Ειδικές ομάδες ασθενών με κολπική μαρμαρυγή. Πρέπει,πως και πότε να χορηγηθεί αντιπηκτική αγωγή

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1 11 ΣΥΝΕΔΡΙΟ ΕΠΕΜΒΑΤΙΚΗΣ ΚΑΡΔΙΟΛΟΓΙΑΣ ΚΑΙ ΗΛΕΚΤΡΟΦΥΣΙΟΛΟΓΙΑΣ Ειδικές ομάδες ασθενών με κολπική μαρμαρυγή. Πρέπει,πως και πότε να χορηγηθεί αντιπηκτική αγωγή Χρόνια νεφρική νόσος/αιμοδιύλυση ΣΠΥΡΟΜΗΤΡΟΣ ΓΕΩΡΓΙΟΣ, FESC, E.A, Κ/Δ Γ.Ν.ΚΑΤΕΡΙΝΗΣ

2 European registry analysis reported that up to 60% of atrial fibrillation patients have mild-tomoderate renal dysfunction (egfr ml/min) and up to 4% have severe renal impairment (egfr <30 ml/min). Boriani,Sei.Rep 2016

3 The presence of AF (compared with sinus rhythm) increases the risk of stroke (both ischemic and hemorrhagic) in most but not all series of patients with CKD, and rates between 17 and 24 percent per year have been reported In patients on dialysis with AF, the rate may be as high as 35 percent per year

4 Among patients with AF, CKD is a predictor of stroke, and the risk increases as renal function declines In a study of patients in the Danish national registries, there were 132,372 individuals discharged from a hospital with a diagnosis of AF between 1997 and 2008; 2.7 percent had non-end-stage CKD, and 0.7 percent required renal replacement therapy at the time of inclusion Compared with patients without CKD, the risk of stroke or systemic thromboembolism was increased in both groups (hazard ratios [HRs] 1.49, 95% CI and 1.83, 95% CI , respectively). The ROCKET AF trial the HR for stroke or embolism increased 12 percent for each 10 ml/min decrease in renal function

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6 The issue of whether the development of AF in patients with CKD independently increases the risk of death is difficult to evaluate Patients who have end-stage renal disease (ESRD) and AF have an annual mortality of 5 percent compared with only 2 percent in those without AF

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8 Patients with CKD (particularly those with ESRD receiving hemodialysis), compared with those without, are also at increased risk of bleeding compared with those without, This risk increases as the degree of CKD worsens Limdi,J Am Soc Nephrol. 2009; ESRD on hemodialysis and taking warfarin: The rate of major bleeding ranged from 0.1 to 0.54 events per patientyear of exposure in a systematic review of small studies Warfarin use was associated with a near doubling of the rate of bleeding. Most major bleeding events were gastrointestinal tract bleeding In addition to the usual risk factors for bleeding (age, presence of comorbidities such as cardiovascular or liver disease), poor INR control or monitoring or the concomitant use of aspirin are risk factors for bleeding

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10 Several cohort studies showed that the CHA2DS2-VASc score allows stratification of the embolism risk even in CKD patients The integration of renal function parameters into thecha2ds2-vasc score does not improve its predictive value Banerjee A, Fauchier L, Vourc h P, et al. Renal impairment and ischemic stroke risk assessment in patients with atrial fibrillation: the Loire Valley atrial fibrillation project. J Am Coll Cardiol 2013;

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12 Variability in Non Vitamin K Antagonist Oral Anticoagulants Dose Adjustment in Atrial Fibrillation Patients With Renal Dysfunction The Influence of Renal Function Estimation Formulae 831 AF patients with non-dialysis depentent CKD The use of egfr resulted in significant misclassification with respect to NOAC dosing. Compared with ecrcl, the MDRD egfr and CKD-EPI egfr misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in undertreatment (eg, inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent overtreatment (eg, inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI). August 2018 Volume 34, Can J Cardiology

13 It is a mistake to extrapolate CrCl calculations using creatinine values from acutely ill patients with acute kidney injury. Drug dosing in patients with acute kidney injury should be individualized until the creatinine level stabilizes, which may take weeks or longer

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15 Studies also suggest that patients with advanced CKD and on dialysis require reduced doses of warfarin. This may be in part due to alterations of hepatic metabolism of warfarin secondary to renal failure Animal studies in CKD have shown a significant down-regulation (40% to 85%) of hepatic cytochrome P-450 metabolism, which orroborates with clinical data increased vascular calcification and/or the development of acute warfarin-related nephropathy with or without clinically overt haematuria

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22 Renal function cutoffs varied between trials, with a calculated CrCl of 30 ml/min for dabigatran, <30 ml/min for edoxaban and rivaroxaban, and serum creatinine>2.5 mg/ dl or a calculated CrCl of<25 ml/min for apixaban. All trials excluded patients with severe renal dysfunction The rivaroxaban and edoxaban trials included a larger percentage of patients with diabetes mellitus (40% and 36%,respectively) relative to those for dabigatran (23%) and apixaban (25%), which increases patient risk for bleeding and thrombosis, Larger percentage of patients with heart failure (63% and 57% for rivaroxaban and edoxaban, respectively) relative to dabigatran (32%) and apixaban (35%). Mean patient CHADS2 were highest in the rivaroxaban trial (3.5), followed by edoxaban (2.8), and the apixaban and dabigatran trials (2.1)

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30 14 studies included dialysis patients with AF, of whom (33.5%) were warfarin users.

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35 Increased vascular calcification, either as a direct result of development of ESRD or due to concurrent VKA usage, may potentially increase the likelihood of development of noncardioembolic stroke, which will not be remedied by VKA use. VKA administration has been implicated in development of calciphylaxis, a painful and lethal complication among patients with ESRD, as cutaneous arteries and arterioles undergo calcification and occlusion Galloway PA, El-Damanawi R, Bardsley V,et al. Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease.nephron 2015;129:

36 Chronic kidney disease and arrythmias: The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends against anticoagulation even with warfarin for the prevention of stroke in patients with AF and dialysis-depentent CKD Insufficient high-quality evidence Wanner,Herzog,Turakhia, Conference Steering Committee,Kidney Int.2018 Aug.

37 Dialysis patients with AF and very high-risk predictors for thromboembolism atrial thrombus, valvular/rheumatic heart disease, prosthetic heart valve previous transient ischemic attack or stroke, anticoagulation with warfarin (target INR 2 to 3) The decision to anticoagulate remains a very individualized one requiring a multidisciplinary approach considering and respecting patients preferences Reinecke H, Engelbertz C, Schabitz WR. Preventing stroke in patients with chronic kidney disease and atrial fibrillation: benefit and risks of old and new oral anticoagulants. Stroke 2013;44:

38 Warfarin dosing For patients with AF and an egfr <30 ml/min/1.73 m2 we suggest a target international normalized ratio (INR) of 2 to 3. Reducing the starting dose of warfarin to 2.5 mg daily, based on an increase in the risk of bleeding during the early period of warfarin anticoagulation. INR should be monitored more frequently than usual, particularly during the first 90 days. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. Chan KE, Lazarus JM, Thadhani R, Hakim J Am Soc Nephrol. 2009; Aug 27.

39 Potential alternatives to oral anticoagulants for patients with moderate to severe CKD include parenteral anticoagulants, such as low-molecular-weight heparins, and heparinoids LMWHs have the potential to accumulate in renal failure as they depend on renal elimination and can lead to bleeding complications in patients with CKD 4 5. Certoparin,nadroparin, reviparin, danaparoid, and fondaparinux are not recommended or contraindicated in patients with a GFR <30mL/min Enoxaparin, nadroparin, dalteparin, and tinzaparin may be used with caution and dose adaptation for anticoagulation during HD. International Journal of Nephrology and Renovascular Disease 2017:10

40 Impact of chronic kidney disease on left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation. Kefer J, Tzikas A, Freixa X, Shakir S, Gafoor S, Nielsen-Kudsk JE, Berti S, Santoro G, Aminian A, Landmesser U,Nietlispach F, Ibrahim R, Danna PL, Benit E14, Budts W, Stammen F, De Potter T, Tichelbäcker T, Gloekler S,Kanagaratnam P, Costa M, Cruz- Gonzalez I, Sievert H, Schillinger W, Park JW, Meier B, Omran H CONCLUSION: Patients who are intolerant of warfarin may consider nonpharmacological therapy LAAO for stroke using prevention the ACP has with a percutaneous similar procedural left atrial safety appendage among CKD closure patients compared to patients with normal renal function. LAAO with ACP offers a dramatic reduction of stroke+tia Occlusion of rate the and leftof atrial bleeding appendage rate persistent may be in particularly all stages attractive of CKD, as in compared patients with to the expected ESRD, given annual the risk. observed large reduction in bleeding

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