Trial Data Suggest Beta Blockers Not Best Choice in Heart Failure With Preserved Ejection Fraction

Beta blockers, long a mainstay in caring for patients with heart failure (HF), may actually contribute to hospitalizations for those with one type of the condition, a new study finds.

A second look at data from the TOPCAT trial, which was designed to study spironolactone (Aldactone), found that hospitalization was 74% more likely among patients with HF with preserved ejection fraction (HFpEF) who were taking a beta blocker than those who were not. This effect did not hold up among patients with reduced ejection fraction (HFrEF).

The authors caution that their findings must be examined more directly, because the trial was randomized to study a different drug. Adjustments made for variables cannot account for all of them, including how long patients took beta blockers. Also, the results contrast with earlier randomized trials of beta blockers, which the author say did not show higher hospitalizations among patients with HFpEF.

The results are sure to generate interest as HFpEF lacks treatment options, but that could change as results are expected in outcomes trials that are studying sodium glucose co-transporter 2 (SGLT2) inhibitors in HF, both preserved and reduced ejection fraction (EF).

The current analysis looked at 1761 patients who took part in the TOPCAT trial from Augsut 20016 to January 2012. Of the group, 1394 (79.2%) reported using beta blockers, and 1567 had had an EF of 50% or greater, or preserved. Among this group, use of beta blockers was associated with higher risk of hospitalization, for a hazard ratio [HR] of 1.74 (95% CI, 1.28-2.37; P <.001).

Among the smaller group of patients with reduced EF (between 45% and 49%), the HR was 0.68 (95% CI, 0.28-1.63; P = .39). Researchers found a significant interaction between use of beta blockers and EF status for the number of HF hospitalizations (P = .03). However, there was no similar link with cardiovascular mortality.

Some recent evidence may offer insight into the mechanism behind the findings. The LIFE trial explained a possible risk of HF due to increased central blood pressure and found “prolonged diastolic filling increases ventricular volumes and pressures, increasing the ventricular load.” The authors say the combination increases stress on the heart wall.

The bottom line, the authors say, is that more research is needed. “Prospective studies of the role of beta blockers play in heart failure among patients with a preserved ejection fraction appears to be warranted to clarify the effectiveness of these drugs for patients with an ejection fraction of 50% or greater,” they wrote.

Reference

Silverman DN, Plante TB, Infeld M, et al. Association of beta blocker use with heart failure hospitalizations and cardiovascular disease mortality among patients with heart failure with a preserved ejection fraction: a secondary analysis of the TOPCAT trial. JAMA Netw Open. 2019;2(12):e1916598. doi: 10.1001/jamanetworkopen.2019.16598.