The following is the summary of “Meta-Analysis on Drug and Device Therapy of New York Heart Association Functional Class IV Heart Failure With Reduced Ejection Fraction” published in the 1 February 2023 issue of Cardiovascular Disease by Batchelor, et al.

Significant morbidity and mortality are associated with heart failure with reduced ejection fraction (HFrEF), especially in individuals with New York Heart Association (NYHA) functional class IV symptoms. The pharmacologic therapy of HFrEF has come a long way in the last few decades because of extensive research. However, clinicians have little data to use when making pharmacological treatment decisions for patients with severe heart failure who have NYHA Class IV symptoms. In addition, this cohort has been under-represented in practically all clinical trials.

This systematic review and meta-analysis comprised randomized controlled trials of adult patients with NYHA IV symptoms of HFrEF who were randomly assigned to receive the medical therapy recommended by current guidelines. All-cause mortality, cardiac death, and hospitalizations due to heart failure were considered important outcomes. There were a total of 39 randomized studies included. Angiotensin-converting enzyme inhibitors were the subject of 6 investigations; 2 meta-analyses showed that they lowered the risk of death from any cause (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.59 to 0.97, P=0.03). The risk of death from any cause was lower for those taking beta blockers in a meta-analysis of 6 of the eleven studies that looked at them (risk ratio 0.74, 95% confidence interval 0.60 to 0.92, P=0.008). The risk of death from any cause was lower in the NYHA IV subgroup of participants who used the mineralocorticoid antagonist spironolactone. 

New York Heart Association, functional class IV patients can benefit from cardiac resynchronization therapy with or without an implanted cardiac defibrillator, according to a meta-analysis of 6 trials that looked at device therapy. The relevance of angiotensin receptor blockers in the NYHA IV population is uncertain, despite trial evidence for angiotensin-converting enzyme inhibitors, -blockers, and mineralocorticoid antagonist therapy. Patients with HFrEF and NYHA Class IV symptoms have not been shown to benefit from adding ivabradine, angiotensin receptor neprilysin inhibitors, or sodium-glucose transport protein 2 inhibitors to routine heart failure medication.