Spironolactone effect on the blood pressure of patients at risk of developing heart failure: an analysis from the HOMAGE trial

Abstract

Background Uncontrolled blood pressure (BP) increases the risk of developing heart failure (HF). The effect of spironolactone on BP of patients at risk of developing HF is yet to be determined. Aims To evaluate the effect of spironolactone on the BP of patients at risk for HF and whether renin can predict spironolactone`s effect. Methods HOMAGE (Heart OMics in Aging) was a prospective multicenter randomized open-label blinded Endpoint (PROBE) trial including 527 patients at risk for developing HF randomly assigned to either spironolactone (25-50mg/day) or usual care alone for a maximum of 9 months. Sitting BP was assessed at baseline, month 1 and 9 (or last visit). Analysis of covariance (ANCOVA), mixed effects models, and structural modelling equations were used. Results The median (percentile25-75) age was 73 (69-79) years, 26% were female, and >75% had history of hypertension. Overall, the baseline BP was 142/78 mmHg. Patients with higher BP were older, more likely to have diabetes and less likely to have coronary artery disease, had greater left ventricular mass (LVM), and left atrial volume (LAV). Compared with usual care, by last visit, spironolactone changed SBP by -10.3 (-13.0 to -7.5)mmHg and DBP by -3.2 (-4.8 to -1.7)mmHg (p < 0.001 for both). A higher proportion of patients on spironolactone had controlled BP < 130/80 mmHg (36 vs. 26%; p = 0.014). Lower baseline renin levels predicted a greater response to spironolactone (interactionp=0.041). Conclusion Spironolactone had a clinically important BP-lowering effect. Spironolactone should be considered for lowering blood pressure in patients who are at risk of developing HF.

Cardiac structure and function and quality of life associations in HFpEF: An analysis from TOPCAT-Americas

“…[20][21][22] In patients at risk for developing HF enrolled in the Heart Omics in Ageing (HOMAGE) trial, spironolactone reduced the size and volume of the left atria, blood pressure and circulating peptides related to collagen synthesis. [23][24][25] Increased PVR in patients with HF may be secondary to "left heart" dysfunction; however, a dedicated diagnostic workflow for increased PVR was not available in TOPCAT. 26 Notwithstanding, in patients with chronic HF the resulting pulmonary hypertension directly affects HR-QoL, exercise capacity, morbidity, and mortality.…”

SGLT2‐Inhibition reverts urinary peptide changes associated with severe COVID‐19: An in‐silico proof‐of‐principle of proteomics‐based drug repurposing

“…Investigation of the data in the urine proteome database [ 15 ] resulted in the identification and extraction of datasets from patients without COVID‐19 undergoing treatment with the aldosterone antagonist spironolactone from the HOMAGE trial [ 16 , 17 ], and the sodium‐glucose transport protein 2 (SGLT2)‐inhibitor empagliflozin [ 18 , 19 ]. As a part of the HOMAGE trial [ 16 , 17 ], the placebo group was also investigated. The details on the studies and the patient datasets included are listed in Table 1 .…”

Circulating levels of procollagen type I carboxy‐terminal propeptide reflect myocardial fibrosis

“…The latter was not evaluated in the present study, but in people at risk for heart failure participating in the Heart 'OMics' in AGEing (HOMAGE) randomized clinical trial, treatment with spironolactone (vs. usual care) for a 9-month period led to a statistically significant and clinically important drop in circulating PICP, accompanied by blood pressure reduction, improvement of cardiac structure and decrease of N-terminal pro B-type natriuretic peptide levels. 8,11,12 Whether mineralocorticoid receptor antagonists or other anti-fibrotic therapies can improve the outcomes of patients with DCM and a pro-fibrotic profile should be adequately tested in a randomized controlled trial; the background for such a trial in now robust. Conflict of interest: J.P.F.…”