Beta-blockers, RASBs reduce mortality in HF patients with midrange EF

Guideline-directed medical therapies (GDMTs) like beta-blockers and renin-angiotensin system blockers (RASBs)—but not aldosterone antagonists (AAs)—are associated with improved outcomes in heart failure patients hospitalized with a midrange ejection fraction, researchers reported in the current edition of the Journal of the American Heart Association.

New European Society of Cardiology guidelines define heart failure with midrange ejection fraction (HFmrEF) as a left ventricular EF of between 40 and 49 percent, first author Ki Hong Choi, MD, and co-authors said in the journal, and beta-blockers and RASBs are recommended as class IA indications for all symptomatic patients. AAs are recommended for patients who don’t respond to those treatments, but GDMTs haven’t actually been proven to reduce mortality or morbidity in HFmrEF patients.

“It is unclear if the prognosis of HFmrEF is similar to that of HFpEF, HFrEF or a new ‘gray area’ group,” Choi, of Sungkyunkwan University School of Medicine in Seoul, South Korea, and colleagues wrote.

To answer that question, the team performed a patient-level pooled analysis of 1,144 HFmrEF patients enrolled in the Korean Heart Failure and Korean Acute Heart Failure registries. The study population was matched and randomized to treatment with either beta-blockers, RASBs or AAs.

After sensitivity analyses, the researchers found patients taking beta-blockers saw lower rates of all-cause mortality than those not taking the drugs (30.7 percent versus 38.2 percent, respectively), and patients taking renin-angiotensin system blockers also saw improved numbers over those not taking RASBs (31.9 percent versus 38.1 percent).

However, there was no significant difference in all-cause mortality between HFmrEF patients taking AAs and those not taking them during the follow-up period, which was an average of 1.7 years in the Korean Heart Failure registry and an average of 2.1 years in the Korean Acute Heart Failure registry.

“Observational studies consistently show a lack of benefit with AA, but randomized controlled trials consistently show a benefit for patients with HFrEF,” the authors said. “Perhaps this result might be a failure of method rather than a lack of benefit from AA.

“Because AAs were recommended to be prescribed to those who remained symptomatic taking the medication of RASB and beta-blocker, those with AAs might be more severe patients with worse prognosis, although we performed propensity-matching analysis.”

Still, the study did succeed in proving the efficacy of at least some GDMTs in heart failure patients with a midrange ejection fraction, Choi and co-authors wrote.

“Our results suggest that the use of beta-blocker and RASB in HFmrEF is associated with reduced risk of mortality, similar to heart failure with reduced ejection fraction,” they said. “Future randomized controlled trials are warranted to clarify whether guideline-directed medical therapy would improve prognosis of patients with HFmrEF.”