Fenofibrate and Heart Failure Outcomes in Patients With Type 2 Diabetes: Analysis From ACCORD

Data de publicação: 01/07/2022

Autores da FMUP

• João Pedro Melo Marques Pinho Ferreira

  Autor

• Francisco Aguiar Vasques Novoa Faria

  Autor

• Francisca Almeida Saraiva

  Autor

• Inês Maria Falcão Sousa Pires Marques

  Autor

• João Sérgio De Lima Soares Neves

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Ferrao, D
• Sharma, A
• Rossignol, P
• Zannad, F

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

OBJECTIVE Patients with type 2 diabetes (T2D) have a high risk for developing heart failure (HF), which is associated with poor prognosis. Fenofibrate may reduce HF events through multiple mechanisms. We sought to study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the Action to Control Cardiovascular Risk in Diabetes lipid trial (ACCORD Lipid). RESEARCH DESIGN AND METHODS We used Cox regression analysis with background glucose-lowering strategy as the stratification variable. The median follow-up was 4.7 years. RESULTS A total of 5,518 patients were included. Median age was 62 years, and 31% were women. Prior HF history was present in 5% of the patients. The composite outcome of HF hospitalization or cardiovascular death occurred in 190 (6.9%) patients in the fenofibrate group vs. 228 (8.3%) in the placebo group: HR 0.82, 95% CI 0.68-1.00 (P = 0.048). The beneficial effect of fenofibrate to reduce HF hospitalizations or cardiovascular death was present among patients receiving standard glucose-lowering strategy, HR 0.64, 95% CI 0.48-0.85, and not among patients receiving intensive glucose-lowering strategy, HR 1.02, 95% CI 0.79-1.33 (P-interaction = 0.017). A similar pattern was observed for HF hospitalizations alone. The effect of fenofibrate on blood lipids was not influenced by background glucose-lowering therapy in a clinically important manner. Fenofibrate caused more transient worsening estimated glomerular filtration rate (eGFR) events but slowed long-term eGFR decline. CONCLUSIONS In patients with T2D treated with simvastatin, fenofibrate reduced the composite of HF hospitalizations or cardiovascular mortality, an effect that was seen predominantly in patients with standard background glucose-lowering therapy.

© 2022 by the American Diabetes Association.

Keywords

• Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Fenofibrate; Glucose; Heart Failure; Humans; Hypolipidemic Agents; Lipids; Male; Middle Aged; Simvastatin; 2,4 thiazolidinedione derivative; angiotensin receptor antagonist; antidiabetic agent; antithrombocytic agent; biguanide; calcium channel blocking agent; dipeptidyl carboxypeptidase inhibitor; fenofibrate; fenofibrate plus simvastatin; glucose; lipid; loop diuretic agent; mineralocorticoid antagonist; placebo; simvastatin; sulfonylurea; antilipemic agent; fenofibrate; glucose; lipid; simvastatin; adult; aged; Article; cardiovascular risk; clinical feature; confidence interval; diabetic patient; disease course; drug effect; drug mechanism; estimated glomerular filtration rate; female; follow up; hazard ratio; heart death; heart failure; hospitalization; human; lipid blood level; major clinical study; male; mediation analysis; medical history; middle aged; non insulin dependent diabetes mellitus; prognosis; proportional haz