This study aimed to collect data on "triple therapy" for heart failure (HF) with angiotensin-converting enzyme inhibitors (or receptor blockers), β-blockers, and mineralocorticoid receptor ...antagonists in all eight regions of Japan and clarify the reason for the selection of this therapeutic approach.
We used data from April 2017 to March 2018 from the Medical Data Vision database (380 facilities) to analyze factors impacting triple therapy for HF. Among patients who were hospitalized for HF during the study period, 51,933 patients met the inclusion criteria and underwent further analyses. A reference value of 20.45% from Kanto was used to compare the eight Japanese regions. From the patient cohort, 10,006 (19.27%) patients receiving triple therapy were identified. The highest and lowest rates of triple therapy were in Chugoku (21.90%) and Shikoku (14.27%), respectively, suggesting regional differences in the use of triple therapy at discharge for patients with HF (P < 0.001). Regression analysis revealed a decrease in the administration of triple therapy for patients with chronic kidney disease (odds ratio OR, 0.45; 95% confidence interval CI, 0.43-0.48; P < 0.001), those aged 75 years and older (OR, 0.46, 95% CI: 0.44-0.49; P < 0.001), those from Shikoku (OR, 0.69; 95% CI, 0.60-0.80; P < 0.001), those with chronic obstructive pulmonary disease (OR, 0.75; 95% CI, 0.68-0.84; P < 0.001), those with anemia (OR, 0.78; 95% CI, 0.62-0.98; P = 0.034), and those from Tohoku (OR, 0.83; 95% CI, 0.75-0.92; P < 0.001).
Future efforts to rectify the regional variance in drug therapy conforming to the guidelines for the treatment of acute and chronic HF will help to extend the healthy lifespans of patients with HF. Further clarification is required to determine instances where triple therapy should be avoided based on patient factors, and appropriate countermeasures should be identified.
Background:Although diuretic resistance leading to residual congestion is a known predictor of a poorer heart failure (HF) prognosis, better therapeutic strategies for effective and safe decongestion ...have not been established.Methods and Results:In this study, 81 HF patients with fluid retention (despite taking ≥40 mg/day furosemide (FUR)), with an estimated glomerular filtration rate <45 mL/min/1.73 m2, were randomized into 2 groups and administered either ≤15 mg/day additive tolvaptan (TLV) or ≤40 mg/day increased FUR for 7 days. Changes in urine volume between baseline and mean urine volume during treatment were significantly higher in the TLV than FUR group (P=0.0003). Although there was no significant decrease in body weight or improved signs and symptoms of congestion between the 2 groups, the increase in serum creatinine on Day 7 from baseline was significantly smaller in the TLV than FUR group (P=0.038). Multiple logistic regression analysis revealed that additive TLV (odds ratio 0.157, 95% confidence interval 0.043–0.605, P=0.001) was an independent clinical factor for improved renal function during treatment compared with increased FUR.Conclusions:In HF patients with residual congestion and renal dysfunction refractory to standard therapy, additive TLV increased urine volume without further renal impairment compared with patients who received an increased dose of FUR.
The present meta-analysis aimed to evaluate effects of tolvaptan on fluid retention in patients with heart failure who were non-responsive to conventional treatment and to assess differences between ...effects of low (≤ 15 mg/day) and high (> 15 mg/day) tolvaptan doses.Randomized controlled trials comparing add-on tolvaptan therapy and placebo or therapy with other diuretics in patients with heart failure were identified through a database search. The primary outcomes were changes in body weight and urine volume, and the secondary outcomes were changes in serum sodium and creatinine levels.In total, 14 reports were analyzed using a random effects model. Add-on tolvaptan was associated with increased urine volume mean difference (MD), 1.44 L; 95% confidence interval (CI), 0.96 to 1.92, decreased body weight (MD, −0.99 kg; 95% CI, −1.24 to −0.74), and increased serum sodium levels (MD, 3.66 mEq/L; 95% CI, 3.43 to 3.88) within 2 days. Serum creatinine levels on day 7 were not different between the groups (MD, −0.03 mg/dL; 95% CI, −0.09 to 0.03). The high-dose group showed greater changes in urine volume, body weight, and serum sodium levels than the low-dose group. Serum creatinine levels slightly increased in the high-dose group (MD, 0.06; 95% CI, 0.04 to 0.08) and slightly decreased in the low-dose group (MD, −0.10; 95% CI, −0.19 to −0.01).Our findings suggest that add-on tolvaptan therapy for heart failure improves fluid retention in the early therapy phase. However, this drug should be properly used to avoid the worsening of renal function, which may occur at high doses.
Background:Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and ...reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.Methods and Results:Patients with NYHA functional class II–IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40–1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760).Conclusions:The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.
Background:In Japan, tolvaptan is indicated for patients with heart failure and volume overload who have inadequate response to other diuretics. In contrast to the USA and Europe, tolvaptan can be ...used in Japan in patients with normal sodium levels.Methods and Results:In this multicenter, non-interventional, post-marketing surveillance study, prospective data from 3,349 patients treated with tolvaptan over a 5-year period were analyzed to identify benefits and risks. By Day 2 of treatment, 76.9% of evaluable patients had an increase in baseline 24-h urine volume (tolvaptan responders). Mean change in body weight was similar between 7.5 mg and 15 mg dosage groups (−3.6±3.9 kg and −3.7±4.0 kg, respectively). Improvement or disappearance rates for congestive symptoms from baseline to Day 14 ranged from 77.7% for lower limb edema to 51.1% for 3rd sound. Adverse drug reactions were reported in 18.1% of patients, most frequently thirst (8.4%). No case of central pontine myelinolysis was reported. All-cause mortality was significantly lower in patients with improved sodium concentration and increased 24-h urine volume.Conclusions:The effectiveness and safety of tolvaptan in real-world clinical settings was confirmed in this large-scale analysis. The 7.5-mg dose was equally as effective as the 15-mg dose and had a better safety profile. Improvements in all-cause mortality were suggested in tolvaptan responders.
A 59-year-old man with aortic stenosis (AS) showed cardiopulmonary arrest requiring extracorporeal circulation. Although coronary angiography did not show coronary artery stenosis, he had an elevated ...creatine kinase-myocardial band value of 1,298 U/L. Echocardiography revealed severe AS and global hypokinesia of the thickened myocardium. Contrast-enhanced computed tomography (CT) detected a circumferential subendocardial perfusion defect of the left ventricular myocardium. Eventually, the patient died from brain anoxia. Autopsy revealed circumferential subendocardial infarction of the left ventricular myocardium. This is the first case of circumferential subendocardial defect on CT corresponding to circumferential subendocardial infarction on autopsy in severe AS without coronary stenosis
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