The APULEIO Study: an Italian, multicenter, prospective, observational experience evaluating the psychologic effects of Apixaban in the elderly

Background: Apixaban (APX) is a NOAC prescribed in patients with non-valvular atrial fibrillation (NVAF) and deep vein thrombosis (DVT) and pulmonary embolism (PE). The APULEIO study was specifically designed to describe, in an Italian elderly population with NVAF, DVT or PE, the effects of APX on health-related quality of life (HRQL), depressive symptoms and treatment satisfaction. Real-world data on these topics, essential to improve compliance and adherence to therapy, are effectively lacking. Methods: APULEIO was a multicentre, prospective, observational, two-cohort study including patients eligible to anticoagulant therapy for either NVAF or DVT/PE (Italian participating centres – N 1⁄4 43; enrolment period: April 22nd, 2016 - January 31st, 2017). Patients, starting APX treatment, were followed-up at 3 and 6 months. The Anti-Clot Treatment Scale (ACTS) was used to assess patient satisfaction; the 12- Item Short Form Health Survey (SF-12), the Beck Depression Inventory-II (BDI-II) and the FIND questionnaire were used to evaluate HRQL, depressive symptoms and frailty status, respectively. Continuous variables are expressed as median with interquartile (IQR) range. Results: Out of 441 enrolled patients, 371 had the complete dataset and could be analysed (NVAF—N1⁄4285, 77%; DVT/PE—N1⁄486, 23%). NVAF subjects were older (76 vs. 71years; p<0.0001) with a higher prevalence of hypertension (83.5 vs. 52.3%, p < 0.0001), cerebrovascular disease (16.1 vs. 7.0%, p 1⁄4 0.0330) and congestive heart failure (13.7 vs. 4.7%, p 1⁄4 0.0210); accordingly, their Charlson Comorbidity Index was higher. No differences were observed in gender, body mass index, resting heart rate and the prevalence of disabled and frail individuals (39.4 and 30.9% respectively). Median time from diagnosis was higher in NVAF patients (1.9 vs. 0.9months; p1⁄40.0002). The most used daily dosage of APX was 10mg in both cohorts (IQR(10; 10)). At the 6-month evaluation, SF-12 showed a significant improvement in the whole population, with an increase of both the Physical (difference: þ2.0, IQR(-3.1; 8.8), p<0.0001; Baseline: 40.4 IQR(33.3; 47.7)) and the Mental Health Composite Score (difference: þ2.1, IQR(-4.6; 9.0), p 1⁄4 0.0002; Baseline: 47.1, IQR (38.9; 54.4)). Also depressive symptoms, as evaluated with the BDI-II had a significant improvement (difference: -1.0, IQR(-6.0; 2.0), p < 0.0001; Baseline: 7.0, IQR (3.0; 13.0)). Importantly, at 6 months, the psychologic burden of therapy, as measured with the ACTS score, did not change at all (difference: 0.0, IQR(-1.0; 2.0), p1⁄40.3351; Baseline: 57, IQR (53; 59)). All these results were identical also separately analysing NVAF and DVT/PE subjects. HRQL and the presence of comorbidities influenced the degree of patients’ satisfaction to therapy. Haemoglobin concentration (Baseline: 13.4g/dL) and glomerular filtration rate (Baseline: 68mL/min) did not vary during the follow-up (respectively, p 1⁄4 0.4365 and p 1⁄4 0.7104 vs. Baseline). The incidence of any adverse events was 9.2%. Conclusions: The APULEIO Study shows that APX therapy in an elderly population with both NVAF and DVT/PE is well tolerated. In the first 6-month of treatment, HRQL and depressive symptoms significantly improve, while drug-related psychologic burden is unchanged. These findings are particularly important because of the high prevalence of a disabled and a frail condition in our population.