Triple Combination Therapy (ARNI, SGLT2i, MRA) in Advanced HFpEF

Launched by NATIONAL MEDICAL RESEARCH CENTER FOR CARDIOLOGY, MINISTRY OF HEALTH OF RUSSIAN FEDERATION · Oct 21, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with advanced heart failure with preserved ejection fraction (HFpEF), a condition where the heart pumps normally but has trouble filling with blood. The study will compare a combination of three medications—an angiotensin receptor/neprilysin inhibitor (ARNI), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), and a mineralocorticoid receptor antagonist (MRA)—against a standard treatment plan that includes a different SGLT2i and other heart medications. Participants will be involved for 52 weeks, during which their health will be closely monitored to see how well this combination therapy works.

To be eligible for this study, participants must be adults showing symptoms of heart failure, have specific heart function measurements, and meet certain health criteria. For example, they should have a left ventricular ejection fraction greater than 50% and elevated levels of a blood marker called NT-proBNP. However, those with certain heart conditions, recent surgeries, or significant health issues like uncontrolled high blood pressure or certain types of kidney problems cannot participate. This trial is not yet recruiting, so those interested will need to wait until it opens for enrollment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Signed and data informed consent;
• • 2. Symptoms and signs of HF;
• • 3. LV ejection fraction \> 50%;
• • 4. NT-proBNP \> 300 pg/mL (for patients with atrial fibrillation NT-proBNP \> 900 pg/mL)
• • 5. LV diastolic dysfunction II-III grade OR
• LV diastolic dysfunction I grade and at least 2 out of 4:
• • Е/е' \> 14
• • LAVi \> 34 ml/m2 (for those with persistent atrial fibrillation \> 40 ml/m2)
• • PASP \> 35 mm Hg or TR velocity \> 2.8 m/sec
• • LV mass index \> 95 g/m2 for women / \> 115 g/m2 for men or LV interventricular septum or posterior wall thickness ≥ 1.1 sm OR
• Chronic atrial fibrillation and at least 3 out of 4:
• • Е/е' \> 11
• • E-wave velocity \> 100 sm/s
• • TR velocity \> 2.8 sm/s
• • DT ≤ 160 ms
• Exclusion Criteria:
• • 1. Evidence of myocardial ischemia during stress echocardiography;
• • 2. Significant lesions of main coronary arteries;
• • 3. Atrial fibrillation with resting HR \> 110 beats/min;
• • 4. 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.
• • 5. Coronary bypass surgery, stroke or TIA within the last 3 months of screening;
• • 6. Myocardial infarction or myocardial revascularization within the last 3 months of screening;
• • 7. Systolic blood pressure \< 90 mmHg or ≥ 180 mmHg at screening or randomization;
• • 8. Genetic forms of HFpEF (HCM, amyloidosis, Fabry disease, glycogen storage diseases etc.);
• • 9. Peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, viral myocarditis, isolated right-sided HF without left-sided structural disease, constrictive pericarditis, significant pericardial effusion;
• • 10. Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;
• • 11. Significant lung disease (severe lung disease requiring home oxygen or chronic oral steroid therapy);
• • 12. Primary pulmonary artery hypertension;
• • 13. Significant left sided structural valve disease;
• • 14. Anemia (Hb \< 100 g/L);
• • 15. Obesity (body mass index \> 50 kg/m2);
• • 16. Impaired renal function, defined as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (CKD-EPI);
• • 17. Impaired liver function (serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 × upper limit of normal);
• • 18. Addison's disease;
• • 19. Known hypersensitivity to medications used the in the study;
• • 20. Non-cardiac conditions that complicate/exclude participation in the study;
• • 21. Diseases associated with isolated LV insufficiency (idiopathic pulmonary hypertension, chronic thromboembolic pulmonary hypertension, etc.);
• • 22. Serum/plasma potassium \>5.0 mmol/L at screening or randomization or a history of hyperkalemia or acute renal failure during AMR treatment for \>7 consecutive days leading to discontinuation of AMR treatment.
• 23. For patients with diabetes mellitus:
• • Type 1 diabetes mellitus;
• • Presence of more than 4 episodes of moderate hypoglycemia within the past month or at least one episode of severe hypoglycemia within the past year;
• • Glycated hemoglobin level \> 9% or \<6%