Anticoagulation of little benefit to patients with device-detected AF, multiple comorbidities

Giving oral anticoagulants to patients with device-detected atrial fibrillation (AF) and multiple comorbidities does not necessarily help lower the rate of cardiovascular events, according to a subgroup analysis of the NOAH-AFNET 6 trial.

In the subgroup of patients with a CHA₂DS₂-VASc score of >4, the incidence of the efficacy outcome—defined as a composite of stroke, systemic embolism, or cardiovascular death—was comparable between those who received edoxaban and those who received placebo (4.6 vs 5.3 per 100 patient-years; hazard ratio [HR], 0.88, 95 percent confidence interval [CI], 0.55–1.41). [Eur Heart J 2024;doi:10.1093/eurheartj/ehae225]

Specifically, the rate of ischaemic stroke was low and likewise similar between the edoxaban and placebo groups (1.2 vs 1.3 per 100 patient-years), reported one of the study authors Dr Julius Nikorowitsch of University Medical Center Hamburg-Eppendorf (UKE) in Hamburg, Germany, who presented the results at EHRA 2024.

In terms of the primary safety outcome, however, edoxaban was associated with higher rates of major bleeding or death (8.7 vs 5.6 per 100 person-years; HR, 1.59, 95 percent CI, 1.06–2.39).

Risk factors for the efficacy outcome included older age (per 10-year increase: HR, 1.73, 95 percent CI, 1.35–2.22), diabetes (HR, 1.66, 95 percent CI, 1.19–2.30), and estimated glomerular filtration rate (eGFR; per 10 mL/min/1.73 m² decrease: HR, 1.16, 95 percent CI, 1.06–1.27).

Meanwhile, the safety outcome was independently predicted by anticoagulation (HR, 1.31, 95 percent CI, 1.02–1.69), age (per 10-year increase: HR, 1.92, 95 percent CI, 1.56–2.36), heart failure (HR, 1.53, 95 percent CI, 1.16–2.02), diabetes (HR, 1.67, 95 percent CI, 1.26–2.19), prior stroke (HR, 1.50, 95 percent CI, 1.05–2.13), and eGFR (per 10 mL/min/1.73 m² decrease: HR, 1.12, 95 percent CI, 1.04–1.21).

In the total population (CHA₂DS₂-VASc score of >4 and ≤4), the rates of efficacy and safety events increased progressively with CHA₂DS₂-VASc scores, without any treatment interactions observed. The findings were robust to sensitivity analyses.

“We were interested if oral anticoagulation might reduce cardiovascular event rates in patients with a high burden of these factors and device-detected AF,” Nikorowitsch said. “And this prespecified subanalysis of NOAH-AFNET 6 does not suggest that anticoagulation is more effective in patients with device-detected AF and a high CHA₂DS₂-VASc score >4.”

According to Nikorowitsch, the low rate of stroke and the weak effect of anticoagulation observed here and in a previous meta-analysis could be due to several reasons. First and foremost is the improved management of other health problems in this population, in light of the availability of more effective therapies for diabetes, heart failure, and hypertension. [Circulation 2024;149:981-988]

Also, careful and frequent (every 6 months) ECG assessment for AF, combined with the implementation of guideline-directed open-label anticoagulation therapy, and the inherently low arrhythmia burden in patients with device-detected AF, as reported in other studies, all likely contributed to the low stroke rate observed in this cohort, Nikorwitsch continued. [J Am Coll Cardiol 2019;74:2771-2781; Circulation  2019;140:1639-1646]

“Taking into account the limited statistical power of any subanalysis of a large, controlled trial, our results highlight the ambiguous effects of anticoagulation in patients with device-detected AF, including in patients with multiple comorbidities and with long device-detected AF episodes,” he said, highlighting the need for new methods to identify which patients might benefit from anticoagulation.

In a news release, senior study author Prof Paulus Kirchhof of UKE stated: “The findings are consistent with the main trial, [that] the stroke rate in patients with device-detected AF is low, even with multiple comorbidities. Anticoagulation had only a minor effect on stroke and systemic embolism.

“Our results, together with other data and considering the limitations of all subgroup analyses, can help to adapt the safe and effective use of oral anticoagulants in patients with device-detected AF and multiple stroke risk factors in clinical practice, and in future guidelines,” Kirchoff added.