The inability of trials to demonstrate reduced mortality in HFmrEF/HFpEF likely reflects lower baseline mortality rates and fewer modifiable cardiovascular deaths compared to HFrEF.
The inability to show mortality benefit in HFmrEF/HFpEF trials is likely due to statistical power limitations driven by lower baseline event rates of modifiable cardiovascular deaths, rather than a lack of treatment efficacy.
No randomized controlled trial has yet demonstrated a statistically significant reduction in mortality in patients with heart failure and mildly reduced ejection (HFmrEF) or heart failure and preserved ejection fraction (HFpEF), in contrast to the benefits observed in heart failure with reduced ejection fraction (HFrEF). However, this probably reflects the statistical power of trials to date to show an effect on mortality rather than mechanistic differences between HFmEF/HFpEF and HFrEF or differences in treatment efficacy. Compared to patients with HFrEF, those with HFmrEF/HFpEF have lower mortality rates and a smaller proportion of potentially modifiable cardiovascular deaths (as opposed to unmodifiable noncardiovascular deaths). In addition, some causes of cardiovascular deaths may not be reduced by treatments for HF. Therefore, the low rate of potentially modifiable deaths in patients with HFmrEF/HFpEF, compared with HFrEF, has made it challenging to demonstrate a reduction in death (or cardiovascular death) in trials to date.
“No randomized controlled trial has yet demonstrated a statistically significant reduction in mortality in [these] patients, in contrast to the benefits observed in [HF] with reduced ejection fraction (HFrEF).”
Kondo et al. (Sun,) conducted a review in Heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF). Heart failure treatments was evaluated on Mortality. The inability of trials to demonstrate reduced mortality in HFmrEF/HFpEF likely reflects lower baseline mortality rates and fewer modifiable cardiovascular deaths compared to HFrEF.