Finerenone Elevated, GLP-1 Therapies Expanded in Updated ACC Consensus for HFpEF

 July 2026 Cardiology Update

Heart failure with preserved ejection fraction (HFpEF) now accounts for more than half of all heart failure cases, and treatment options continue to expand. In its updated 2026 Expert Consensus Decision Pathway for HFpEF (Kittleson et al., JACC 2026), the American College of Cardiology (ACC) emphasizes a modern treatment strategy built around SGLT2 inhibitors, finerenone, and incretin-based therapies — while highlighting the growing overlap between HFpEF and cardiovascular-kidney-metabolic (CKM) syndrome.


Diagnosis First

The ACC stresses that clinicians must first confirm that symptoms such as dyspnea, edema, and exercise intolerance truly result from HFpEF. Alternative diagnoses — including kidney disease, liver disease, valvular heart disease, hypertrophic cardiomyopathy, and cardiac amyloidosis — should be excluded before initiating treatment. The diagnosis of HFpEF remains more challenging than HFrEF because cardinal physical examination findings of elevated jugular venous pressure or pulmonary congestion may not be evident at rest.

The H2FPEF score (range 0–9) integrates clinical and echocardiographic variables — obesity, hypertension requiring ≥2 medications, atrial fibrillation, pulmonary hypertension, age >60, and elevated E/e' — to estimate HFpEF probability. A score >5 indicates more than 95% probability of HFpEF, while a score of 0–1 indicates less than 25% probability. Intermediate scores warrant exercise stress echocardiography or invasive hemodynamic testing.

Importantly, natriuretic peptide thresholds require adjustment for obesity: approximately 20% of HFpEF patients with obesity have normal natriuretic peptide levels. Recent evidence suggests a rule-out NT-proBNP threshold of <50 pg/mL (rather than <125 pg/mL) improves sensitivity, particularly in patients with BMI ≥35 kg/m².


SGLT2 Inhibitors Remain Foundational

The updated pathway provides its strongest endorsement yet for SGLT2 inhibitors, supported by the landmark EMPEROR-Preserved and DELIVER trials. In EMPEROR-Preserved, empagliflozin 10 mg daily reduced the composite of cardiovascular death or hospitalization for heart failure by 21% (HR 0.79; 95% CI 0.69–0.90; P<0.001) in 5,988 patients with LVEF >40%. In DELIVER, dapagliflozin 10 mg daily achieved an 18% reduction in the same composite endpoint (HR 0.82; 95% CI 0.73–0.92; P<0.001) in 6,263 patients. Benefits were consistent regardless of diabetes status, and dapagliflozin demonstrated statistically significant reductions within just two weeks of treatment initiation.

A meta-analysis of nine randomized controlled trials involving over 20,000 patients confirmed that SGLT2 inhibitors significantly reduce the risk of cardiovascular death or heart failure hospitalization (HR 0.83; 95% CI 0.76–0.90) and heart failure hospitalization alone (HR 0.75; 95% CI 0.68–0.84) in HFpEF. These agents should be initiated in all patients with HFpEF lacking contraindications and can be used with eGFR ≥20 mL/min/1.73 m².


Finerenone Moves Into the Spotlight

A major update is the inclusion of finerenone (Kerendia) as a preferred nonsteroidal mineralocorticoid receptor antagonist (MRA). In the FINEARTS-HF trial, 6,001 patients with heart failure and LVEF ≥40% were randomized to finerenone (maximum dose 20–40 mg daily) or placebo. Over a median follow-up of 32 months, finerenone reduced the composite of total worsening heart failure events and cardiovascular death by 16% (rate ratio 0.84; 95% CI 0.74–0.95; P=0.007), driven primarily by an 18% reduction in worsening heart failure events (rate ratio 0.82; 95% CI 0.71–0.94; P=0.006). This benefit was consistent across the full spectrum of ejection fractions, from LVEF <50% through ≥60%, and across all prespecified subgroups — including patients with and without diabetes, CKD, and concurrent SGLT2 inhibitor or GLP-1 receptor agonist use.

Finerenone now carries an FDA-approved indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure and LVEF ≥40%. Compared with traditional steroidal MRAs — for which evidence in HFpEF remains limited to post-hoc analyses (Class 2b in current U.S. guidelines) — finerenone offers proven cardiovascular and renal benefits with a more favorable hyperkalemia profile, making it an increasingly important component of optimal HFpEF therapy.

A cross-trial analysis by Vaduganathan et al. (Nature Medicine, 2026) estimated that combined SGLT2 inhibitor + finerenone therapy reduces the risk of cardiovascular death or first worsening heart failure event by 31% (HR 0.69; 95% CI 0.59–0.81). In patients with LVEF <60%, the addition of sacubitril/valsartan (ARNI) to this combination yielded a 39% reduction (HR 0.61; 95% CI 0.48–0.77) — translating to an estimated 3.6 to 4.9 additional years free from cardiovascular death or heart failure events in a 65-year-old patient. These gains were meaningful across a broad age range, from 55 to 85 years.


GLP-1 and GIP/GLP-1 Agonists for Obesity-Related HFpEF

Recognizing the strong relationship between obesity and HFpEF, the ACC now emphasizes the use of incretin-based therapies. Both semaglutide and tirzepatide have demonstrated significant improvements in weight loss, exercise capacity, symptoms, and quality of life — and for patients with overweight or obesity, these therapies target a major driver of HFpEF pathophysiology rather than simply addressing congestion.

In the STEP-HFpEF program, 1,145 patients with HFpEF (LVEF ≥45%) and BMI ≥30 kg/m² were randomized to semaglutide 2.4 mg weekly or placebo. Semaglutide significantly improved quality of life (KCCQ scores), 6-minute walk distance, and body weight, with a pooled analysis showing a 73% reduction in time to first heart failure event (HR 0.27; 95% CI 0.12–0.56).

In the SUMMIT trial, 731 patients with HFpEF (LVEF ≥50%) and obesity were randomized to tirzepatide (target 15 mg subcutaneously weekly) or placebo over a median of 104 weeks. Tirzepatide reduced the composite of cardiovascular death or worsening heart failure by 38% (HR 0.62; 95% CI 0.41–0.95; P=0.026), with a 56% reduction in worsening heart failure resulting in hospitalization (HR 0.44; 95% CI 0.22–0.87). Health status improved by 6.9 points on the KCCQ-CSS (P<0.001), and 6-minute walk distance increased by 18.3 meters (P<0.001). Mechanistically, tirzepatide reduced systolic blood pressure by 5 mmHg, estimated blood volume by 0.58 liters, and C-reactive protein by 37%, while preserving estimated glomerular filtration rate — suggesting benefits extend beyond weight loss to include volume-pressure unloading and anti-inflammatory effects.

A large real-world cohort study of nearly 100,000 patients with cardiometabolic HFpEF (JAMA, 2025) confirmed these findings, demonstrating more than 40% risk reduction for the composite of heart failure hospitalization or all-cause mortality with both semaglutide (HR 0.58) and tirzepatide (HR 0.42) compared with sitagliptin. In head-to-head comparison, tirzepatide showed no meaningful advantage over semaglutide (HR 0.86; 95% CI 0.70–1.06).


HFpEF and CKM Syndrome: An Integrated Approach

One of the most important themes of the updated consensus is the recognition that HFpEF often exists within the broader framework of cardiovascular-kidney-metabolic (CKM) syndrome. The 2026 AHA/ACC/ADA/ASN CKM Guideline defines CKM syndrome as a progressive spectrum from excess adiposity (stage 1) through metabolic risk factors and CKD (stage 2), subclinical CVD (stage 3), to clinical CVD including heart failure (stage 4).

Many HFpEF patients simultaneously have:

- Obesity

- Type 2 diabetes

- Chronic kidney disease

- Hypertension

- Coronary artery disease

Importantly, therapies such as SGLT2 inhibitors, finerenone, semaglutide, and tirzepatide provide benefits that extend beyond heart failure, improving cardiovascular, renal, and metabolic health simultaneously. For patients with HFmrEF or HFpEF within the CKM framework, first-line treatment includes SGLT2 inhibitors and diuretics for congestion, with emerging data supporting finerenone as a key addition. Beta-blockers are not recommended for HFpEF in the absence of secondary indications (e.g., atrial fibrillation, symptomatic coronary artery disease).


Practical Clinical Takeaways

The ACC's updated roadmap for HFpEF recommends:

✅ Confirming the diagnosis and excluding mimics such as amyloidosis, HCM, and valvular disease

✅ Initiating SGLT2 inhibitors (empagliflozin or dapagliflozin) in all eligible patients

✅ Adding finerenone when appropriate, particularly in patients with concomitant CKD or diabetes

✅ Considering GLP-1 receptor agonists (semaglutide) or GIP/GLP-1 agonists (tirzepatide) in patients with obesity (BMI ≥30 kg/m²)

✅ Aggressively treating comorbidities including atrial fibrillation, hypertension, diabetes, chronic kidney disease, and sleep apnea

✅ Managing HFpEF through the broader lens of CKM syndrome


Bottom Line

HFpEF is no longer a therapeutic desert. Evidence from EMPEROR-Preserved, DELIVER, FINEARTS-HF, STEP-HFpEF, and SUMMIT has transformed management. The combination of SGLT2 inhibitors, finerenone, and incretin-based therapies offers clinicians an expanding arsenal of treatments that improve outcomes while addressing the interconnected cardiovascular, kidney, and metabolic abnormalities that characterize modern HFpEF. A cross-trial analysis projects that early combination therapy with SGLT2 inhibitors and finerenone — with the addition of ARNI in selected patients — could afford patients nearly 4 to 5 additional years free from cardiovascular death or heart failure events.


Key References

- 2026 ACC Expert Consensus Decision Pathway for HFpEF (Kittleson et al., JACC 2026)

- EMPEROR-Preserved (Anker et al., NEJM 2021)

- DELIVER (Solomon et al., NEJM 2022)

- FINEARTS-HF (Solomon et al., NEJM 2024)

- STEP-HFpEF (Kosiborod et al., NEJM 2023)

- SUMMIT (Packer et al., NEJM 2025)

- Lifetime Benefits of Comprehensive Medical Therapy (Vaduganathan et al., Nature Medicine 2026)

- 2026 AHA/ACC/ADA/ASN CKM Guideline (Ndumele et al., Circulation 2026)