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Reference: Yao X, Tangri N, Gersh B et al. Renal outcomes in anticoagulated patients with atri.....

Reference: Yao X, Tangri N, Gersh B et al. Renal outcomes in anticoagulated patients with atri.....


JACC 2017;70(21):2621-32

 

KEY MESSAGES:

·         Decline in renal function is commonly observed in patients with atrial fibrillation (AF) treated with anticoagulants

·         The risk of decline is lower in patients treated with dabigatran and rivaroxaban as compared to Vitamin K antagonists (VKA)

·         Dabigatran and Rivaroxaban (but not apixaban) are linked with fewer adverse renal outcomes

·         High INR values are associated with greater degree of nephropathy

INTRODUCTION:

Current guidelines recommend oral anticoagulants for patients with non-valvular AF to prevent stroke.  With the availability of novel oral anticoagulants (NOACs) most of the physicians prefer to treat them with NOACs rather than with VKA if the economics permit. In developing countries it is estimated that approximately 50% patients are treated with NOACs and rest with VKA. Physicians tend to avoid prescribing NOACs in patients with renal dysfunction. Patients with eGFR<30 are prescribed VKA, perceiving it to be less nephrotoxic than NOACs. The comparative risk of renal dysfunction with currently available 3 NOACs versus VKA has not been studied in great detail.

OBJECTIVES:

 To compare the effect of 4 oral anticoagulant agents’ apixaban, dabigatran, rivaroxaban and warfarin on renal functions.

METHODS:

This study included 9769 patients who were treated with oral anticoagulants for prevention of stroke in AF. The average on treatment follow up was 10.7 ± 9.9 months study that evaluated 4 renal parameters:

1.      ≥than 30% decline in eGFR

2.      Rise in serum creatinine by 100%

3.      Acute kidney injury

4.      Kidney failure

The overall risk of adverse kidney outcomes seen at the end of 2 years were-

a)     30% decline in eGFR: 24.4%

b)     Doubling of serum creatinine: 4%

c)      Acute Renal injury: 14.8%

d)     Renal failure: 1.7%

With 3 NOACs combined there was statistically significant reduction in risk of all 4 kidney injury parameters studied as compared to VKA. Individually evaluated dabigatran was associated with lower risk of decline in eGFR and AKI. Rivaroxaban carried a lower risk of fall in eGFR, doubling of creatinine and AKI as compared to VKA.

As compared to rivaroxaban and dabigatran, apixaban did not have significant relationship with decreased adverse renal outcomes when compared to VKA.

CLINICAL RELEVANCE:

Patients with renal failure and AF pose therapeutic challenge since it is perceived that use of NOACs in these patients would lead to extensive bleeding.  Comparative effects of NOACs and warfarin on kidney function were lacking. Patients with AF have several co morbidities like diabetes, hypertension, pre- existing renal dysfunction and coronary artery disease propelling them to further kidney injury. Choice of anticoagulant is therefore of paramount importance.  Warfarin inhibits Vitamin K dependent protein matrix leading to damage to the renal vessels while NOVACs because of their effect on inhibiting factor Xa and thrombin could reduce vascular inflammation. The study further highlights the evidence that very high INR values are associated with greater renal damage.  The therapeutic relevance of the study is that it defies the earlier assumptions of NOVACs being more injurious to kidney as compared to Warfarin. Dabigatran and rivaroxaban could be a better alternative to warfarin to reduce the chances of kidney damage.

 SUGGESTED READINGS

  1. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–51.
  2. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883–91.
  3.  Yao X, Abraham NS, Sangaralingham LR, et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc 2016; 5: e003725.
  4. Böhm M, Ezekowitz MD, Connolly SJ, et al. Changes in renal function in patients with atrial fibrillation: an analysis from the RE-LY Trial. J Am CollCardiol 2015; 65: 2481–93.
  5. Fordyce CB, Hellkamp AS, Lokhnygina Y, et al. On-treatment outcomes in patients with worsening renal function with rivaroxaban compared with warfarin: insights from ROCKET AF. Circulation 2016; 134: 37–47.
  6. Chatrou ML, Winckers K, Hackeng TM, Reutelingsperger CP, Schurgers LJ. Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev 2012; 26: 155–66.
  7. Schurgers LJ, Joosen IA, Laufer EM, et al. Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype. PloS One 2012;7: e43229.
  8. Chan YH, Yeh YH, See LC, et al. Acute kidney injury in Asians with atrial fibrillation treated with dabigatran or warfarin. JACC, 2016;68: 2272–83.

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