paraglide hf with reduce ejection fraction

paraglide hf

1. JOURNAL OF CARDIAC FAILURE Presented by: Muhammad Aulia Kurniawan, MD Supervisor: Department of Cardiology and Vascular Medicine Faculty of Medicine Universitas Syiah Kuala/ Zainoel Abidin General Hospital Banda Aceh 2024 Rationale, Design and Baseline Characteristics of the PARAGLIDE-HF Trial: Sacubitril/Valsartan vs Valsartan in HFmrEF and HFpEF With a Worsening Heart Failure Event

2. Introduction

3. Patients with HFpEF / HFmrEF and worsening heart failure commonly have elevated natriuretic peptide levelsperiod . 01 PIONEER-HF trial showed greater NT- proBNP reduction with in-hospital Sac/Val vs enalapril initiation after decompensated HF 03 Elevated natriuretic peptide levels associated with worse outcomes 02 Post-hoc analysis found larger Sac/Val benefit vs Val in patients enrolled within 30 days after recent heart failure hospitalization 04 Introduction

4. AIMS Evaluate the efficacy of sacubitril/valsartan vs. valsartan in reducing NT- proBNP levels in HFpEF / HFmrEF patients after a recent worsening heart failure event. Assess the safety and tolerability of initiating sacubitril/valsartan in this patient population within 30 days of decompensation. Examine the effects on clinical outcomes, including in underrepresented subgroups like de novo HF, severe obesity, and Black patients.

5. , Method TREATMENT PROTOCOL Randomized 1:1 to Sac/Val (target 97/103 mg twice daily) vs Val (target 160 mg twice daily) Up to ~20 months double-blind treatment Concomitant open-label ACEi /ARB prohibited

6. INCLUSION CRITERIA Age ≥18 years Signed informed consent Currently hospitalized for worsening HFpEF or within 30 days post-discharge (required IV diuretics) Hemodynamically stable (SBP ≥100 mmHg for 6 hrs , no IV diuretic increase for 6 hrs , no IV inotropes 24 hrs , no IV vasodilators 6 hrs ) LVEF >40% within past 3 months Elevated natriuretic peptides NT- proBNP ≥500 pg /mL or BNP ≥150 pg /mL if no AF NT- proBNP ≥1000 pg /mL or BNP ≥300 pg /mL if AF No ACEi use for ≥36 hours pre-randomization

7. EXCLUSION CRITERIA Clinical event within 90 days that could have reduced LVEF, unless echo confirmed LVEF >40% Sacubitril/valsartan use within past 60 days eGFR <20 mL/min/1.73m2 Serum potassium >5.2 mEq /L Recent acute coronary syndrome, stroke, cardiac surgery/intervention within 30 days Alternative diagnoses that could account for HF symptoms Isolated right heart failure Hypersensitivity/contraindications to study drugs or angioedema history Prior heart transplant, LVAD, or on transplant list Life expectancy <6 months Pericardial constriction, hypertrophic/infiltrative cardiomyopathy, amyloidosis Uncontrolled arrhythmias Significant valvular/coronary disease likely needing intervention during study Hepatic impairment or cirrhosis with portal hypertension Pregnant/lactating women Women of childbearing potential not using effective contraception

8. STUDY ENDPOINT Primary efficacy endpoint: Time-averaged proportional change in NT- proBNP from baseline to Weeks 4 and 8 Key secondary endpoint: Win-ratio composite of cardiovascular death, HF hospitalizations, urgent HF visits, NT- proBNP changes Other secondary endpoints: Recurrent composite events (HF hospitalization, urgent visit, CV death), worsening renal function composite

9. Statistical Considerations Secondary endpoints analyzed per pre-specified plan

10. DISCUSSION

11. 52% women, 22% Black, mean age 70 years, median BMI 33 kg/m2 23% HFmrEF , 24% EF >60%, 33% de novo HF Median NT- proBNP 2009 pg /mL, median BNP 517 pg /mL Cop Baseline Characteristics

12. In the PARAGLIDE-HF trial, the median NT- proBNP level at screening was 2009 (1291-3813) pg /mL, indicating patients had significantly elevated natriuretic peptide levels likely reflecting decompensated heart failure at enrollment after a recent worsening event. The SOLOIST-WHF trial enrolled patients with diabetes and a recent worsening heart failure event, with only 20.9% having a left ventricular ejection fraction ≥50%, in contrast to PARAGLIDE-HF which exclusively studied patients with mildly reduced or preserved ejection fraction. The median baseline BMI in the PARAGLIDE-HF trial was 33 (27-40) kg/m2, higher than the other trials shown, suggesting it included a greater proportion of obese patients which is an underrepresented group in prior heart failure trials. Comparison of PARAGLIDE-HF to several recent HF trials

13. PARAGLIDE-HF Trial

14. 01 02 04 PRAGLIDE-HF complements the PARAGON-HF trial, which investigated Sac/Val in chronic heart failure with preserved ejection fraction ( HFpEF ). PARAGLIDE-HF will also complement TRANSITION and PIONEER-HF trials, which examined Sac/Val in hospitalized patients with acute decompensated heart failure with reduced ejection fraction ( HFrEF ). PARAGLIDE-HF recruited 22% Black individuals, compared to 2% in PARAGON-HF. Compared to SOLOIST-WHF and EMPULSE, PARAGLIDE-HF includes only those with ejection fraction > 40% and has greater representation of women and Black individuals. OTHER TRIALS PARTICIPANTS DIVERSITY

15. OTHER RELATED TRIALS

16. Conclusion Prior studies have shown the benefits of a medication called sacubitril/valsartan on outcomes in patients with heart failure and an ejection fraction (or “heart squeeze”) of 45% or more. More information is needed regarding the effect and safety of the medication when started in those with recent worsening of their heart failure requiring a hospitalization, ED visit or urgent clinic visit. The PARAGLIDE-HF trial studied the effect of sacubitril/ valsartan on a heart failure biomarker (“blood test”) and clinical outcomes in patients with heart failure with an ejection fraction > 40% and a recent worsening heart failure event.

17. CRITICAL APPRAISAL

18. PICO

19. Questions Yes/No Are the results of this study valid? Yes Was a defined, representative sample of patients assembled at a common? Yes Was patient follow-up sufficiently complete? Yes VALIDITY

20. IMPORTANCE Questions Yes/No Comments Are the results of this study important? Yes Yes, the conclusions state it will "inform clinical practice" for an underserved patient population lacking prior evidence How precise were the results? Yes The median (IQR) EF was 55% (50% 60%), 23% with HFmrEF (LVEF 41% 49%), 24% with EF > 60% and 33% with de novo HFpEF . Median screening NT- proBNP was 2009 (1291 3813) pg /mL, and 69% were enrolled in the hospital.

21. APPLICABILITY Questions Yes/No Can the results be applied to my patient care? Yes Were all clinically important outcomes considered? Yes Are the benefits worth the harm and costs? Yes

22. CONCLUSION Study in this journal is VALID Result of this study is IMPORTANT Result of this study is APPLICABLE in daily clinical practice. Level of Evidence: I (Randomized controlled trial design, Multi-center (100 sites), Double-blinded Clear inclusion/exclusion criteria, Reasonable sample size (467 patients),Assessed clinically relevant outcomes )

23. Thank You