Portal de investigação
Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Packer, M
- Butler, J
- Zeller, C
- Pocock, SJ
- Brueckmann, M
- Filippatos, G
- Usman, MS
- Zannad, F
- Anker, SD
Unidades de investigação
Abstract
BACKGROUND: It is not known whether the benefits of sodium-glucose cotransporter 2 inhibitors in heart failure persist after years of therapy. METHODS: In the EMPEROR-Reduced (Empagliflozin Outcome Trials in Chronic Heart Failure With Reduced Ejection Fraction) and EMPEROR-Preserved (Empagliflozin Outcome Trials in Chronic Heart Failure With Preserved Ejection Fraction) trials, patients with heart failure were randomly assigned (double-blind) to placebo or empagliflozin 10 mg/day for a median of 16 and 26 months, respectively. At the end of the trials, 6799 patients (placebo 3381, empagliflozin 3418) were prospectively withdrawn from treatment in a blinded manner, and, of these, 3981 patients (placebo 2020, empagliflozin 1961) underwent prespecified in-person assessments after approximate to 30 days off treatment. RESULTS: From 90 days from the start of closeout to the end of double-blind treatment, the annualized risk of cardiovascular death or hospitalization for heart failure was lower in empagliflozin-treated patients than in placebo-treated patients (10.7 [95% CI, 9.0-12.6] versus 13.5 [95% CI, 11.5-15.6] events per 100 patient-years, respectively; hazard ratio 0.76 [95% CI, 0.60-0.96]). When the study drugs were withdrawn for approximate to 30 days, the annualized risk of cardiovascular death or hospitalization for heart failure increased in patients withdrawn from empagliflozin but not in those withdrawn from placebo (17.0 [95% CI, 12.6-22.1] versus 14.1 [95% CI, 10.1-18.8] events per 100 patient-years for empagliflozin and placebo, respectively). The hazard ratio for the change in risk in the patients withdrawn from empagliflozin was 1.75 (95% CI, 1.20-2.54), P=0.0034, whereas the change in the risk in patients withdrawn from placebo was not significant (hazard ratio 1.12 [95% CI, 0.76-1.66]); time period-by-treatment interaction, P=0.068. After withdrawal, the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score declined by 1.6 +/- 0.4 in patients withdrawn from empagliflozin versus placebo (P<0.0001). Furthermore, withdrawal of empagliflozin was accompanied by increases in fasting glucose, body weight, systolic blood pressure, estimated glomerular filtration rate, N-terminal pro-hormone B-type natriuretic peptide, uric acid, and serum bicarbonate and decreases in hemoglobin and hematocrit (all P<0.01). These physiological and laboratory changes were the inverse of the effects of the drug seen at the start of the trials during the initiation of treatment (approximate to 1-3 years earlier) in the same cohort of patients. CONCLUSIONS: These observations demonstrate a persistent effect of empagliflozin in patients with heart failure even after years of treatment, which dissipated rapidly after withdrawal of the drug.
Dados da publicação
- ISSN/ISSNe:
- 0009-7322, 1524-4539
- Tipo:
- Article
- Páginas:
- 1011-1022
- Link para outro recurso:
- www.scopus.com
Circulation Lippincott Williams and Wilkins Ltd.
Citações Recebidas na Web of Science: 1
Citações Recebidas na Scopus: 18
Documentos
- Não há documentos
Filiações
Keywords
- empagliflozin; heart failure; sodium-glucose transporter 2 inhibitors; substance withdrawal syndrome
Campos de estudo
Financiamento
Proyectos asociados
Dapagliflozin, Spironolactone or Both for HFpEF (SOGALDI-PEF) - NCT05676684
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (SOGALDI-PEF) . AstraZeneca . 2022
Initiation of ARNi and SGLT2i in Patients With HFrEF: Randomized Open-label Trial (INITIATE-HFrEF) -NCT05989503
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (INITIATE-HFrEF) . Novartis . 2023
Citar a publicação
Packer M,Butler J,Zeller C,Pocock SJ,Brueckmann M,Ferreira JP,Filippatos G,Usman MS,Zannad F,Anker SD. Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure. Circulation. 2023. 148. (13):p. 1011-1022. IF:37,800. (1).
