HF management guidelines recommend SGLT inhibitors as foundational therapy regardless of LVEF1

INPEFA® is featured in clinical practice HF guidelines1‑3

The clinical benefits of INPEFA for patients with HF, as demonstrated in the SOLOIST‑WHF study, were featured in the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure and were carried through in the 2023 ACC Expert Consensus Decision Pathway on Management of HFpEF and 2024 ACC Expert Consensus Decision Pathway for Treatment of HF with HFrEF1‑3

2022 AHA/ACC/HFSA HF
Guideline Summary

  • HFrEF1,2

    2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF

    • Recognizes SGLT inhibitors (including SGLT1/2 or SGLT2 inhibitors) as a core therapy in the 4 pillars of medical care for HFrEF
    • Reports that in SOLOIST‑WHF, INPEFA reduced HF events among individuals with T2DM hospitalized for HF who were treated during or soon after hospitalization

    2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

    • Recommends SGLT inhibitors as class 1A GDMT for HFrEF
    • Reports that SOLOIST‑WHF, which evaluated INPEFA in patients with worsening HF, demonstrated the benefits of in‑hospital initiation of GDMT in patients with worsening HF

  • HFmrEF1

    2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

    • Recommends SGLT inhibitors as class 2A GDMT that can be beneficial in decreasing HF hospitalizations and CV mortality

  • HFpEF2,3

    2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure with Preserved Ejection Fraction

    • Establishes SGLT inhibitors as the foundational therapy for HFpEF
    • Asserts that INPEFA significantly reduced the risk of CV death, hospitalization for HF, and urgent HF visit when compared to placebo as evaluated in SOLOIST‑WHF

    2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure

    • Recommends SGLT inhibitors as class 2A GDMT for HFpEF

INPEFA is the only SGLT inhibitor

that has stated in its label that it can be
initiated as soon as the patient is stabilized.4‑8

2022 AHA/ACC/HFSA Guideline for Management of HF1

features SOLOIST‑WHF, which studied INPEFA compared to placebo for the management of HF, as evidence of the benefits of:

  • initiation in hospital or shortly after discharge (outpatient care setting)
  • an SGLT inhibitor for patients with worsening HF

ACC=American College of Cardiology; AHA=American Heart Association; CV=cardiovascular; GDMT=guideline‑directed medical therapy; HF=heart failure; HFmrEF=heart failure with mid‑range ejection fraction; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HFSA=Heart Failure Society of America; LVEF=left ventricular ejection fraction; SGLT1=sodium‑glucose cotransporter 1; SGLT2=sodium‑glucose cotransporter 2; T2DM=type 2 diabetes mellitus; WHF=worsening heart failure.

The risk of CV events for patients with HF is underestimated compared to the risk for patients with ASCVD*12

The absolute rate of CV events† for patients with HFrEF who are considered ″stable″ (≥~10%) far exceeds that for patients with ASCVD* who have had multiple events and are considered “very high risk” (≤7%)12

Risk of CV events in patients with HF vs. ASCVDRisk of CV events in patients with HF vs. ASCVD

Figure adapted from Greene et al.12

*MI or ischemic stroke.
†CV death or HF hospitalization.

A first‑line option1‑4

Starting INPEFA first line could be key to managing your patients with HF.1

ASCVD=atherosclerotic cardiovascular disease; EF=ejection fraction; MI=myocardial infarction; NYHA=New York Heart Association.

Explore Soloist‑WHF STUDY

References:

1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033]. Circulation. 2022;145(18):e895‑e1032. doi:10.1161/CIR.0000000000001063 2. Maddox, T, Januzzi, J, Allen, L. et al. 2024 ACC Expert consensus decision pathway for treatment of heart failure with reduced ejection fraction: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol. 2024;83(15):1444‑1488. doi.org/10.1016/j.jacc.2023.12.024 3. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2023;81(18):1835‑1878. doi:10.1016/j.jacc.2023.03.393 4. INPEFA [prescribing information]. Lexicon Pharmaceuticals, Inc.; 2024. 5. INVOKANA [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2023. 6. STEGLATRO [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc; 2022. 7. JARDIANCE (empagliflozin) [package insert]. Boehringer Ingelheim Pharmaceuticals; 2023. 8. FARXIGA (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. 9. Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117‑128. doi:10.1056/NEJMoa2030183 10. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089‑1098. doi:10.1056/NEJMoa2206286 11. Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568‑574. doi:10.1038/s41591‑021‑01659‑1 12. Greene SJ, Bauersachs J, Brugts JJ, et. al. Worsening heart failure: nomenclature, epidemiology, and future directions. J Am Coll Cardiol. 2023;81(4):413‑424. doi:10.1016/j.jacc.2022.11.023

Important Safety Information

Dosing:

Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA. INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge.

Contraindications:

INPEFA is contraindicated in patients with hypersensitivity to any component.

Warnings and Precautions

  • Ketoacidosis:

    INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM). Type 2 diabetes mellitus (T2DM) and pancreatic disorders are also risk factors. The risk of ketoacidosis may be greater with higher doses. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors. Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis, and educate patients on the signs/symptoms of ketoacidosis. Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis.

    Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level. If suspected, discontinue INPEFA, evaluate, and treat promptly. Monitor patients for resolution of ketoacidosis before restarting INPEFA.

  • Volume Depletion:

    INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy.

  • Urosepsis and Pyelonephritis:

    Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections. Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly.

  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues:

    Insulin and insulin secretagogues are known to cause hypoglycemia. INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA.

  • Necrotizing Fasciitis of the Perineum (Fournier's Gangrene):

    Reports of Fournier's Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure.

  • Genital Mycotic Infections:

    INPEFA increases the risk of genital mycotic infections. Monitor and treat as appropriate.

  • Urinary Glucose Test and 1,5‑anhydroglucitol (1,5‑AG) Assay:

    These are not reliable for patients taking SGLT2 inhibitors. Use alternative testing methods to monitor glucose levels.

Common Adverse Reactions:

The most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia.

Drug Interactions:

  • Digoxin:

    Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg.

  • Uridine 5'‑diphospho‑glucuronosyltransferase (UGT) Inducer:

    The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin.

  • Lithium:

    Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes.

Use in Specific Populations:

  • Pregnancy and Lactation:

    INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding.

  • Geriatric Use:

    No INPEFA dosage change is recommended based on age. No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.

  • Renal Impairment:

    INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR < 60 mL/min/1.73 m2. The safety profile of INPEFA across eGFR subgroups in these studies was consistent with the known safety profile. There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR < 30 mL/min/1.73 m2 relative to the overall safety population. Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis. After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis.

  • Hepatic Impairment:

    INPEFA is not recommended in patients with moderate or severe hepatic impairment.

Indication

INPEFA® is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with:

  • heart failure or
  • type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors

Please see full Prescribing Information and Patient Medication Guide.