#Topcat mobile trial
12, 13 Since activation of the mineralocorticoid receptor by aldosterone is known to promote hypertension, endothelial dysfunction, left ventricular hypertrophy, and progressive vascular, renal, and myocardial fibrosis, all of which may contribute to the development of HF-PEF, the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial sought to test the value of spironolactone as a treatment for HF-PEF. The mineralocorticoid receptor antagonists spironolactone and eplerenone reduce morbidity and mortality in patients with HF-REF. Accordingly, treatment guidelines for this population underscore that no specific therapies are available to reduce morbidity and mortality in the HF-PEF population. Moreover, therapeutic trials of digoxin (Ancillary Digitalis Investigation Group trial 8) and β-blockers (SENIORS 9) that enrolled HF-PEF patients have failed to demonstrate conclusive benefits in this subgroup. Even though neurohormonal activation typical of the heart failure syndrome is apparent in HF-PEF, 4 three large-scale, prospective randomized trials have shown no statistically significant impact of angiotensin-converting enzyme inhibition 5 or angiotensin receptor blockade (CHARM-Preserved, 6 I-PRESERVE 7) on clinical outcomes in HF-PEF. The dramatic success of renin–angiotensin system inhibition as a strategy for reducing morbidity and mortality amongst patients with HF-REF has fuelled several efforts to replicate these benefits in heart failure and preserved ejection fraction (HF-PEF). 1, 2 Although patients with heart failure and preserved ejection fraction (HF-PEF) experience rates of hospitalization, functional decline, and mortality similar to patients with heart failure and reduced ejection fraction (HF-REF), 3 limited understanding of key pathophysiologic mechanisms has challenged the development of targeted pharmacologic therapy for this population. Heart failure with preserved ejection fraction, Spironolactone, Clinical management BackgroundĪpproximately one-half of patients with heart failure have normal or near normal left ventricular ejection fraction and the proportion is growing.
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