ABSTRACT
BACKGROUND: In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population. METHODS: We performed a retrospective cohort study in ARTESiA. Using Cox regression adjusted for CHA2DS2-VASc score and treatment allocation (apixaban or aspirin), we assessed frequency of SCAF episodes and duration of the longest SCAF episode in the 6 months before randomization as predictors of stroke risk and of apixaban treatment effect. RESULTS: Among 3986 patients with complete baseline SCAF data, 703 (17.6%) had no SCAF episode ≥6 minutes in the 6 months before enrollment. Among 3283 patients (82.4%) with ≥1 episode of SCAF ≥6 minutes in the 6 months before enrollment, 2542 (77.4%) had up to 5 episodes, and 741 (22.6%) had ≥6 episodes. The longest episode lasted <1 hour in 1030 patients (31.4%), 1 to <6 hours in 1421 patients (43.3%), and >6 hours in 832 patients (25.3%). Higher baseline SCAF frequency was not associated with increased risk of stroke or systemic embolism: 1.1% for 1 to 5 episodes versus 1.2%/patient-year for ≥6 episodes (adjusted hazard ratio, 0.89 [95% CI, 0.59-1.34]). In an exploratory analysis, patients with previous SCAF but no episode ≥6 minutes in the 6 months before enrollment had a lower risk of stroke or systemic embolism than patients with at least one episode during that period (0.5% versus 1.1%/patient-year; adjusted hazard ratio, 0.48 [95% CI, 0.27-0.85]). The frequency of SCAF did not modify the reduction in stroke or systemic embolism with apixaban (Pinteraction=0.1). The duration of the longest SCAF episode in the 6 months before enrollment was not associated with the risk of stroke or systemic embolism during follow-up (<1 hour: 1.0%/patient-year [reference]; 1-6 hours: 1.2%/patient-year [adjusted hazard ratio, 1.27 (95% CI, 0.85-1.90)]; >6 hours: 1.0%/patient-year [adjusted hazard ratio, 1.02 (95% CI, 0.63-1.66)]). SCAF duration did not modify the reduction in stroke or systemic embolism with apixaban (Ptrend=0.1). CONCLUSIONS: In ARTESiA, baseline SCAF frequency and longest episode duration were not associated with risk of stroke or systemic embolism and did not modify the effect of apixaban on reduction of stroke or systemic embolism. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01938248.
ABSTRACT
INTRODUCTION: Everolimus has been prescribed both for initial and maintenance therapy after cardiac transplantation. Herein, we present our initial experience with everolimus as maintenance therapy after cardiac transplantation. METHODS: We retrospectively included all of our patients in whom therapy was changed from calcineurin inhibitors to everolimus between September 2006 and October 2007. We analyzed their baseline clinical characteristics, indications for conversion to everolimus therapy, and beneficial vs adverse effects of the maneuver. RESULTS: In 16 heart transplant recipients, therapy was changed to everolimus because of allograft vasculopathy (n = 8), renal failure (n = 4), or sirolimus toxicity (n = 4). Treatment with everolimus was initiated at a mean (SD) of 79.8 (52.7) months (range, 10-163 mo) after transplantation. The initial dose was 1.4 (0.2) mg (range, 1.0-1.5 mg), and the maintenance dose was 1 (0.31) mg (range, 0.5-1.5 mg). Follow-up was 7.28 (3.22) months (range, 0.5-13 mo). Observed side effects included hypertriglyceridemia, hypertension, and edema. Only 1 of 4 patients included because of sirolimus intolerance did not tolerate everolimus; renal dysfunction did not worsen in any of these 4 patients. No allograft vasculopathy was observed. CONCLUSIONS: Renal function seem to stabilize after conversion to everolimus therapy in patients with previous progressive dysfunction. The safety profile was proved in all patients, although conclusions cannot be established about the evolution of allograft vasculopathy.