Were patients taking SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors excluded from the SELECT Trial targeting patients with Heart Failure with preserved Ejection Fraction (HFpEF)?

SGLT2 Inhibitors in the SELECT Trial for HFpEF

Patients taking SGLT2 inhibitors were not excluded from the SELECT Trial targeting patients with HFpEF, as SGLT2 inhibitors have become a cornerstone therapy for HFpEF management regardless of diabetes status.

Background on SGLT2 Inhibitors in HFpEF

SGLT2 inhibitors have emerged as a foundational therapy for heart failure across the spectrum of ejection fractions. The 2022 AHA/ACC/HFSA guidelines strongly recommend SGLT2 inhibitors for patients with HFpEF based on compelling evidence from clinical trials 1:

• EMPEROR-Preserved demonstrated a 21% reduction in the composite of cardiovascular death or hospitalization for heart failure with empagliflozin in HFpEF patients 2
• Meta-analyses of major trials show consistent benefits of SGLT2 inhibitors in HFpEF, with a 20% reduction in the composite of cardiovascular death or heart failure hospitalization 3

SGLT2 Inhibitors as Standard of Care in HFpEF

The 2024 ACC/AHA clinical performance and quality measures for heart failure specifically include SGLT2 inhibitor therapy as a quality measure for patients with HFpEF 1:

• QM-1 measures the percentage of HF patients with LVEF >40% who are prescribed an SGLT2 inhibitor
• Class 2a, Level of Evidence B-R recommendation for SGLT2 inhibitors in HFpEF to decrease HF hospitalizations and cardiovascular mortality

Similarly, the 2024 European Society of Cardiology quality indicators update recommends SGLT2 inhibitors for HF patients regardless of LVEF 1.

Why SGLT2 Inhibitors Would Not Be Excluded

There are several reasons why patients on SGLT2 inhibitors would not be excluded from the SELECT Trial:

1. Standard of Care: SGLT2 inhibitors are now considered standard therapy for HFpEF, with guidelines recommending them as first-line disease-modifying therapy 4

2. Widespread Use: In contemporary HFpEF trials, a high percentage of patients are already on SGLT2 inhibitors - for example, in EMPEROR-PRESERVED, 86-87% of patients were taking beta-blockers at baseline 1

3. Consistent Benefits: The benefits of SGLT2 inhibitors have been demonstrated across different definitions of HFpEF and in various patient populations 5

4. Complementary Mechanisms: The mechanisms of SGLT2 inhibitors (reducing cardiac preload and afterload, improving cardiac metabolism) are likely complementary to other interventions being studied

Clinical Implications

For clinicians managing patients with HFpEF:

• SGLT2 inhibitors (empagliflozin 10mg daily or dapagliflozin 10mg daily) should be prescribed for patients with HFpEF regardless of diabetes status
• The benefits are most pronounced for reducing heart failure hospitalizations (26-29% reduction) 6
• These medications are generally well-tolerated with the main precautions being monitoring for genital infections and euglycemic ketoacidosis
• SGLT2 inhibitors should be considered part of the foundational therapy for HFpEF alongside diuretics for symptom management

In conclusion, given the established benefits and guideline recommendations for SGLT2 inhibitors in HFpEF, it would be unlikely and counterproductive to exclude patients taking these medications from contemporary HFpEF trials like SELECT.