Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation

Abstract

Background— Known risk factors for bleeding during anticoagulant treatment are largely the same as those predicting thromboembolic events in patients with atrial fibrillation (AF). Our objective was to investigate how to maximize the likelihood of avoiding both stroke and bleeding. Methods and Results— All 182 678 subjects with atrial fibrillation in the Swedish Hospital Discharge Register were studied for an average of 1.5 years (260 000 patient-years at risk). Patients were stratified according to risk scores with the use of historic International Classification of Disease diagnostic codes in the register. Information about medication was obtained from the Swedish Drug Registry. Our primary end point was net benefit defined as number of avoided ischemic strokes with anticoagulation minus the number of excess intracranial bleedings with a weight of 1.5 to compensate for the generally more severe outcome with intracranial bleedings. The adjusted net clinical benefit favored anticoagulation for almost all atrial fibrillation patients. The exceptions were patients at very low risk of ischemic stroke with a CHA 2 DS 2 -VASc score of 0 and moderately elevated bleeding risk (−1.7%/y). The results were broadly similar with CHADS 2 , except for patients with very low embolic risk; the CHA 2 DS 2 -VASc was able to identify those patients (n=6205, 3.9% of all patients) who had no net clinical benefit or even some disadvantage from anticoagulant treatment. Conclusions— In almost all patients with atrial fibrillation, the risk of ischemic stroke without anticoagulant treatment is higher than the risk of intracranial bleeding with anticoagulant treatment. Analysis of the net benefit indicates that more patients may benefit from anticoagulant treatment.

Safety and Efficacy of Novel Oral Anticoagulants Versus Warfarin in Medicare Beneficiaries With Atrial Fibrillation and Valvular Heart Disease

“…Anticoagulation reduces the thromboembolic risk by approximately two thirds, irrespective of baseline risk 1. However, the use of all antithrombotic agents increased the risk of bleeding, with intracranial hemorrhage being the most serious bleeding complication.…”

Bleeding Risk Scores in Atrial Fibrillation: Helpful or Harmful?

“…The reasons for the lack of clinical impact by bleeding risks scores is partially because of the parallel nature of bleeding risk scores and stroke risk scores such as CHA2DS2‐VASc (Congestive heart failure, Hypertension, Age, Diabetes Mellitus, Prior Stroke, Vascular disease, Sex category) 11. For example, with increasing age, the risk of stroke and major bleeding increase.…”

“…Friberg and colleagues showed that increased thromboembolism risk was associated with increased risk of bleeding, likely because many of the risk factors involved in the risk stratification scores overlap 11. In this study, the only patients who did not benefit from anticoagulation were patients with a CHA2DS2VASc score of 0 or 1, patients in whom anticoagulation is not recommended by either the European Society of Cardiology or AHA/ACC/HRS guidelines 1, 10, 11. In fact, a patient with a CHA2DS2VASc score of 5 and an HAS‐BLED score of 5 would have a net clinical benefit of 3% per year even when weighting intracranial hemorrhage as 1.5 times the clinical impact of a stroke 11.…”

“…In this study, the only patients who did not benefit from anticoagulation were patients with a CHA2DS2VASc score of 0 or 1, patients in whom anticoagulation is not recommended by either the European Society of Cardiology or AHA/ACC/HRS guidelines 1, 10, 11. In fact, a patient with a CHA2DS2VASc score of 5 and an HAS‐BLED score of 5 would have a net clinical benefit of 3% per year even when weighting intracranial hemorrhage as 1.5 times the clinical impact of a stroke 11. In a study by Oleson and colleagues, bleeding risk does increase with higher HAS‐BLED scores 12.…”

“…In recent studies, DOACs have been shown to reduce thromboembolic risk and reduce bleeding risk, most importantly intracranial hemorrhage, in comparison to warfarin 1, 11. These medications have fewer dietary effects and more predictable drug levels without frequent blood draws, providing improved ease of use for patients 1.…”