IMPORTANCE Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. OBJECTIVE To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient's lifetime.DESIGN, SETTING, AND PARTICIPANTS Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months.INTERVENTIONS Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. MAIN OUTCOMES AND MEASURESThe primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient's lifetime for the primary outcome and the secondary outcome of death from any cause.RESULTS A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. CONCLUSIONS AND RELEVANCEThese findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03036124
Objective: To determine whether the benefits of dapagliflozin in patients with heart failure and reduced ejection fraction (HFrEF) and type 2 diabetes in DAPA-HF varied by background glucose-lowering therapy (GLT). Research design and methods: We examined the effect of study treatment by the use or not of GLT, and by GLT classes and combinations. The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Results: In the 2139 type 2 diabetes patients, the effect of dapagliflozin on the primary outcome was consistent by GLT use/no use (hazard ratio 0.72 [95%CI 0.58-0.88] versus 0.86 [0.60-1.23]; P-interaction=0.39) and across GLT classes. Conclusions: In DAPA-HF, dapagliflozin improved outcomes irrespective of use/no use of GLT or by GLT type used in patients with type 2 diabetes and HFrEF.
Background: Although indicators of surgical and medical treatment have been applied to patients with typical dissection (AD) of the descending thoracic aorta, the natural history of descending aortic intramural hematoma (AIH) is not yet clearly known.Objective: The goal of this study was to test the hypothesis that the absence of flow communication through the intimal tear in AIH involving the descending aorta has a different clinical course compared with AD.Methods: We prospectively evaluated clinical and echocardiographic data between AD (76 patients) and AIH (27 patients) of the descending thoracic aorta.Results: Patients had no differences In age, gender, or clinical presentation. The development of pleural effussion or periaortic hematoma was more frequent in patients with AIH than it was in patients with AD. AIH and AD had same predictors of complications at follow-up: aortic diameter (>5 cm) at diagnosis and persistent back pain. Although medical treatment was selected in the same proportion between groups, surgical treatment was more frequently selected in AD (39% vs. 22%, p < 0.01). AD patients who received surgical treatment had higher mortality than those with AIH (36% vs. 17%, p < 0.01). There was no difference in mortality between patients who received medical treatment (15% in AD vs 14% in AIH, p = 0.7). In follow-up imaging studies of 23 patients with AIH,6 patients (25%) showed complete resolution and 6 patients (25%) increased the descending aortic diameter. Typical AD developed in 3 patients (13%). A three-year survival rate did not show significant difference (82 ± 6% in AIH vs 75 ± 7% in AD, p = 0.37).Conclusion: AIH of the descending thoracic aorta have relatively frequent complications at follow-up including dissection and aneurysm formation. Medical treatment with very close imaging follow-up and timed elective surgery in cases with complications allow better management for patients with AIH of the descending thoracic aorta.
El objetivo primario del estudio es la evaluación mediante el uso de Ecocardiografía Doppler Tisular de distintos parámetros de función diastólica en pacientes con Diabetes Mellitus Juvenil Insulinodependiente (DMID) de corta duración, y la correspondiente comparación con los resultados de una población similar en pacientes normales sanos. Asimismo se plantea como objetivo secundario en este grupo de pacientes la evaluación de la función diastólica con Ecocardiografía Doppler convencional, mediante el análisis del flujo transmitral y su correlación con los hallazgos del Doppler Tisular. De igual forma, es objetivo del presente estudio valorar las diferencias miocárdicas regionales de las velocidades de Doppler Tisular en pacientes diabéticos juveniles y su correlación con los hallazgos en pacientes normales sanos.
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