Patients with obesity more often receive optimal GDMT in HFrEF

Use of and association between heart failure pharmacological treatments and outcomes in obese versus non-obese patients with heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry

Literature - Cappelletto C, Stolfo D, Orsini N, et al. - Eur J Heart Fail. 2023 Feb 13. doi: 10.1002/ejhf.2795.

Introduction and methods


Approximately 40% of patients with HFrEF is obese (BMI ≥ 30 kg/m²) [1]. Nevertheless, this patient population is underrepresented in RCTs in HFrEF. Registry-based studies on large HF cohorts may provide insight how guideline-directed medical therapies (GDMT) affect patients with HF with and without obesity.

Aim of the study

This study investigated the use and dosing of GDMT and associated outcomes in patients with HFrEF with and without obesity.



Patients from the Swedish HF Registry (SwedeHF) with HFrEF, <6 months after HF diagnosis, and with available BMI data were included in this study. 16,116 patients (73% male) with registrations from 10 May 2000 and 31 December 2019 were included. 12,171 patients (76%) did not have obesity and 3,945 patients (24%) had obesity. Patients with obesity were younger compared to patients without obesity (mean 71 vs 77 years old). GDMT for HFrEF included, at the time, RASi/ARNI, beta-blockers, MRAs and a combination of RASi/ARNI, beta-blockers and MRAs (referred to as triple therapy). SGLT2i were not considered as they were introduced as GDMT for HFrEF after data collection. The median follow-up period was 2.21 years (IQR 0-17).


The primary outcome was 5-year all-cause mortality. Secondary outcomes were 5-year CV-mortality, and 5-year first HF hospitalization.

Main results

Use of GDMT

  • Obesity was independently associated with the use of RASi/ARNI (OR: 1.21; 95%CI: 1.05-1.39; P=0.008), beta-blocker (OR: 1.28; 95%CI: 1.09-1.50; P=0.002), MRA (OR: 1.29; 95%CI: 1.19-1.40; P=0.001), and triple therapy (OR: 1.30; 95%CI: 1.19-1.42; P<0.001).
  • Obesity was also independently associated with achievement of ≥100% TD for all drug treatments (RASi/ARNI (OR: 1.21; 95%CI: 1.11-1.32; P<0.001), beta-blocker (OR: 1.41; 95%CI: 1.30-1.54; P<0.001), MRA (OR: 1.52; 95%CI: 1.27-1.81; P<0.001), and triple therapy (OR: 2.25; 95%CI: 1.66-3.05; P<0.001).


  • The incidence of all-cause mortality was 47% in patients with obesity vs 62% in patients without obesity. The incidence of CV mortality was 30% in patients with obesity and 42% in patients without obesity. The incidence of HF hospitalization was similar in both patients groups (both 44%).
  • Use of RASi/ARNI was associated with lower risk of all-cause mortality (adjusted HR: 0.70; 95%CI: 0.61-0.80, for patients with obesity vs adjusted HR: 0.78; 95%CI: 0.73-0.84; P for interaction=0.115, for patients without obesity) and CV mortality (adjusted HR: 0.65; 95%CI: 0.55-0.77, for patients with obesity vs adjusted HR: 0.77; 95%CI: 0.72-0.85, P for interaction=0.060), regardless of obesity. HF hospitalization was lower in patients treated with RASi/ARNI in the overall study population, but a significant lower risk of HF hospitalization was detected only in patients with obesity (adjusted HR: 0.78; 95%CI: 0.66-0.92) and not in patients without obesity (adjusted HR: 0.94; 95%CI: 0.86-1.03; P for interaction=0.034).
  • Competing risk analysis showed that the lower risk associated with RASi/ARNI for CV mortality (competing event: non-CV mortality) was greater in patients with obesity (adjusted sub HR: 0.70; 95%CI: 0.60-0.82) compared to patients without obesity (adjusted sub HR: 0.84; 95%CI: 0.78-0.91; P for interaction=0.033). Conversely, competing risk analysis showed that there was no interaction between obesity and RASi/ARNI for HF hospitalization (competing event: all-cause mortality).
  • Use of beta-blockers was associated with a lower risk of all-cause mortality (adjusted HR: 0.87; 95%CI: 0.81-0.95; P<0.001) and CV mortality (adjusted HR: 0.84; 95%CI: 0.76-0.93; P<0.001), but not of HF hospitalization (adjusted HR: 0.93; 95%CI: 0.84-1.02; P=0.127). There was not difference in these outcomes between patients with and without obesity. Moreover, competing risk analysis showed that there was no interaction between beta-blockers and CV mortality or HF hospitalization with obesity.
  • There was no association of RASi/ARNI or beta blocker with risk of all-cause mortality, CV mortality and HF hospitalization when BMI was evaluated as a continuous variable.


Patients with HFrEF and with obesity more often received GDMT and with higher dosages, even after adjusting for factors related to tolerance. This suggests that perceived tolerance issues, but not necessary the actual tolerance issue, limits GDMT in a portion of patients with HFrEF.

RASi/ARNI and beta blockers were associated with lower mortality regardless of obesity. Competing risk analysis showed that this association of RASi/ARNI with lower risk of CV mortality was greater in patients with obesity. In addition, RASi/ARNI was associated with lower risk of HF hospitalization in patients with obesity compared to patients without obesity.

The authors highlight that “our results do not completely exclude a different effectiveness of HF treatments in obese versus non-obese patients, but represent a call for further and more focused research adopting e.g., more precise parameters to assess obesity (measurements of adipose tissue distribution, waist-to-hip ratio, etc.) and more adequate study design, e.g., stratified randomization according to obesity in RCTs.”.


1. Carbone S, Lavie CJ, Arena R. Obesity and heart failure: focus on the obesity paradox. Mayo Clin Proc. 2017;92(2):266-279. doi: 10.1016/j.mayocp.2016.11.001.

Find this article online at Eur J Heart Fail.

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