BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

• MeSH
• antikoagulancia * škodlivé účinky   terapeutické užití   MeSH
• cévní mozková příhoda etiologie   prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• embolie * farmakoterapie   etiologie   MeSH
• fibrilace síní komplikace   diagnóza   MeSH
• implantované elektrody MeSH
• inhibitory faktoru Xa * škodlivé účinky   terapeutické užití   MeSH
• krvácení chemicky indukované   MeSH
• lidé MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční arytmie * komplikace   diagnóza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• cévní mozková příhoda * etiologie   prevence a kontrola   diagnóza   MeSH
• fibrilace síní * komplikace   farmakoterapie   diagnóza   MeSH
• lidé MeSH
• pyridiny * MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční síně MeSH
• thiazoly * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Epizody rychlé frekvence síní (atrial high‐rate episodes, AHRE) jsou síňové arytmie detekované implantovanými srdečními zařízeními. Dosud nebylo známo, zda nás výskyt AHRE u pacientů bez fibrilace síní opravňuje k zahájení an­ti­ko­agu­lač­ní léčby. Událostmi řízená dvojitě zaslepená, randomizovaná klinická studie NOAH‐AFNET 6 zahrnula pacienty ve věku 65 let nebo starší, kteří měli AHRE trvající alespoň šest minut a alespoň jeden další rizikový faktor pro vznik cévní mozkové příhody (CMP). Pacienti byli randomizováni v poměru 1 : 1 k podávání edoxabanu nebo placeba. Primární cílový ukazatel účinnosti byl složen z kardiovaskulárního úmrtí, CMP nebo systémové embolie a hodnocen v analýze doby do události. Bezpečnostní cílový ukazatel zahrnoval úmrtí z jakékoliv příčiny nebo velké krvácení. U pacientů s AHRE detekovanými implantabilními zařízeními antikoagulace edoxabanem ve srovnání s placebem významně nesnížila incidenci kardiovaskulárního úmrtí, CMP nebo systémové embolie, ale vedla k vyššímu výskytu úmrtí nebo velkého krvácení. Výskyt CMP byl v obou skupinách nízký.

AHRE (atrial high‐rate episodes) may be detected by implantable cardiac devices. So far, it is not clear whether AHRE unaccompanied by atrial fibrillation mandates the initiation of anticoagulation therapy. In the event‐driven, double blind, randomized clinical trial NOAH‐AFNET 6, patients aged 65 or older with a history of AHRE lasting at least 6 minutes and at least one more risk factor for stroke were investigated. They were randomized 1:1 to edoxaban or placebo. The composite primary endpoint consisted of cardiovascular death, stroke and systemic embolization – time to event was analyzed. All‐cause death and major bleeding represented the safety endpoint. In patients with AHRE detected by implantable cardiac devices, anticoagulation with edoxaban did not ensure significant decrease in the incidence of cardiovascular death, stroke and systemic embolization while it was associated with higher incidence of all‐cause death and major bleeding (compared to placebo). The stroke rate was low in both groups.

• Klíčová slova
• edoxaban, studie NOAH-AFNET 6,
• MeSH
• antikoagulancia * klasifikace   terapeutické užití   MeSH
• cévní mozková příhoda etiologie   mortalita   MeSH
• dvojitá slepá metoda MeSH
• embolie etiologie   mortalita   MeSH
• fibrilace síní * diagnóza   farmakoterapie   MeSH
• kardiovaskulární nemoci klasifikace   mortalita   MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční arytmie diagnóza   farmakoterapie   klasifikace   MeSH
• srdeční frekvence účinky léků   MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• randomizované kontrolované studie MeSH