HAS-BLED score as a reference point for risk stratification

Atrial fibrillation (AFib) is a common cardiac arrhythmia and increases the risk of suffering a stroke. According to the current ESC guideline, patients with VHF without a clear contraindication should not be withheld oral anticoagulation. The _CHA2DS2-VASc score can be used to estimate the risk of stroke. The HAS-BLED score has proven useful for risk stratification with regard to bleeding complications. Several recent randomized studies have investigated the situation in patients with device-detected atrial fibrillation.

Atrial fibrillation (AF) is one of the most important risk factors for ischemic cerebrovascular events [1]. The criterion for a clinical VHF is a VHF episode of at least 30 seconds documented in the electrocardiogram (ECG) (box) . AF can be symptomatic or asymptomatic. The prevalence of VHF increases with age. In Europe, 1 in 3 people over the age of 55 will develop an AF over their entire lifetime [2]. Anticoagulation in VHF patients is a tricky subject, admitted Prof. Thorsten Lewalter, MD, Osypka Heart Center Munich [3]. According to the current ESC guideline, there is a clear indication for oral anticoagulation (class IA recommendation) in patients with a _{CHADS2DS2-VASc} score of 2 (men) or 3 (women) [4]. For patients with a low _CHA2DS2-VASc score (score of 0 for men, score of 1 for women), there is currently no indication for permanent anticoagulation [5]. A re-evaluation is advisable after four to six months [4]. The risk of bleeding should also be evaluated before starting oral anticoagulation. If there is a high risk of bleeding (HAS-BLED score >2) but oral anticoagulation is indicated, addressing modifiable risk factors and close monitoring are recommended instead of prophylactic avoidance of oral anticoagulation [4].

Study findings on anticoagulation for device-detected atrial fibrillation

Device-detected atrial fibrillation occurs in around one fifth of all patients with an electronic device implanted in the heart [6]. Several randomized trials investigated the benefits and risks of anticoagulation in patients with transient clinical or non-clinical atrial fibrillation detected by an implanted pacemaker, defibrillator or cardiac monitor.

• Healey et al. 2024 [7]: In this study, 4012 patients (mean age 76.8 ± 7.6 years) with a _CHA2DS2-VASc score ≥3 and ≥1 episode of subclinical AF lasting at least 6 minutes but no longer than 24 hours were identified. The VHF episode was detected by an implanted device. The study participants were randomly assigned to treatment with either apixaban or aspirin. During the average follow-up period of 3.5 years, the incidence of stroke or systemic embolism was significantly lower with apixaban than with aspirin, with 55 and 86 patients** affected respectively (hazard ratio [HR] 0.63; 95% confidence interval [KI], 0.45-0.88; p=0.007). However, the incidence of severe bleeding proved to be significantly higher with apixaban compared to aspirin (1.71 vs. 0.94 per 100 patient-years). The majority of these were gastrointestinal bleedings, but they were quite severe, explained Prof. Lewalter and concluded: “You buy the advantage of stroke prevention with a significant increase in bleeding rates”. The mortality rate was similar in both groups (≈18%).
• Kirchhof et al. 2023 [8]: In the NOAH – AFNET 6 study (Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial High-Rate Episodes), Kirchhof et al. The effects of treatment with the anticoagulant edoxaban (a factor Xa inhibitor) compared with placebo in patients with subclinical AFib (“Atrial High Rate Episodes”, ^AHRE$). The study included patients over 65 years of age who had an AHRE of at least 6 minutes duration and who had at least one additional risk factor for stroke. In those patients in whom AHRE was detected by implantable devices, anticoagulation with edoxaban did not result in a significant reduction in the incidence of cardiovascular mortality, stroke or systemic embolism (combined primary efficacy endpoint) compared to placebo, but did result in a higher incidence of all-cause mortality or major bleeding (safety endpoint). The combined primary efficacy endpoint occurred in 83 of 1270 patients (3.2% per patient-year) in the edoxaban group and in 101 of 1266 patients (4.0% per patient-year) in the placebo group (HR 0.81; 95% CI, 0.60-1.08; p=0.15). “This difference was not statistically significant,” said the speaker [3]. The incidence of strokes was around 1% per patient year in both groups. Major bleeding events and death from any cause occurred in 149 of 1270 patients (5.9% per patient-year) in the edoxaban group and in 114 of 1266 patients (4.5% per patient-year) in the placebo group (HR 1.31; 95% CI, 1.02-1.67; p=0.03). These events were therefore significantly less frequent in the placebo arm.
  

• Becher et al. 2024 [9]: This prespecified secondary analysis of the NOAH-AFNET 6 study investigated how a longer AHRE duration affects the effects of anticoagulation with edoxaban. A total of 259 of the 2389 NOAH-AFNET 6 study participants were included. These were people who had an AHRE ≥24 hours at the start of the study. The mean _CHA2DS2-VASc score was 4, the mean age was 78 ± 7 years, 28% were women. The primary efficacy endpoint was a combination of stroke, systemic embolism or cardiovascular death. The safety endpoint was a composite of major bleeding and all-cause mortality. During a median follow-up period of 1.8 years, the primary endpoint occurred in 9 of 132 patients with an AHRE ≥24 hours (4.3% per patient-year) on anticoagulation and in 14 of 127 patients on placebo (6.9% per patient-year). The AHRE duration had no influence on the efficacy (p-interaction=0.65) or safety (p-interaction=0.98) of anticoagulation. However, patients with an AHRE ≥24 hours developed more ECG-diagnosed atrial fibrillation (17.0% per patient-year) than patients with a shorter AHRE episode (8.2% per patient-year; p<0.001).

** i.e. 0.78 or 1.24 per 100 patient-years
^$ “Atrial High Rate Episodes” is a new entity that corresponds to a subclinical VHF precursor, which may be associated with a slightly increased risk of stroke.

A meta-analysis of NOAH – AFNET 6 confirmed that anticoagulation led to an increase in bleeding complications and a slight reduction in the incidence of ischemic strokes in the relevant study population [10]. Device-detected atrial fibrillation can lead to a stroke, but the risk of stroke appears to be lower than with ECG-documented atrial fibrillation.

Congress: DGK Cardio Update

Literature:

1. “Stroke”, S3 guideline, AWMF register no. 053-011, DEGAM Guideline No. 8, https://register.awmf.org/assets/guidelines/053-011l_S3_Schlaganfall_2023-05.pdf,(last accessed 03.05.2024)
2. Hindricks G, et al: 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42: 373-498.
3. “Supraventricular arrhythmias”, Prof. Dr. med. Thorsten Lewalter, Cardio Update, 23-24.02.2024, Mainz.
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13. Pisters R, et al: A Novel User-Friendly Score (HAS-BLED) To Assess 1-Year Risk of Major Bleeding in Patients With Atrial Fibrillation. Chest 2010; 138(5): 1093-1100.

HAUSARZT PRAXIS 2024; 19(5): 26-27 (published on 25.5.24, ahead of print)