Sailing Between Scylla and Charybdis: Oral Long-term Anticoagulation in Dialysis Patients

Thilo Krüger; Vincent Brandenburg; Georg Schlieper; Nikolaus Marx; Jürgen Floege


Nephrol Dial Transplant. 2013;28(3):534-541. 

In This Article

Coumarin Treatment in Dialysis Patients With Atrial Fibrillation

The above considerations illustrate the dilemma of guidelines, which place the vast majority of dialysis patients with atrial fibrillation into a category in need of OAT, but at the same time suggest caution with OATs given their high risk of bleeding. To date, there has not been a single randomized controlled trial on this issue in dialysis patients and all we can use for decision-making are observational data relating to coumarin therapy, i.e. vitamin K antagonists.

An increasing number of studies describe a state of vitamin K deficiency in dialysis patients.[28,29] This may explain why patients with renal disease required an ~20% reduction of their warfarin dose to maintain INR values in the target range. Moreover, these patients had fewer INR measurements within the target range and exhibited an increased risk of over-anticoagulation compared with control patients.[30] Thus, coumarin use is more difficult and potentially prone to more serious adverse effects in advanced CKD when compared with non-renal patients.

An Austrian investigation found that the risk of stroke in dialysis patients increased only non-significantly (2.8-fold) with atrial fibrillation, while the use of anticoagulants [both warfarin and acetylsalicylic acid (ASA)] increased strokes 8.3-fold.[22] Whereas this study is relatively small, three recent large database analyses also assessed the effects of warfarin on dialysis patients with atrial fibrillation:

  • A retrospective analysis of 1671 incident HD patients with preexisting atrial fibrillation investigated the association of ASS or clopidogrel versus warfarin versus no therapy with stroke and death.[31] In a multivariate analysis, the group receiving warfarin exhibited an almost 2-fold higher stroke rate compared with the group without anticoagulation, whereas ASS or clopidogrel patients did not differ from the untreated group. The highest risk of stroke occurred in warfarin patients with no INR monitoring and with the highest INR values. Mortality and hospitalization rates did not differ between the three groups.

  • The DOPPS data from 1996 to 2004 included 2188 patients with prevalent atrial fibrillation. Once again, atrial fibrillation correlated with a higher all-cause mortality and stroke than in the control group. The intake of coumarins increased the risk of stroke in these patients in all age categories, in particular in those over 75 years (HR 2.17, CI 1.04–4.53).[17]

  • Winkelmayer et al. investigated 237 HD patients with incident atrial fibrillation and warfarin treatment. Compared with 948 propensity-matched patients without OAT, there was no difference in the occurrence of ischaemic stroke (HR 0.92; CI 0.61–1.37). In contrast, the risk of haemorrhagic stroke rose 2.38-fold (CI 1.15–4.96) compared with no warfarin treatment.[32]

All the above studies suffer from their retrospective nature, and despite of the different statistical approaches, none can fully exclude confounding by indication, i.e. sicker patients were more likely to receive OAT and more likely to develop strokes.

In contrast to the studies above, others reported benefits of coumarin treatment in HD patients (Table 5). For example, the Austrian trial mentioned above showed that the majority of deaths occurred in the group with atrial fibrillation that did not receive coumarins, and atrial fibrillation patients on coumarins had the second best outcome of all four groups in the study.[24]

The value of coumarins in the patients with less advanced CKD and atrial fibrillation appears to resemble that of non-CKD patients. Thus, patients in CKD stage 3 taking part in the Stroke Prevention of Atrial Fibrillation (SPAF 3) trial were randomly assigned to treatment with warfarin to a target INR of 2.0–3.0 (267 patients) or a fixed low dose of warfarin plus ASA (249 patients). Full-dose warfarin reduced the risk of ischaemic stroke or systemic embolism by 76% compared with the control group in the 2-year treatment period; the rates of major bleeding and death were not significantly different.[33]

The controversy surrounding OAT in dialysis patients with atrial fibrillation is also illustrated by a cost utility analysis of the year 2007, which assessed quality-adjusted life-years depending on the treatment.[34] If the analyses were based on the data from healthy individuals and on the data from Vazquez et al.,[25] OAT therapy resulted in an increase of 0.15 quality-adjusted life-years in HD patients. However, if based on the data of Wiesholzer et al.,[22] a decrease of 1.0 quality-adjusted life-years ensued.

Taken together, the available data do not support a clear benefit of OAT in dialysis patients with atrial fibrillation. Rather, the data stress the practical clinical difficulties when using warfarin or other coumarins in dialysis patients as well as the increased risk in major bleeding episodes.