Optimization of heart rate lowering therapy in hospitalized patients with heart failure: Insights from the Optimize Heart Failure Care Program

Background Hospitalization is an opportunity to optimize heart failure (HF) therapy. As optimal treatment for hospitalized HF patients in sinus rhythm with heart rate ≥ 70 bpm is unclear, we investigated the impact of combined beta-blocker (BB) and ivabradine versus BBs alone on short and longer term mortality and rehospitalization. Methods and results A retrospective analysis was performed on 370 hospitalized HF patients with heart rate ≥ 70 bpm (150 BB + ivabradine, 220 BB alone) in the Optimize Heart Failure Care Program in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Russia, Ukraine, and Uzbekistan, from October 2015 to April 2016. Results At 1 month, 3 months, 6 months and 12 months, there were fewer deaths, HF hospitalizations and overall hospitalizations in patients on BB + ivabradine vs BBs alone. At 12 months, all-cause mortality or HF hospitalization was significantly lower with BB + ivabradine than BBs (adjusted hazard ratio [HR] 0.45 (95% confidence interval [CI] 0.32–0.64, P < 0.0001). Significantly greater improvement was seen in quality of life (QOL) from admission to 12 months with BB + ivabradine vs BBs alone (P = 0.0001). With BB + ivabradine, significantly more patients achieved ≥ 50% target doses of BBs at 12 months than on admission (82.0% vs 66.6%, P = 0.0001), but the effect was non-significant with BBs alone. Conclusions Heart rate lowering therapy with BB + ivabradine started in hospitalized HF patients (heart rate ≥ 70 bpm) is associated with reduced overall mortality and re-hospitalization over the subsequent 12 months. A prospective randomized trial is needed to confirm the advantages of this strategy

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)