In patients with HF with preserved ejection fraction and an exercise-induced increase in a metric of left ventricular filling pressure, spironolactone was associated with a boost in exercise capacity, according to results of the STRUCTURE trial.
Although previous studies have not shown a benefit associated with spironolactone in patients with HFpEF, the researchers investigated whether the drug improved exercise capacity in patients with HFpEF who had their ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e’), a marker for elevated LV filling pressure, increased by exercise.
They randomly assigned 150 patients (mean age, 67 years; 84% women) with HFpEF, exertional dyspnea and exertional E/e’ > 13 but without ischemic heart disease from a single center to spironolactone 25 mg per day or placebo for 6 months; 131 patients completed 6 months of therapy.
The primary outcomes were improvements in peak oxygen uptake (VO2) and E/e’ ratio under exertion. Secondary outcomes included improved exercise BP response and global LV longitudinal strain.
Improved exercise capacity
Compared with the placebo group, the spironolactone group had improved exercise capacity, with an increment in peak VO2 of 2.9 mL/min/kg (95% CI, 1.9-3.9) vs. 0.3 mL/min/kg for the placebo group (95% CI, –0.5 to 1.1), Wojciech Kosmala, MD, PhD, from the cardiology department at Wroclaw Medical University in Poland, and colleagues wrote.
Anaerobic threshold was 2 mL/min/kg (95% CI, 0.9-3.2) in the spironolactone group vs. –0.9 mL/min/kg in the placebo group (95% CI, –3.4 to 1.6), whereas O2 uptake efficiency was 0.19 (95% CI, 0.06-0.31) in the spironolactone group vs. –0.07 in the placebo group (95% CI, –0.17 to 0.04) in the placebo group.
Exercise-induced increase in E/e’ was reduced in the spironolactone group compared with the placebo group (–3; 95% CI, –3.9 to –2; vs. 0.5; 95% CI, –0.6 to 1.6).
Kosmala and colleagues observed a significant interaction between spironolactone and change in E/e’ on VO2 (P for interaction = .039).
“The addition of spironolactone to existing therapy for 6 months in patients with HFpEF and abnormal diastolic response to exertion led to increased exercise capacity independent of changes in BP, and ... improvement in LV diastolic filling at exercise ... might be a contributor to this beneficial effect,” the researchers wrote.
In a related editorial, Brett C. Lampert, DO, and William T. Abraham, MD, both from the division of cardiovascular medicine, The Ohio State University Wexner Medical Center, Columbus, wrote, “The use of exercise capacity as a primary outcome is an important concept that should carry more significance in future HFpEF trials, as exercise limitation is often severe in patients with HFpEF.
William T. Abraham
“Spironolactone may possess the unique benefits in HFpEF of decreasing fibrosis, lowering [BP] and improving volume status,” but it needs more study in larger, multicenter trials, they wrote. – by Erik Swain
The researchers, Abraham and Lampert report no relevant financial disclosures.