ABSTRACT
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.).
Subject(s)
Anticoagulants , Arrhythmias, Cardiac , Embolism , Factor Xa Inhibitors , Aged , Female , Humans , Male , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Embolism/drug therapy , Embolism/etiology , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Hemorrhage/chemically induced , Stroke/etiology , Stroke/prevention & control , Electrodes, Implanted , Double-Blind Method , Arrhythmias, Cardiac/complications , Arrhythmias, Cardiac/diagnosis , Risk FactorsABSTRACT
OBJECTIVES: Hypertrophic cardiomyopathy is a complex and relatively common genetic cardiac disease and has been the subject of intensive scrutiny and investigation for over 40 years. The aim of this non-randomized cohort study was to compare subjective and objective outcomes in hypertrophic cardiomyopathy patients undergoing drug therapy, surgical myotomy-myectomy, dual-chamber pacing and alcohol septal ablation. METHODS: We examined 194 patients: 103 with non-obstructive hypertrophic cardiomyopathy and 91 with obstructive hypertrophic cardiomyopathy. All the patients with a non-obstructive form were on drug therapy. Ninety-one consecutive patients with drug-refractory obstructive hypertrophic cardiomyopathy were treated invasively. Dual-chamber pacemaker implantation was performed for 49 patients with previous positive temporary pacing test (Group 1). In 28 patients with massive left ventricle hypertrophy and obliteration of its cavities, extensive myotomy-myectomy was performed (Group 2). In 14 patients with midventricular obstruction and appropriate coronary anatomy, alcohol septal ablation was performed (Group 3). RESULTS: The peak left ventricle outflow tract gradient was 84.1 ± 15.2 mmHg in Group 1, 113.3 ± 14.9 mmHg in Group 2 and 97.5 ± 8.9 mmHg in Group 3. Dual-chamber pacing in Group 1 with optimal atrio-ventricular delay (85-180 ms for atrium pacing and 45-120 ms for atrial sensing) leads to dramatic decreases in left ventricle outflow tract gradient to 17.6 ± 11.8 mmHg and degree of mitral regurgitation. After extensive myectomy in Group 2, we observed a reduction of left ventricle outflow tract gradient to 17.3 ± 10.2 mmHg. Septal alcohol ablation in Group 3 leads to a left ventricle outflow tract gradient decrease from 97.5 ± 8.9 to 25.3 ± 5.8 mmHg. CONCLUSIONS: Surgical myectomy, dual-chamber pacing and alcohol septal ablation are equally effective in reducing obstruction in case of correct indications. Dual-chamber pacing is indicated in functional reversible states characterized by excitation delay. Alcohol septal ablation is preferable in cases with midventricular obstruction and appropriate coronary anatomy. Surgical methods are indicated in anatomical irreversible changes and remain the gold standard for obstructive hypertrophic cardiomyopathy treatment.
