AimsWe used the US Department of Defense Military Health System database to compare the safety and effectiveness of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) initiating dabigatran vs. rivaroxaban or apixaban.Methods and resultsTwo cohorts of adults with NVAF, newly initiated on standard-dose DOAC, were identified based on clinical approval dates: July 2011–June 2016 for dabigatran (150 mg b.i.d.) or rivaroxaban (20 mg QD) and January 2013–June 2016 for dabigatran (150 mg b.i.d.) or apixaban (5 mg b.i.d.). Propensity score matching (1:1) identified two well-balanced cohorts (dabigatran vs. rivaroxaban n = 12 763 per treatment group; dabigatran vs. apixaban n = 4802 per treatment group). In both cohorts, baseline characteristics and follow-up duration were similar between treatment groups. Patients newly initiating dabigatran had significantly lower risk of major bleeding vs. rivaroxaban [2.08% vs. 2.53%; hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.70–0.97; P = 0.018], while stroke risk was similar (0.60% vs. 0.78%; HR 0.77, 95% CI 0.57–1.04; P = 0.084). The dabigatran vs. apixaban cohort analysis found no differences in risk of major bleeding (1.60% vs. 1.21%; HR 1.37, 95% CI 0.97–1.94; P = 0.070) or stroke (0.44% vs. 0.35%; HR 1.26, 95% CI 0.66–2.39; P = 0.489).ConclusionAmong NVAF patients newly initiated on standard-dose DOAC therapy in this study, dabigatran was associated with significantly lower major bleeding risk vs. rivaroxaban, and no significant difference in stroke risk. For dabigatran vs. apixaban, the reduced sample size limited the ability to draw definitive conclusions.

AimIn the EMPEROR‐Preserved trial, empagliflozin improved clinical outcomes of patients with heart failure (HF) with preserved ejection fraction. In this pre‐specified analysis, we aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function.Methods and resultsPatients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (CKD defined by an estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or urine albumin to creatinine ratio >300 mg/g). The primary and key secondary outcomes were (i) a composite of cardiovascular death or first HF hospitalization (primary outcome); (ii) total number of HF hospitalization, (iii) eGFR slope; and a pre‐specified exploratory composite kidney outcome including a sustained ≥40% decline in eGFR, chronic dialysis or renal transplant. The median follow‐up was 26.2 months. A total of 5988 patients were randomized to empagliflozin or placebo, of whom 3198 (53.5%) had CKD. Irrespective of CKD status, empagliflozin reduced the primary outcome (with CKD: hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69–0.94; without CKD: HR 0.75, 95% CI 0.60–0.95; interaction p = 0.67) and total (first and recurrent) hospitalizations for HF (with CKD: HR 0.68, 95% CI 0.54–0.86; without CKD: HR 0.89, 95% CI 0.66–1.21; interaction p = 0.17). Empagliflozin slowed the slope of eGFR decline by 1.43 (1.01–1.85) ml/min/1.73 m2/year in patients with CKD and 1.31 (0.88–1.74) ml/min/1.73 m2/year in patients without CKD (interaction p = 0.70). Empagliflozin did not reduce the pre‐specified kidney outcome in patients with or without CKD (with CKD: HR 0.97, 95% CI 0.71–1.34; without CKD: HR 0.92, 95% CI 0.58–1.48; interaction p = 0.86) but slowed progression to macroalbuminuria and reduced the risk of acute kidney injury. The effect of empagliflozin on the primary composite outcome and the key secondary outcomes was consistent across five baseline eGFR categories (all interaction p >0.05). Empagliflozin was well tolerated independent of CKD status.ConclusionsIn EMPEROR‐Preserved, empagliflozin had a beneficial effect on the key efficacy outcomes in patients with and without CKD. Overall, the benefit and safety of empagliflozin was consistent across a wide range of kidney function spectrum, down to a baseline eGFR of 20 ml/min/1.73 m2.

ClinicalTrials.gov NCT01896297.

Purpose: To assess costs and healthcare resource utilization (HCRU) associated with the use of idarucizumab for the reversal of dabigatran and andexanet alfa for the reversal of direct oral Factor Xa inhibitors. Methods: This retrospective study utilizing Premier Healthcare Database (PHD) included patients aged ≥18 years on direct oral anticoagulants (DOACs) who experienced life-threatening bleeds, discharged from the hospital during 5/1/2018–6/30/2019, and received idarucizumab or andexanet alfa. Inverse of treatment probability weighting (IPTW) method was used to balance patient and clinical characteristics between treatment cohorts. Results: Idarucizumab patients were older than andexanet alfa patients (median age 81 vs 77 years; p < 0.001), and less likely to experience intracranial hemorrhage (ICH) (37.1%vs 73.8%; p  =  0.001). After IPTW adjustment, idarucizumab patients incurred lower mean total hospital costs ($30,413  ±  $33,028 vs $44,477  ±  $30,036; p < 0.001),and mean intensive care unit (ICU) cost ($25,114  ±  $30,433 vs $43,484  ±  $29,335; p < 0.001). Conclusions: Anticoagulant reversal therapy with idarucizumab was associated with significantly lower adjusted mean total hospital and ICU costs compared with andexanet alfa. However, a higher prevalence of ICH bleeds was noted in the andexanet alfa group. Trial Registration: Not applicable.

Background:The objective of the study was to describe the healthcare resource utilization (HCRU) and associated costs with hospitalized patients receiving specific versus non-specific oral anticoagulation reversal therapy for life-threatening bleeds and emergency surgeries or urgent procedures.Methods: This retrospective observational study using the Premier Healthcare Database included adult patients aged ≥ 18 years treated with idarucizumab (IDA) or 3-or 4-factor prothrombin complex concentrates (PCC) to reverse the effects of dabigatran or warfarin, respectively, between October 2015 and February 2018.Results: Median ages for IDA (n = 1,232) and PCC (n = 4,939) patients were 78 and 74 years (P < 0.001), respectively. IDA patients had lower bleeding and stroke risk assessment scores (HAS-BLED; P < 0.001 and CHA 2 DS 2 -VASc; P = 0.014) and lower prevalence of comorbidities compared with PCC patients. Median hospital length of stay was 6 and 7 days for patients who received IDA or PCC (P < 0.001), respectively. The percentage of patients with an intensive care unit (ICU) admission was lower for IDA patients compared with PCC patients (61.3% vs. 68.7%; P < 0.001). Median total costs per hospitalization were $19,357 for IDA patients and $26,920 for PCC patients (P < 0.001). Median costs per hospitalization for IDA and PCC treatment were $3,277 and $4,424, respectively. When HCRU and costs were examined by cause of reversal and type of bleed, similar trends in hospitalized costs emerged for IDA compared with PCC treatment.Conclusions: This analysis revealed lower HCRU and total hospital costs in patients administered IDA compared with PCC for reversal of oral anticoagulation, though differences in population characteristics and bleeding events were observed that may have contributed to these findings.