Spironolactone yielded neutral results for cardiovascular mortality and heart failure hospitalizations in HFmrEF/HFpEF patients, with only ~50% of participants remaining on therapy by 21 months.
In older, multi-morbid patients with HFpEF and HFmrEF, the effectiveness of neurohormonal therapies depends heavily on sustained use and long-term tolerability, not just intrinsic pharmacologic efficacy.
Taken together, the findings from SPIRIT-HF challenge a simplistic interpretation of neutral trial results from an under-powered study, and instead appear to highlight the critical role of treatment durability in determining clinical outcomes in heart failure with preserved ejection fraction and heart failure with mildly reduced ejection fraction, where patients are older, multi-morbid, and physiologically vulnerable, the balance between efficacy and tolerability is particularly fragile. Importantly, treatment discontinuation should not be viewed merely as an adverse event, but as a clinically meaningful signal reflecting both patient vulnerability and potential loss of therapeutic benefit. These observations suggest that the effectiveness of neurohormonal therapies may depend as much on their sustained use as on their intrinsic pharmacologic efficacy. Accordingly, future therapeutic strategies should prioritize not only the initiation of disease-modifying treatments but also their long-term tolerability, adherence, and continuity.
“There might be a beneficial effect of spironolactone in these patients if they are able to be on drug treatment.”
Copeland et al. (Tue,) conducted a editorial in Heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF) (n=730). Spironolactone vs. Placebo was evaluated on Recurrent heart failure hospitalizations over 24 months and cardiovascular mortality. Spironolactone yielded neutral results for cardiovascular mortality and heart failure hospitalizations in HFmrEF/HFpEF patients, with only ~50% of participants remaining on therapy by 21 months.