What does the PRAISE-HF trial say about GLP-1 (Glucagon-like peptide-1) receptor agonists in patients with Heart Failure with reduced Ejection Fraction (HFrEF)?

The FIGHT Trial and GLP-1 Receptor Agonists in HFrEF

There is No "PRAISE-HFREF" Trial

The trial you're asking about does not exist—you may be thinking of the FIGHT trial (Functional Impact of GLP-1 for Heart Failure Treatment), which is the landmark study examining liraglutide in HFrEF patients. 1

What the FIGHT Trial Actually Showed

The FIGHT trial demonstrated that liraglutide provides no benefit in HFrEF and showed a concerning trend toward increased heart failure readmissions and adverse cardiac events. 1

Trial Design and Population

• The FIGHT trial randomized 300 patients with chronic HFrEF and recent heart failure hospitalization to liraglutide 1.8 mg daily or placebo for 6 months 1
• Patients were enrolled regardless of diabetes status, making this applicable to all HFrEF patients 1

Primary Findings: No Benefit, Possible Harm

• Liraglutide had no effect on post-hospitalization clinical stability 1
• Heart failure readmission rates were numerically higher with liraglutide: 41% versus 34% (HR 1.30,95% CI 0.89-1.88) 1, 2
• The risk was even more pronounced in the diabetic subgroup: HR 1.54 (95% CI 0.97-2.46) for the composite of death and HF hospitalization 1, 2

Corroborating Evidence: The LIVE Trial

The Danish LIVE trial (241 patients with stable HFrEF) reinforced these concerning findings 1:

• Liraglutide showed no improvement in left ventricular ejection fraction, quality of life, or functional class at 24 weeks 1
• Serious adverse cardiac events occurred significantly more often with liraglutide than placebo: 10.0% versus 3.0% (P=0.04) 1, 2
• These events included sustained ventricular tachycardia, atrial fibrillation requiring intervention, and aggravation of ischemic heart disease 1, 2

Mechanistic Concerns Explaining the Negative Results

GLP-1 receptor agonists cause physiologic changes that are potentially detrimental in HFrEF:

• Heart rate increases by 3-10 beats per minute due to direct sinus node effects, which can worsen outcomes in decompensated heart failure 1, 2
• Systolic blood pressure decreases by 2-3 mm Hg, which may contribute to variable results in HF populations 1, 2

Current Guideline Recommendations Based on These Trials

The American Heart Association and Heart Failure Society of America explicitly state that GLP-1 receptor agonists should be used with caution in patients with established HFrEF and recent decompensation. 1, 2

Clinical Algorithm for GLP-1 RA Use in HFrEF:

In patients WITHOUT established HFrEF:

• GLP-1 RAs are safe and beneficial for reducing major adverse cardiovascular events and mortality in diabetic patients at cardiovascular risk 2
• They show no effect on preventing HF hospitalizations but are not harmful 1

In patients WITH stable HFrEF:

• Use GLP-1 RAs with extreme caution 1, 2
• If diabetes management requires a GLP-1 RA, monitor closely for: heart rate increases, signs of HF decompensation, atrial fibrillation, and ventricular tachycardia 2

In patients WITH recent HF decompensation:

• Avoid GLP-1 RAs entirely—they provide no benefit and trend toward worse outcomes 1, 2

Prioritize SGLT2 inhibitors over GLP-1 RAs when diabetes management is needed in HFrEF patients, as SGLT2 inhibitors demonstrate clear mortality and HF hospitalization benefits 2

Common Pitfall to Avoid

Do not confuse the cardiovascular benefits of GLP-1 RAs in primary prevention trials (LEADER, SUSTAIN-6, HARMONY) with their effects in established HFrEF 1. These cardiovascular outcome trials showed MACE reduction but no effect on HF hospitalization, and they enrolled patients at cardiovascular risk, not patients with established HFrEF 1. The HFrEF-specific trials (FIGHT and LIVE) tell a different and concerning story 1.