Клиническое значение результатов исследования DAPA HF (Dapagliflozin and prevention of adverse-outcomes in heart failure) для пациентов и врачей. Консенсус совета Экспертов

2021 ◽  
Vol 1 (223) ◽  
pp. 2-14
Author(s):  
Gulmira Alipova ◽  
◽  
Anna Bazarova ◽  
Nazira Bazarova ◽  
Rimma Bazarbekova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Persistent Symptoms

The article presents the results of the DAPA-HF study - evaluating the efficacy of dapagliflozin, used at a dose of 10 mg once a day, in addition to the standard treatment for patients with chronic heart failure with reduced left ventricular ejection fraction, compared to placebo. An analysis of current clinical recommendations related to this issue was carried out, the results of recent clinical studies and metaanalyses conducted were highlighted. Based on the results of the study, the need is postulated to optimize drug therapy of this category to patients with persistent symptoms of heart failure, despite standard therapy, with the addition of dapagliflozin to reduce the risk of cardiovascular death and hospitalizations for heart failure, improve the course of the disease. Keywords: chronic heart failure, dapagliflozin, low ejection fraction, effects of type 2 sodium-glucose co transporter inhibitors, diabetes mellitus.

Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide: Insights From the DAPA-HF Trial

2021 ◽  
Author(s):  
Jawad H. Butt ◽  
Carly Adamson ◽  
Kieran F. Docherty ◽  
Rudolf A. de Boer ◽  
Mark C. Petrie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Natriuretic Peptide ◽  
Geometric Mean ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Meaningful Improvement ◽  
Ventricular Ejection Fraction

Background: Effective therapies for HFrEF usually reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP. Methods: We evaluated both these questions in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and a NT-proBNP level ≥600 pg/mL (≥600 ng/L; ≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter) were eligible. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Results: Of the 4744 randomized patients, 4742 had an available baseline NT-proBNP measurement (median, 1437 pg/mL [interquartile range, 857–2650 pg/mL]). Compared with placebo, treatment with dapagliflozin significantly reduced NT-proBNP from baseline to 8 months (absolute least-squares mean reduction, −303 pg/mL [95% CI, −457 to −150 pg/mL]; geometric mean ratio, 0.92 [95% CI, 0.88–0.96]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of baseline NT-proBNP quartile; the hazard ratio for dapagliflozin versus placebo, from lowest to highest quartile was 0.43 (95% CI, 0.27–0.67), 0.77 (0.56–1.04), 0.78 (0.60–1.01), and 0.78 (0.64–0.95); P for interaction=0.09. Consistent benefits were observed for all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement (≥5 points) in Kansas City Cardiomyopathy Questionnaire total symptom score ( P for interaction=0.99) and decreased the proportion with a deterioration ≥5 points ( P for interaction=0.87) across baseline NT-proBNP quartiles. Conclusions: In patients with HFrEF, dapagliflozin reduced NT-proBNP by 300 pg/mL after 8 months of treatment compared with placebo. In addition, dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, across the spectrum of baseline NT-proBNP levels included in DAPA-HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

Mode of Death in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF Trial

2021 ◽  
Author(s):  
Akshay S. Desai ◽  
Muthiah Vaduganathan ◽  
John G. Cleland ◽  
Brian L. Claggett ◽  
Ebrahim Barkoudah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Mode Of Death

Background: Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction. Methods: PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms. Results: Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P <0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30). Conclusions: Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920711.

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