Chronic warfarin-based anticoagulation is commonly prescribed in the hemodialysis population within the United States and is likely to remain a common treatment in this population in the foreseeable future. In this single-center hemodialysis population, we achieved a relatively low rate of on-target anticoagulation (51%) by instituting a warfarin dosing protocol, and there was no statistically-significant improvement in overall anticoagulation efficacy using a protocol-based dosing method versus a non-standardized provider-based dosing method.
There are several possible explanations for the lack of improved anticoagulation outcomes after the implementation of a protocol-based dosing method as was observed in our study. First, it is possible that our primary outcome measure (time within the therapeutic INR range, TTR) was an inaccurate means to assess the true rate of on-target anticoagulation. This appears unlikely given that measurement of on-target anticoagulation by another statistical methodology—simply the percentage of in-range INR measurements—yields very similar results (50.5% on-target anticoagulation using non-protocolized management, versus 48.4% on-target anticoagulation in the protocol-based management strategy). Second, although nursing adherence to the warfarin protocol was mandated (by dialysis unit policy) throughout the study period, dialysis provider adherence was not. The majority of warfarin dose adjustments were made by nursing staff, but individual provider input was specified per protocol in the extremes of subtherapeutic or supratherapeutic anticoagulation, and decision-making in these “non-standardized” situations may have skewed the overall benefit of protocol-based management. Third, the providers managing warfarin dose adjustments in the pre-protocol timeframe have substantial experience in doing so, and prior research has shown that provider experience in managing warfarin dose adjustments can attenuate the benefit of implementation of a dose adjustment protocol [2].
This study did show a substantial benefit of protocol-based warfarin management in terms of resource utilization, with 30% fewer INR measurements needed to achieve a similar anticoagulation efficacy in the protocol-based management strategy. Further, the use of provider time required for dose adjustment was far less utilizing a protocol rather than reviewing a patient’s prior warfarin dose schedule and determining a new dose in each instance (Additional file 1).
To our knowledge, only one prior study has similarly examined the effect of institution of a warfarin dosing protocol in a hemodialysis population, and this found similar outcomes—no improvement in the rate of therapeutic INR with use of protocol-based dosing, but a reduction in INR measurement utilization with use of a protocol [3] (Additional file 2).
Our study was underpowered to examine the clinical benefit (incidence of thromboembolic stroke, recurrent DVT or PE, etc.…) or clinical harm (bleeding complications) of these two warfarin dosing strategies, however TTR has been validated as a surrogate marker for clinical outcomes in the non-dialysis population [5]. Specifically, prior research has shown that the clinical benefit of anticoagulation in atrial fibrillation (a very common indication for warfarin therapy in the ESRD population) depends very much on achievement of the target INR—with substantially greater benefit in centers achieving TTR >65% versus those who achieve <65% [6]. If the on-target anticoagulation rate in our study is reflective of the typical TTR in the hemodialysis patient population at large it could, in part, explain the large degree of uncertainty as to the overall benefit of warfarin anticoagulation (especially for stroke prevention in atrial fibrillation) in the dialysis population, as compared to the general population [7, 8].