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
Signed and data informed consent;
Symptoms and signs of HF;
LV ejection fraction > 50%;
NT-proBNP > 300 pg/mL (for patients with atrial fibrillation NT-proBNP > 900 pg/mL)
Evidence of myocardial ischemia during stress echocardiography;
Significant lesions of main coronary arteries;
Atrial fibrillation with resting HR > 110 beats/min;
Continuous (>90 days) treatment with ARNI, SGLTi and/or AMR within 12 months prior to screening. The last administration of these drugs must be at least 30 days prior to randomization. Treatment with these drugs should not be interrupted for the purpose of inclusion in the study.
Parallel
[ARNI + SGLTi + AMR]
DrugEmpagliflozin 10mg tablet, Valsartan+Sacubitril 100-200-400 mg tablet, Finerenone 20-40 mg tablet
[SGLTi + previously taken RAAS blocker]
DrugEmpagliflozin 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
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
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
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
Change in left ventricular mass index (LVMi)
Difference in LVMi assessed by MRI between 52 weeks after baseline and at baseline
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
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
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
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National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Lead sponsor
Lomonosov Moscow State University Medical Center
Collaborator
