Screening‐guided spironolactone treatment of subclinical left ventricular dysfunction for heart failure prevention in at‐risk patients

Abstract

Aims Subclinical left ventricular dysfunction (LVD) is a prelude to symptomatic heart failure (HF). We hypothesised that screening‐guided treatment with spironolactone would prevent incident HF in at‐risk patients. Methods and results We randomised asymptomatic, community‐dwelling subjects aged ≥65 years old, with at least one non‐ischaemic HF risk factor (hypertension, type 2 diabetes mellitus or obesity) to echocardiography‐guided therapy or usual care. Spironolactone therapy was triggered by the detection of subclinical LVD (global longitudinal strain [GLS] ≤16%) or diastolic abnormalities (at least one of E/e′ >15, E/e′ >10 with left atrial enlargement [LAE] or impaired relaxation [E/A < 0.8, IR], LAE with IR), or borderline GLS (17%) with IR or borderline GLS with LAE. The primary outcome was incident HF at 24 months. Secondary outcomes were change in 6‐min walk test (6MWT) and change in left ventricular function. LVD was identified in 161 (46%) of 349 participants (age 70 [68–73] years, 201 [58%] women). The trial was stopped because of a 55% rate of spironolactone discontinuation, due primarily to decline in renal function. Incident HF developed in 11 (3.5%) of 310 participants completing follow‐up, with no difference between usual care and intervention (4 [2.5%] vs. 7 [4.7%], p = 0.29), decline in 6MWT distance (p = 0.28), persistent or new LVD (p = 0.58), nor change in GLS with intervention (p = 0.15). A per‐protocol analysis of 131 patients with baseline LVD and a follow‐up echocardiogram, showed resolution of LVD with spironolactone therapy (59% vs. 33%, p = 0.01). Conclusion The study was underpowered to determine whether screening‐guided spironolactone therapy reduced incident HF because spironolactone was frequently discontinued due to renal function criteria. However, LVD resolved in more patients treated with spironolactone than in untreated patients. Future trials should use less conservative renal criteria for spironolactone discontinuation.

April 2022 at a glance: focus on prevention, acute heart failure and heart failure with preserved ejection fraction

“…The trial was prematurely terminated, and thus unpowered, because of a 55% withdrawal of spironolactone due to decline in renal function. However, resolution of left ventricular dysfunction occurred more frequently with spironolactone versus placebo (59% vs. 33%, p = 0.01) 2 …”

“…However, resolution of left ventricular dysfunction occurred more frequently with spironolactone versus placebo (59% vs. 33%, p = 0.01). 2 Type 2 diabetes is a well-known cardiovascular (CV) risk factor. [3][4][5] In the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, patients with cardiac autonomic neuropathy, compared to those without, had a 2.7-fold higher risk to develop HF, over a median follow-up of 4.9 years.…”

Is it time to shift our focus from treatment to prevention of heart failure with a mineralocorticoid receptor antagonist?

“…The results of Vic‐ELF 2 and the prior studies should prompt investigators to explore the role of both the steroidal and non‐steroidal MRAs to prevent HF. Once HF develops, it increases cardiovascular mortality and recurrent hospitalizations or urgent visits for HF, decreases quality of life and increases healthcare costs.…”

“…In this issue of the Journal, Potter et al 2 . shift our focus from the treatment of HF to its prevention.…”

“…However, their use remains suboptimal, especially in patients with chronic kidney disease (CKD) but also in patients with normal renal function due to the fear of HK and/or a decrease in renal function 10 . The results of Vic‐ELF, 2 MIRAD, 4,5 HOMAGE 6 along with the monitoring parameters for serum K + and renal function shown to be effective in HOMAGE 6 suggest that in patients with normal renal function the steroidal MRAs can be tolerated. Should HK occur, the administration of a new K + ‐lowering agent, such as patiromer, should allow persistence of their use as suggested by PEARL‐HF and AMBER 11,12 .…”