Latest guidelines on hfpef
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HFpEF guidelines 2024 2025 treatment recommendations SGLT2 inhibitors
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https://pmc.ncbi.nlm.nih.gov/articles/PMC12979370
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PMID: 41953528
I now have comprehensive information from multiple sources. Here is the full, up-to-date summary:
HFpEF: Latest Guidelines and Evidence (2025-2026)
Definition & Epidemiology
HFpEF (LVEF ≥ 50%) now accounts for >50% of all heart failure diagnoses worldwide and is rising in prevalence. It predominantly affects older adults, women, and those with obesity, hypertension, diabetes, and atrial fibrillation. It is no longer viewed as purely a diastolic disorder - it is a multifactorial systemic syndrome involving inflammation, aging, metabolic dysregulation, and comorbidities.
Pillars of Current Management
1. SGLT2 Inhibitors - Class I (Foundation of Therapy)
The single most important recent advance. Both major trials reported positive outcomes:
- EMPEROR-Preserved (empagliflozin): Reduced CV death + HF hospitalization
- DELIVER (dapagliflozin): Reduced worsening HF events + CV death
The 2023 ESC focused update upgraded SGLT2 inhibitors to a Class I, Level A recommendation for HFpEF - a historic shift from prior guidelines where no drug had Class I status. The AHA/ACC has also endorsed this.
Key points:
- Benefit seen regardless of diabetes status
- Reduced HF hospitalizations are the primary benefit
- Dapagliflozin 10 mg/day and empagliflozin 10 mg/day are both used
- Avoid in type 1 diabetes; caution with prior DKA
2. Nonsteroidal MRAs (Finerenone) - Emerging Second Pillar
FINEARTS-HF trial (2024) - landmark result:
- Finerenone (nonsteroidal MRA) significantly reduced total worsening HF events and CV death in HFmrEF/HFpEF
- Favorable hyperkalemia profile compared to spironolactone
- A 2024 individual patient-level meta-analysis of >13,000 patients confirmed MRAs reduce CV death/HF hospitalization across the full EF spectrum
- 2025 CCS/CHFS and JCS/JHFS guidelines now include MRA recommendations for symptomatic HFpEF/HFmrEF patients
- Finerenone is increasingly considered the second pillar alongside SGLT2 inhibitors
Note: Spironolactone (TOPCAT trial) failed its primary endpoint but reduced HF hospitalizations; regional differences in trial validity remain debated.
3. GLP-1 Receptor Agonists (Obesity-related HFpEF)
Two major programs reported in 2024:
- STEP-HFpEF (semaglutide): Improved KCCQ symptoms, physical function, exercise capacity, and weight in obese HFpEF (BMI ≥ 30). Pooled analysis showed reduced CV death/HF events.
- SUMMIT (tirzepatide, dual GLP-1/GIP agonist): Reduced CV death or worsening HF by 38% (HR 0.62, CI 0.41-0.95) in obese HFpEF - moving beyond QOL improvement to hard CV outcomes
The 2025 CCS/CHFS guidelines recommend GLP-1 RA-based drugs for symptomatic HFpEF with LVEF ≥ 45% and BMI ≥ 30 kg/m². This is currently not in ESC/AHA 2022 guidelines but expected to be incorporated in upcoming updates.
4. Sacubitril-Valsartan (ARNi)
- PARAGON-HF: 13% relative reduction in CV death + HF hospitalizations - did not reach significance (p=0.06)
- Subgroup benefit in women and those with LVEF below the median (57%) or EF 40-60% range (HFmrEF overlap)
- PARAGLIDE-HF: Reduced NT-proBNP; benefit mainly in EF ≤ 60%
- FDA-approved in the US for HF across all EF ranges, with acknowledged greatest benefit in reduced/mildly reduced EF
- Consider in LVEF 40-60% (HFmrEF) more than true HFpEF (LVEF > 60%)
Comorbidity Management (Always Required)
| Comorbidity | Target/Approach |
|---|---|
| Hypertension | BP < 130/80 mmHg; meta-analysis (2025) suggests SBP < 130 beneficial |
| Atrial fibrillation | Rate or rhythm control; avoid tachycardia |
| Obesity | GLP-1 agonists, caloric restriction, structured exercise |
| Diabetes | SGLT2 inhibitors address both |
| Iron deficiency | IV iron repletion |
| Sleep apnea | CPAP |
| Congestion | Diuretics (loop diuretics) - symptom control only, no mortality benefit |
Drugs That Do NOT Work in HFpEF
| Drug | Trial | Result |
|---|---|---|
| ACE inhibitors | PEP-CHF | No sustained benefit |
| ARBs (irbesartan) | I-PRESERVE | No benefit |
| ARBs (candesartan) | CHARM-Preserved | Reduced HF admissions only |
| Beta-blockers | SENIORS subgroup | No significant benefit |
| Digoxin | DIG Ancillary | No mortality benefit |
| PDE-5 inhibitors (sildenafil) | RELAX | Ineffective |
| Spironolactone | TOPCAT | Primary endpoint missed |
2026 Horizon: Ongoing Trials
- HERMES: Ziltivekimab (IL-6 inhibitor) in HFpEF + elevated CRP - targets inflammation
- MARITIME-HF: Maridebart cafraglutide (MariTide, anti-GIP/GLP-1) + obesity HFpEF
- FINALITY-HF: Finerenone in HFrEF patients intolerant of steroidal MRAs
Summary: Recommended Drug Hierarchy (2025-2026)
- SGLT2 inhibitors (empagliflozin/dapagliflozin) - Class I for all HFpEF regardless of diabetes
- Finerenone (nonsteroidal MRA) - strong emerging evidence; now in 2025 Canadian and Japanese guidelines; ESC/AHA update expected
- GLP-1/GIP agonists (semaglutide, tirzepatide) - recommended in obesity-related HFpEF (BMI ≥ 30)
- Diuretics - for symptom/volume control
- Sacubitril-valsartan - consider in HFmrEF overlap (EF 40-60%), especially women
- Aggressive comorbidity management - BP, AF, diabetes, obesity, sleep apnea
Key references:
- 2023 ESC HF Focused Update - Class I SGLT2 inhibitor recommendation
- Heart Failure Evidence Update 2026 (PMC) - finerenone/incretin evidence synthesis
- Parizad R et al., 2026 systematic review [PMID: 41953528] - comprehensive therapeutic update
- 2024 ACC/AHA HF Performance Measures Update [PMID: 39116212]
- Harrison's Principles of Internal Medicine 22E (2025) - HFpEF chapter
- Braunwald's Heart Disease, 2-Vol Set - HFpEF chapter
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