2015;358(1–2):345–50.

    Article  Google Scholar 

  25. Hirano T. Thrombolysis and hyperacute reperfusion therapy for stroke in renal patients. Brain, stroke and kidney. Karger Publishers; 2013. p. 110–8.

  26. Gensicke H, Zinkstok SM, Roos YB, Seiffge DJ, Ringleb P, Artto V, et al. IV thrombolysis and renal function. Neurology. 2013;81(20):1780–8.

    Article  CAS  Google Scholar 

  27. Hao Z, Yang C, Liu M, Wu B. Renal dysfunction and thrombolytic therapy in patients with acute ischemic stroke: a systematic review and meta-analysis. Medicine. 2014;93(28):e286.

    Article  CAS  Google Scholar 

  28. Carr SJ, Wang X, Olavarria VV, Lavados PM, Rodriguez JA, Kim JS, et al. Influence of renal impairment on outcome for thrombolysis-treated acute ischemic stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) post hoc analysis. Stroke. 2017;48(9):2605–9.

    Article  Google Scholar 

  29. Hirano T. Thrombolysis and hyperacute reperfusion therapy for stroke in renal patients. Contrib Nephrol. 2013;179:110–8.

    Article  Google Scholar 

  30. Bayley M, Lindsay P, Hellings C, Woodbury E, Phillips S. Balancing evidence and opinion in stroke care: the 2008 best practice recommendations. CMAJ. 2008;179(12):1247–9.

    Article  Google Scholar 

  31. Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581–641.

    Article  Google Scholar 

  32. 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(1):40–9.

    CAS  PubMed  Google Scholar 

  33. Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285–95.

    Article  CAS  Google Scholar 

  34. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305.

    Article  CAS  Google Scholar 

  35. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, et al. ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012;61(23):e179–347.

    Article  Google Scholar 

  36. Herzog CA. Acute myocardial infarction in patients with end-stage renal disease. Kidney Int Suppl. 1999;71:S130–3.

    Article  CAS  Google Scholar 

  37. Chew DP, Scott IA, Cullen L, French JK, Briffa TG, Tideman PA, et al. National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of acute coronary syndromes 2016. Heart Lung Circ. 2016;25(9):895–951.

    Article  Google Scholar 

  38. O'gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, De Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(4):485–510.

    Article  Google Scholar 

  39. National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance. Myocardial infarction with ST-segment elevation: the acute management of myocardial infarction with ST-segment elevation. London: Royal College of Physicians (UK) National Clinical Guideline Centre.; 2013.

  40. Fitchett DH, Theroux P, Brophy JM, Cantor WJ, Cox JL, Gupta M, et al. Assessment and management of acute coronary syndromes (ACS): a Canadian perspective on current guideline-recommended treatment—part 2: ST-segment elevation myocardial infarction. Can J Cardiol. 2011;27(Suppl A):S402–12.

    Article  Google Scholar 

  41. Gibson CM, Pinto DS, Murphy SA, Morrow DA, Hobbach HP, Wiviott SD, et al. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality. J Am Coll Cardiol. 2003;42(9):1535–43.

    Article  CAS  Google Scholar 

  42. Cannon CP, McCabe CH, Gibson CM, Ghali M, Sequeira RF, McKendall GR, et al. TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation. 1997;95(2):351–6.

    Article  CAS  Google Scholar 

  43. Cannon CP, Gibson CM, McCabe CH, Adgey AA, Schweiger MJ, Sequeira RF, et al. TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators. Circulation. 1998;98(25):2805–14.

    Article  CAS  Google Scholar 

  44. Antman EM, Gibson CM, de Lemos JA, Giugliano RP, McCabe CH, Coussement P, et al. Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. The Thrombolysis in Myocardial Infarction (TIMI) 14 Investigators. Eur Heart J. 2000;21(23):1944–53.

    Article  CAS  Google Scholar 

  45. InTIME-II Investigators. Intravenous NPA for the treatment of infarcting myocardium early; InTIME-II, a double-blind comparison of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction. Eur Heart J. 2000;21(24):2005–13.

    Article  Google Scholar 

  46. Newsome BB, Warnock DG, Kiefe CI, Weissman NW, Houston TK, Centor RM, et al. Delay in time to receipt of thrombolytic medication among Medicare patients with kidney disease. Am J Kidney Dis. 2005;46(4):595–602.

    Article  CAS  Google Scholar 

  47. Roberts JK, McCullough PA. The management of acute coronary syndromes in patients with chronic kidney disease. Adv Chronic Kidney Dis. 2014;21(6):472–9.

    Article  Google Scholar 

  48. Santopinto JJ, Fox KA, Goldberg RJ, Budaj A, Pinero G, Avezum A, et al. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE). Heart. 2003;89(9):1003–8.

    Article  CAS  Google Scholar 

  49. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008;29(23):2909–45.

    Article  Google Scholar 

  50. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569–619.

    Article  CAS  Google Scholar 

  51. Capodanno D, Angiolillo DJ. Antithrombotic therapy in patients with chronic kidney disease. Circulation. 2012;125(21):2649–61.

    Article  Google Scholar 

  52. Kumar G, Sakhuja A, Taneja A, Majumdar T, Patel J, Whittle J, et al. Pulmonary embolism in patients with CKD and ESRD. Clin J Am Soc Nephrol: CJASN. 2012;7(10):1584–90.

    Article  Google Scholar 

  53. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788–830.

    Article  Google Scholar 

  54. Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of pulmonary embolism: an update. J Am Coll Cardiol. 2016;67(8):976–90.

    Article  Google Scholar 

  55. Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” trial). Am J Cardiol. 2013;111(2):273–7.

    Article  Google Scholar 

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Correspondence to Bogdan Artene.

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Given the fact that this study is a narrative review, there was no need to obtain an informed consent.

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Burlacu, A., Artene, B. & Covic, A. A Narrative Review on Thrombolytics in Advanced CKD: Is it an Evidence-Based Therapy?. Cardiovasc Drugs Ther 32, 463–475 (2018). https://doi.org/10.1007/s10557-018-6824-8

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