Advance in the pharmacological and comorbidities management of heart failure with preserved ejection fraction: evidence from clinical trials.

The prevalence of heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of the total heart failure population, and with the aging of the population and the increasing prevalence of hypertension, obesity, and type 2 diabetes (T2DM), the incidence of HFpEF continues to rise and has become the most common subtype of heart failure. Compared with heart failure with reduced ejection fraction, HFpEF has a more complex pathophysiology and is more often associated with hypertension, T2DM, obesity, atrial fibrillation, renal insufficiency, pulmonary hypertension, obstructive sleep apnea, and other comorbidities. HFpEF has generally been considered a syndrome with high phenotypic heterogeneity, and no effective treatments have been shown to reduce mortality to date. Diuretics and comorbidity management are traditional treatments for HFpEF; however, they are mostly empirical due to a lack of clinical evidence in the setting of HFpEF. With the EMPEROR-Preserved and DELIVER results, sodium-glucose cotransporter 2 inhibitors become the first evidence-based therapies to reduce rehospitalization for heart failure. Subgroup analyses of the PARAGON-HF, TOPCAT, and CHARM-Preserved trials suggest that angiotensin receptor-neprilysin inhibitors, spironolactone, and angiotensin II receptor blockers may be beneficial in patients at the lower end of the ejection fraction spectrum. Other potential pharmacotherapies represented by non-steroidal mineralocorticoid receptor antagonists finerenone and antifibrotic agent pirfenidone also hold promise for the treatment of HFpEF. This article intends to review the clinical evidence on current pharmacotherapies of HFpEF, as well as the comorbidities management of atrial fibrillation, hypertension, T2DM, obesity, pulmonary hypertension, renal insufficiency, obstructive sleep apnea, and iron deficiency, to optimize the clinical management of HFpEF.