Atrial fibrillation decision support tool: Population perspective

Abstract

Background: Appropriate thromboprophylaxis for patients with atrial fibrillation or atrial flutter (AF) remains a national challenge. The recent availability of direct oral anticoagulants (DOACs) with comparable efficacy and improved safety compared with warfarin alters the balance between risk factors for stroke and benefit of anticoagulation. Our objective was to examine the impact of DOACs as an alternative to warfarin on the net benefit of oral anticoagulant therapy (OAT) in a real-world population of AF patients.

Methods: This is a retrospective cohort study of patients with paroxysmal or persistent nonvalvular AF. We updated an Atrial Fibrillation Decision Support Tool (AFDST) to include DOACs as treatment options. The tool generates patient-specific recommendations based upon individual patient risk factor profiles for stroke and major bleeding using quality-adjusted life-years (QALYs) calculated for each treatment strategy by a decision analytic model. The setting included inpatient and ambulatory sites in an academic health center in the midwestern United States. The study involved 5,121 adults with nonvalvular AF seen for any ambulatory visit or inpatient hospitalization over the 1-year period (January through December 2016). Outcome measure was net clinical benefit in QALYs.

Results: When DOACs are a therapeutic option, the AFDST recommends OAT for 4,134 (81%) patients and no antithrombotic therapy or aspirin for 489 (9%). A strong recommendation for OAT could not be made in 498 (10%) patients. When warfarin is the only option, OAT is recommended for 3,228 (63%) patients and no antithrombotic therapy or aspirin for 973 (19%). A strong recommendation for OAT could not be made in 920 (18%) patients. In total, 1,508 QALYs could be gained if treatment were changed to that recommended by the AFDST.

Conclusions: Availability of DOACs increases the proportion of patients for whom oral anticoagulation therapy is recommended in a real-world cohort of AF patients and increased projected QALYs by more than 1,500 when all patients are receiving thromboprophylaxis as recommended by the AFDST compared with current treatment.

Figure 1

Sample Report from AFDST. Screen shot of report that appears in Epic Hyperspace frame when AFDSM is launched from a patient’s chart. Red, bolded items indicate clinical risk factors extracted from the AF data-mart used to predict the patient’s risk of stroke, major bleeding, intracranial bleeding and QALYs for each of the considered treatments. In this example, the patient is an 80-year old woman with a history of hypertension and type II diabetes. Her most recent estimated glomerular filtration rate (eGFR) is 70 mm/min/1.73m². Her HAS-BLED is one and her CHA₂DS₂VASc score is five. Her annual rate of ischemic stroke without thromboprophylaxis is 6.7%. Her annual rate of major non-CNS bleeding while taking warfarin is 0.7%. This is an upper limit on risk of major bleeding, as the relative hazard of major bleeding is less than one for several of the DOACs. A separate model predicts the annual rate of intracerebral hemorrhage (ICH) while taking warfarin, 0.29% for this patient. This also is an upper limit, as the relative hazard of ICH is less than one for all of the DOACs. The graphic to the far right indicates gain or loss in QALYs for each of the considered strategies compared with no treatment. The visual analog scale is divided into three regions – green, indicating a clinically significant gain; red, indicating a clinically significant loss; and yellow, indicating a gain or loss less than 0.1 QALYs, which makes treatment too close to call as a recommended strategy compared with no treatment. For this patient, aspirin provides no benefit, while warfarin and the four DOACs all fall in the green range, providing net gains of 0.72 to 0.97 QALYs compared with no treatment. In particular, dabigatran, apixaban, and edoxaban all fall within 0.1 QALYs of each other, making them indistinguishable from a decision analytic perspective. In this example, all of the oral anticoagulants are reasonable choices. The patient’s decision between these agents needs to be guided by other more nuanced factors such as out-of-pocket cost, availability of reversal agent, number of doses per day, need for routine laboratory testing, etc. The clinician can click on the tab labelled “Print” to give the patient a copy of the report to take home. To facilitate this discussion in a typical shared decision-making encounter, the clinician would next click on the tab at the far right of the top ribbon, labeled “Anticoagulant Medication Details.” A graphic of medication cards (see appendix figure 2) detailing these factors that are important for patient choices between the various recommended oral anticoagulants appears, continuing to support the shared decision-making discussion.

Figure 2

AFDST-Recommended-treatment compared with current treatment. Panel A – results of AF cohort analysis when DOACs are available options for oral anticoagulant therapy. Recommendations and current treatment are concordant along the diagonal from the top left to the bottom right of the figure. In the discordant cells (bottom left to top right), the lower number represents the gain or loss in QALYs between recommended and current treatment. For instance, (bottom left), 119 QALYs could be gained were the 123 patients currently receiving treatment with oral anticoagulant therapy for whom the AFDST recommended either no thromboprophylaxis or aspirin, taken off oral anticoagulants. In the cell at the top right, 1,362 QALYs could be gained if these 1,673 patients currently not receiving oral anticoagulant therapy, were started on such treatment. In the setting of DOAC availability, an aggregate gain of 1,481 QALYs could potentially be achieved were treatment changed to that recommended by the AFDST. Panel B – results of AF cohort analysis when warfarin is the only available option for oral anticoagulant therapy. In this setting, an aggregate gain of 872 QALYs could potentially be achieved were treatment changed to that recommended by the AFDST.

Figure 2

AFDST-Recommended-treatment compared with current treatment. Panel A – results of AF cohort analysis when DOACs are available options for oral anticoagulant therapy. Recommendations and current treatment are concordant along the diagonal from the top left to the bottom right of the figure. In the discordant cells (bottom left to top right), the lower number represents the gain or loss in QALYs between recommended and current treatment. For instance, (bottom left), 119 QALYs could be gained were the 123 patients currently receiving treatment with oral anticoagulant therapy for whom the AFDST recommended either no thromboprophylaxis or aspirin, taken off oral anticoagulants. In the cell at the top right, 1,362 QALYs could be gained if these 1,673 patients currently not receiving oral anticoagulant therapy, were started on such treatment. In the setting of DOAC availability, an aggregate gain of 1,481 QALYs could potentially be achieved were treatment changed to that recommended by the AFDST. Panel B – results of AF cohort analysis when warfarin is the only available option for oral anticoagulant therapy. In this setting, an aggregate gain of 872 QALYs could potentially be achieved were treatment changed to that recommended by the AFDST.

Figure 3

Heatmap showing gain or loss in QALYs for the UC Health AF cohort stratified by CHA₂DS₂VASc and HAS-BLED scores. More intense red colors correspond to regions of larger gain, while lighter blue colors correspond to regions of lesser gain. All gains or losses in both panels are relative to no thromboprophylaxis. Panel A – results when DOACs are available options for anticoagulant therapy. Largest gains are within the region where CHA₂DS₂VASc scores are between one and five and HAS-BLED scores are between zero and three. Panel B – results when warfarin is the only available option for oral anticoagulant therapy. Region of large population gains is smaller than in panel A, when DOACs are available. Largest gains are within the smaller region where CHA₂DS₂VASc scores are between one and four and HAS-BLED scores are between zero and two. In addition, the magnitude of the gains in even the most optimistic cells is smaller than in panel A.