A clinical decision aid for the selection of antithrombotic therapy for the prevention of stroke due to atrial fibrillation

Abstract

Aims: The availability of new antithrombotic agents, each with a unique efficacy and bleeding profile, has introduced a considerable amount of clinical uncertainty with physicians. We have developed a clinical decision aid in order to assist clinicians in determining an optimal antithrombotic regime for the prevention of stroke in patients who are newly diagnosed with non-valvular atrial fibrillation.

Methods and results: The CHA(2)DS(2)-VASc and HAS-BLED scoring systems were used to assess patients' baseline risks of stroke and major bleeding, respectively. The relative risks of stroke and major bleeding for each antithrombotic agent were then used to identify the agent associated with the lowest net risk. Individual patient factors such as the treatment threshold, bleeding ratio, and cost threshold modified the recommendations in order to generate a final recommendation. By considering both patient factors and clinical research concurrently, this clinical decision aid is able to provide specific advice to clinicians regarding an optimal stroke prevention strategy. The resulting treatment recommendation tables are consistent with the recommendations of the European Society of Cardiology and Canadian Cardiovascular Society Guidelines, which can be incorporated into either a paper-based or electronic format to allow clinicians to have decision support at the point of care.

Conclusion: The use of a clinical decision aid that considers both patient factors and evidence-based medicine will serve to bridge the knowledge gap and provide practical guidance to clinicians in the prevention of stroke due to atrial fibrillation.

Figure 1

Annual risks of stroke and bleeding. (A) Annual risk (%/year) of stroke and systemic embolism (SSE) by the CHA₂DS₂-VASc score. Source: Danish National Patient Registry, 10-year follow-up rates. The data used included admission to hospital with or death from thromboembolic events such as ischaemic stroke and peripheral artery embolism. Pulmonary embolism events were excluded. The reported rates were adjusted to account for the use of antiplatelet agents. The decision aid utilizes the adjusted rates shown on the black line to determine patients’ annual risk of SSE with no treatment. (B) Annual risk (%/year) of major bleeding by the HAS-BLED score. Source: Danish National Patient Registry, 1-year incidence. Major bleeding was defined as any bleeding requiring hospitalization and/or causing a decrease in haemoglobin >2 g/L and/or requiring blood transfusion. The decision aid utilizes these values to determine patients’ annual risk of bleeding with no treatment.

Figure 2

Derivation of relative risks of stroke and major bleeding relative to no treatment. (A) Derivation of the risk of stroke relative to no treatment. (B) Derivation of the risk of bleeding relative to no treatment. The values next to the arrows are the relative risk values reported in the relevant study. The relative risk values inside each child box are the product of the parent box and the study relative risk. The relative risk values inside each therapy box are utilized by the decision aid to calculate patients’ risks of stroke and bleeding with treatment.

Figure 3

Validation table for a single cell in the treatment recommendation table. Sample validation table from the website version of the clinical decision aid, which is available for each cell of the treatment recommendation table. This validation table is for the CHA₂DS₂-VASc score = 1, HAS-BLED score = 0 cell of the treatment recommendation table with settings: treatment threshold = 0.5%, bleeding ratio = 2:1, cost threshold = $0.50, and jurisdiction = Ontario, Canada. ARR, absolute risk reduction. Adjusted* net risk, net risk adjusted for a bleeding ratio of 2:1. See the Supplementary material online, Methods and results for details about the calculation of the adjusted net risk. Cost/Benefit^: The daily cost ($) of therapy divided by the absolute risk reduction (%) of stroke. The rows are colour-coded to indicate which do not meet the user-specified criteria. Tan: the medication cost exceeds the cost threshold. Red: the absolute risk reduction of stroke does not meet the treatment threshold.

Figure 4

The treatment recommendation table including new agents. The treatment recommendation table with settings: treatment threshold = 0.5%, bleeding ratio = 2:1, cost threshold = null, and jurisdiction = null. The stroke risk increases from the left to the right along with the CHA₂DS₂-VASc scores at the bottom. The bleeding risk increases from the bottom to the top along with the HAS-BLED scores on the left. The black boxes represent impossible combinations of the stroke and bleed risk due to overlapping risk factors. Apixaban is recommended for a patient with a CHA₂DS₂-VASc score 2 and HAS-BLED score 2.

Figure 5

The treatment recommendation table with therapies available in Canada. The treatment recommendation table with settings: treatment threshold = 0.3%, bleeding ratio = 2:1, cost threshold = $4.00, and jurisdiction = Ontario, Canada. The stroke risk increases from the left to the right along with the CHA₂DS₂-VASc scores at the bottom. The bleeding risk increases from the bottom to the top along with the HAS-BLED scores on the left. The black boxes represent impossible combinations of the stroke and bleed risk due to overlapping risk factors. Acetylsalicylic acid is recommended for a patient with a CHA₂DS₂-VASc score 2 and HAS-BLED score 2. At the time of the writing, the therapies available in Canada are: ASA, clopidogrel, dabigatran 110, dabigatran 150, rivaroxaban, and warfarin. Not available: apixaban.

Figure 6

The treatment recommendation table with the cost threshold = $0.50. The treatment recommendation table with settings: treatment threshold = 0.3%, bleeding ratio = 2:1, cost threshold = $0.50, and jurisdiction = Ontario, Canada. The stroke risk increases from the left to the right along with the CHA₂DS₂-VASc scores at the bottom. The bleeding risk increases from the bottom to the top along with the HAS-BLED scores on the left. The black boxes represent impossible combinations of the stroke and bleed risk due to overlapping risk factors. Acetylsalicylic acid is recommended for a patient with a CHA₂DS₂-VASc score 2 and HAS-BLED score 2.