We thank our correspondents for their comments, which underline our position—that there are not enough data on anticoagulation in chronic kidney disease (CKD) (1). We summarize from a clinical-scientific perspective:
- Data on anticoagulation in advanced CKD and atrial fibrillation are lacking.
- According to prescribing information, phenprocoumon is contraindicated in “manifest renal failure,” but apixaban, edoxaban, and rivaroxaban are licensed for use in patients whose creatinine clearance is 15–30 mL/min.
- Recent studies have shown that vitamin K antagonists (VKA) are associated with vascular calcification processes as a result of an induction of vitamin K deficiency in the vascular wall (2). Such vascular calcifications are common in CKD patients.
- Post hoc analyses of the registration trials show that the relative advantage of NOAC over warfarin (better effectiveness and fewer hemorrhages) in advanced CKD (up to a creatinine clearance of 25–30 mL/min ) is greater than in normal renal function.
- Patients taking VKA are more commonly affected by anticoagulation nephropathy than those taking NOAC, with a deterioration in renal function (4).
- Self-monitoring of VKA treatment by means of INR measurements increases the time period within the therapeutic target range and therapeutic effectiveness, but it does not lower the risk for severe hemorrhages (5).
Clinical research that leads to the use of novel medications costs billions Euros and is therefore only possible with industry funding. Public funding instruments, especially in Germany, are several orders of magnitude lagging behind the necessary investments. What is required is a link between academic science and industry partners, in order to drive medical progress and steer it on to an optimal course. In this scenario, disclosure of possible (!) conflicts of interest is crucial.
We would encourage all those who complain about potential conflicts of interest to participate actively in helping close gaps in the evidence in the sense of optimized patient care.
On behalf of the authors
Prof. Dr. med. Gunnar H. Heine
Saarland University Medical Center, Saarland University Faculty of Medicine, Internal Medicine IV—Nephrology and Hypertension, Homburg
Conflict of interest statement
Prof. Heine has received lecture honoraria from Daiichi Sankyo and honoraria for consultancy services and conference delegate fees from Bristol-Myers Squibb.
|1.||Heine GH, Brandenburg V, Schirmer SH: Oral anticoagulation in chronic kidney disease and atrial fibrillation—the use of non-vitamin K-dependent anticoagulants and vitamin K antagonists. Dtsch Arztebl Int 2018; 115: 287–94 VOLLTEXT|
|2.||Andrews J, Psaltis PJ, Bayturan O, et al.: Warfarin use is associated with progressive coronary arterial calcification: Insights from serial intravascular ultrasound. JACC Cardiovasc Imaging 2017; pii: 1936–878X(17)30477–1.|
|3.||Halvorsen S, Atar D, Yang H, et al.: Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J 2014; 35: 1864–72 CrossRef MEDLINE PubMed Central|
|4.||Chan YH, Yeh YH, Hsieh MY, et al.: 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. Int J Cardiol 2018; 265: 83–9 CrossRef MEDLINE|
|5.||Heneghan CJ, Garcia-Alamino JM, Spencer EA, et al.: Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev 2016; 7: CD003839 CrossRef|