Page 58 - 林口長庚醫研部電子報-2018年9月刊

NEWSLETTER
SEPTEMBER
2018
7 主題：心房顫動患者使用抗凝血藥發生急性腎衰竭
之風險探討
撰稿者 / 校稿者：林口長庚醫院心臟內科詹益欣醫師
論文資訊 : The risk of acute kidney injury in Asians treated with apixaban,rivaroxaban,
dabigatran, or warfarin for non-valvular atrial fibrillation: A nationwide cohort study in
Taiwan
INTERNATIONAL JOURNAL OF CARDIOLOGY, AUG. 2018
IF= 6.189 (12.7%)
第一作者：林口長庚醫院心臟內科詹益欣醫師
指導作者：林口長庚醫院風濕免疫科郭昶甫醫師、林口長庚醫院心臟內科郭啟泰醫師
研究目的背景：
Whether the direct oral anticoagulant (DOAC) is associated with a lower
risk of acute kidney injury (AKI) among patients with non-valvular atrial
fibrillation (NVAF) taking oral anticoagulant remains unknown in real
world.
研究發現與應用：
Oral anticoagulants (OACs), like Vitamin K antagonists (VKAs)
(e.g., warfarin), have been shown to effectively decrease the risk
of thromboembolic events and all-cause mortality in patients with
atrial fibrillation (AF). Meanwhile, OACs can also increase the risk of
hemorrhage due to coagulopathy. Although warfarin has been commonly
used for over 60 years, its harmful effects on renal function, so-called
warfarin-related nephropathy (WRN), have only recently been recognized.
It is estimated that as high as 20.5% of all patients taking warfarin have
experienced at least one episode of WRN during their treatment course,
with most cases occurring within 1 year after the initiation of treatment.
The mechanisms underlying WRN are complicated and multifactorial
but supra-therapeutic doses of warfarin with an International Normalized
Ratio (INR) of > 3.0 may result in glomerular hemorrhage and consequent
tubular injury caused by obstructive tubular RBC casts and heme-induced
free radical injury.
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2018
Warfarin also facilitates renal vascular calcification and the consequent
decline in renal function via inhibition of the activation of matrix
G1a protein and growth arrest specific gene 6 (GAS-6) (Figure 1).
Recently, direct oral anti-coagulants (DOACs), including apixaban,
dabigatran, rivaroxaban, and edoxaban, are increasingly used for the
prevention of ischemic stroke and systemic embolism in non-valvular AF
patients as a safer alternative to warfarin with a lower risk of intracranial
hemorrhage and other causes of major bleeding. DOACs are all excreted
through the kidney in different portions, with around 27% renal excretion
of apixaban and ~80% renal excretion of dabigatran. Recent meta-
analysis showed that the risk of renal failure associated with NOACs
(dabigatran, apixaban, and/or rivaroxaban) was similar to the traditional
anticoagulants including warfarin and low molecular weight heparin
(LMWH).10 Of note, rivaroxaban was associated with an adverse effect
of serum creatinine elevation in some studies. Whether the DOACs with
its anticoagulant mechanism independent from the Vitamin K related
cascade, is associated with a lower risk of acute kidney injury (AKI) in
patients with non-valvular atrial fibrillation (NVAF) remains unknown.
By using the Taiwan nationwide retrospective cohort study, 7,702
and 7,885 NVAF patients without a history of chronic kidney disease
(CKD) and 2,256 and 2,089 NVAF patients with a history of CKD
taking dabigatran and warfarin, respectively, from February 1, 2013 to
December 31, 2013 were analysed. Propensity-score weighted method
was used to balance covariates across study groups. Dabigatran was
associated with a lower risk of AKI comparing with warfarin for either
CKD-free [Hazard ratio (HR):0.62; 95% confidence interval (CI): 0.49-
0.77;P <.001] or CKD cohort [HR:0.56;95% CI: 0.46-0.69;P <.001].As
the increment in CHA2D-VASc score from 0/1 to 6+ points, the annual
incidence of AKI for the dabigatran group was relatively stable (1.87 to
2.91%/year for CKD-free cohort; 7.31% to 13.15%/year for CKD cohort),
but increased obviously for patients taking warfarin for either CKD-free
(2.16 to 6.12%/year) or CKD cohorts (6.82 to 26.03%/year).
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