Patients with advanced heart failure with preserved ejection fraction (HFpEF) will be randomly assigned in open-label multicenter study to receive triple combination therapy with \[angiotensin receptor/neprilysin inhibitor \[ARNI\] + sodium-glucose cotransporter 2 inhibitor \[SGLTi\] + mineralocorticoid receptor antagonist \[MRA\]) or with individualized medical therapy \[SGLTi + renin-angiotensin system inhibitor \[RASi\] \[angiotensin receptor blocker \[ARB\] or angiotensin-converting enzyme inhibitor \[ACE-I\]), and will be treated for 52 weeks
HFpEF has a significant morbidity and mortality, and the therapeutic options for HFpEF are limited. According to the results of clinical HFpEF trials, SGLTis and MRA can improve prognosis (EMPEROR-preserved, DELIVER, FINEARTS-HF trials); and ARNI can reduce the risk of hospitalization due to exacerbation of heart failure (PARAGON-HF trial). There is also clinical and experimental evidence of anti-inflammatory and antifibrotic effects in SGLTi, MRA and ARNI. However, there are currently no randomized clinical trials evaluating the efficacy of the combination therapy with all these drugs in HFpEF. The investigators suppose that triple combination therapy with \[ARNI + SGLTi + AMR\] in HFpEF will have a pronounced, rapid and safe positive clinical and haemodynamic effect primarily through its effect on fibrosis and inflammation in patients with HFpEF.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Empagliflozin 10mg tablet, Valsartan+Sacubitril 100-200-400 mg tablet, Finerenone 20-40 mg tablet
Empagliflozin 10mg tablet, previously taken RAAS inhibitor
Change in myocardial extracellular volume (MRI)
Difference in myocardial extracellular volume assessed by MRI data between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in 6-minute walking distance (6MWD)
Difference in distance walked during 6-minute walking test (6MWT) between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)
Difference in NT-proBNP plasma levels between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in average E/e' ratio and tricuspid regurgitation velocity
Difference in E/e' ratio and tricuspid regurgitation velocity assessed by echocardiography both at rest and at peak exercise during diastolic stress test (DST) between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in left atrial volume index (LAVi)
Difference in LAVi assessed by echocardiography between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in left ventricular mass index (LVMi)
Difference in LVMi assessed by MRI between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score
Difference in Minnesota Living with Heart Failure Questionnaire (MLHFQ, potential scoring range between 0 and 105; higher scores mean a worse outcome) score between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Difference in Kansas City Cardiomyopathy Questionnaire (KCCQ; a range of possible subscale scores is from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three subscale scores) score between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in biomarkers of inflammation and fibrosis
Difference in plasma levels of inflammatory and fibrosis biomarkers (hsCRP, GDF-15, PICP, galectin-3, MCP-1) between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in cardiac hemodynamic reserves - LV contractile
Difference in cardiac hemodynamic reserves (LV contractile) during DST between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in cardiac hemodynamic reserves - LV diastolic
Difference in cardiac hemodynamic reserves (LV diastolic) during DST between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in cardiac hemodynamic reserves - LA reservoir
Difference in cardiac hemodynamic reserves (LA reservoir) during DST between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in cardiac hemodynamic reserves - cardiac chronotropic
Difference in cardiac hemodynamic reserves (cardiac chronotropic) during DST between 52 weeks after baseline and at baseline
Time frame: 52 weeks
Change in cardiac hemodynamic reserves - RV contractile
Difference in cardiac hemodynamic reserves (RV contractile) during DST between 52 weeks after baseline and at baseline
Time frame: 52 weeks
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