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Primary Care Physician Dr. Neil S. Skolnik: The PCPs Role in Improving Outcomes for Patients with Chronic Kidney Disease and Heart Failure

Dr. Neil S. Skolnik

Dr. Neil S. Skolnik

Sponsored by AstraZeneca

As a primary care physician (PCP), my goal is to keep my patients healthy, which includes educating them about diseases they may be at risk for and counseling on preventative measures they can take to minimize these risks.

Common conditions I often assess for are chronic kidney disease (CKD) and heart failure (HF), which are typically interconnected.1 People in the US live with multiple chronic diseases such as cardiovascular (CV), diabetes and CKD with 42% of these patients having 2 or more conditions.2 About 40% to 50% of patients with HF also have CKD.1

Due to the link between CKD and HF, the presence of one condition can worsen the prognosis of the other.3 Because of the asymptomatic nature of early-stage disease, many patients are left undiagnosed until their condition becomes severe.4 In the United States, approximately 90% of adults with CKD are unaware they have it, putting those with both CKD and HF at risk for disease progression.3,4

With many patients in the dark about having a chronic condition, it’s important that we, as PCPs, identify these conditions early on and make shared treatment decisions with our patients – in our offices or in collaboration with our specialist colleagues – to provide accessible guideline-recommended treatment options to improve patient outcomes.

Proactive Measures and Treatment Strategies in CKD and HF Management

CKD screening for at-risk patients, with tests such as blood and urine testing, are diagnostic tools that can help detect CKD early, even in the absence of symptoms.5 Screening appropriate individuals is important. For example, in people with diabetes, screening for HF using NT-proBNP and screening for CKD with eGFR and urine albumin-to-creatinine ratio tests should be done.6,7

Once a patient is diagnosed with CKD and HF, we know that initiation of treatment and regular monitoring at the primary care level is important, as well as working together with cardiologists and nephrologists, if needed.8,9 The Kidney Disease: Improving Global Outcomes 2024 Guideline for the Evaluation and Management of CKD (KDIGO 2024 CKD guideline) recommends a proactive approach, noting that appropriate specialty kidney care referral can reduce length of hospital stays and lower 1-year mortality rates.10

A class of drug called sodium-glucose cotransporter-2 inhibitors (SGLT2is) is recommended by the KDIGO 2024 CKD guideline as first-line drug therapy to treat most patients with CKD, including those with HF.10 The guideline recommends treatment with an SGLT2i for patients with T2D and CKD and an eGFR of ≥20 mL/min/1.73 m2. It also recommends the use of SGLT2is for adults with CKD with an eGFR ≥20 mL/min/1.73 m2 and UACR ≥200 mg/g, or adults with CKD and heart failure, irrespective of albuminuria level.

As first-line providers, it’s important that PCPs have meaningful conversations with appropriate patients and specialists about current guideline recommendations and the benefits of SGLT2is to improve outcomes with CKD and HF.

The Benefit of FARXIGA in Managing CKD and HF

FARXIGA® (dapagliflozin) is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, CV death, and hospitalization for heart failure in adults with CKD at the risk of progression.11 FARXIGA remains the only SGLT2i to significantly reduce the risk of mortality in adult patients with CKD.11-16 FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations.11

The DAPA-CKD Phase III trial was a randomized, double-blind, placebo controlled, multicenter trial designed to evaluate the efficacy of FARXIGA 10 mg compared with placebo on renal and CV outcomes of 4,304 adults with CKD with eGFR of 25-75 mL/min/1.73 m2 and UACR level between 200-5000 mg/g.11,17 In DAPA-CKD, FARXIGA demonstrated a 39% relative risk reduction in the primary composite endpoint of sustained ≥50% eGFR decline, end-stage kidney disease or (CV) or renal death compared to placebo (HR 0.61; 95% CI: 0.51-0.72; p<0.0001) in adults with stage 2-4 CKD and albuminuria. FARXIGA also demonstrated a 29% relative risk reduction in the composite of CV death or hospitalization for HF (HR 0.71; 95% CI: 0.55-0.92; p=0.0089). In the secondary endpoint of all-cause mortality, FARXIGA demonstrated a 31% relative risk reduction (HR 0.69; 95% CI: 0.53-0.88; p=0.0035).

Additionally, FARXIGA is indicated to reduce the risk of CV death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure.11 FARXIGA is also the ONLY SGLT2i proven to significantly reduce the risk of CV death in patients with HFrEF.11-16

The DAPA-HF trial was a Phase 3, randomized, placebo-controlled, HF outcomes trial of 4,744 adults with HF and ejection fraction (EF) ≤40%.11,18 The study assessed whether treatment with FARXIGA reduced the risk of CV events over a median follow-up of 18.2 months. In the DAPA-HF trial, FARXIGA significantly reduced the relative risk of the primary composite outcome of CV death, hHF or urgent HF visit by 26% (HR 0.74; 95% CI: 0.65-0.85; p=<0.000).

Additionally, the DELIVER trial was a Phase 3, randomized, placebo-controlled, HF outcomes trial of 6,263 adults with HF and EF >40%.11,19 The study assessed whether FARXIGA reduced the risk of CV events over a median follow-up of 28 months. In this trial, FARXIGA significantly reduced the relative risk of the primary composite outcome of CV death, hHF or urgent HF visit by 18% (HR 0.82; 95% CI: 0.73-0.92 P=0008).

As a primary care physician, I often see patients with both CKD and HF, struggling as their conditions worsen. FARXIGA has been an effective form of treatment for my patients. FARXIGA is contraindicated in patients with a history of serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA. See below for additional Important Safety Information.

Based on the benefit of FARXIGA in slowing the progression of CKD and reducing the risk of CV death and hospitalization for HF in adults with HF, being proactive and introducing treatment in appropriate patients, consistently with guideline recommendations, may result in better outcomes for patients.

Serving as a Patient Advocate to Improve Outcomes in CKD and HF

For patients living with CKD and/or HF, it’s important to help educate our patients on navigating their disease through an often-complex health system.

PCPs can help bridge the gap between specialists by being patient advocates and liaising between specialists to facilitate informed decision-making and ensure patients have access to the right treatment.8-10

Now more than ever, it’s important for PCPs to play an active role in providing patients with support to accessible treatment options. As of January 2024, an authorized generic version of FARXIGA has become available for patients in the United States and Puerto Rico. FARXIGA is now the only SGLT2i available in both a brand and generic form, offering options at the pharmacy for patients.

For more information about FARXIGA, visit https://www.farxiga.com/.

IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin)

Contraindications

History of serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA.

Warnings and Precautions

  • Ketoacidosis: FARXIGA significantly increases the risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus. Type 2 diabetes mellitus and pancreatic disorders are also risk factors. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including FARXIGA. Consider ketone monitoring in patients with type 1 diabetes mellitus and in others at risk for ketoacidosis. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose levels. If suspected, discontinue FARXIGA, evaluate and treat promptly. Withhold FARXIGA, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume FARXIGA when the patient is clinically stable and has resumed oral intake
  • Volume Depletion: FARXIGA can cause intravascular volume depletion, which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including FARXIGA. Patients with impaired renal function (eGFR less than 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 FARXIGA in these patients, assess volume status and renal function. After initiating therapy, monitor for signs and symptoms of hypotension and renal function
  • Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
  • Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
  • Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare but serious, life-threatening cases have been reported in patients with diabetes mellitus receiving SGLT2 inhibitors, including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA
  • Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
  • Most Common Adverse Reactions (≥5%): Female genital mycotic infections, nasopharyngitis, and urinary tract infections.
  • Use in Specific Populations
  • Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters
  • Lactation: FARXIGA is not recommended when breastfeeding

INDICATIONS AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin)

FARXIGA is indicated:

  • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular (CV) disease or multiple CV risk factors
  • to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure
  • to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression

FARXIGA is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.

FARXIGA is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. FARXIGA is likely to be ineffective in this setting based upon its mechanism of action.

FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations.

DOSING

To improve glycemic control in adults and pediatric patients aged 10 years and older with T2D, the recommended starting dose is 5 mg orally once daily. Dose can be increased to 10 mg orally once daily for additional glycemic control.

For other indications in adults, the recommended dose is 10 mg orally once daily.

Please see accompanying US Full Prescribing Information for FARXIGA.

References

  1. Aguilar D. Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease. Circ Heart Fail. 2016;9(7). doi:https://doi.org/10.1161/circheartfailure.116.003316
  2. Benavidez GA, Zahnd WE, Hung P, et al. Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area. Prev Chronic Dis 2024;21:230267. DOI: http://dx.doi.org/10.5888/pcd21.230267.
  3. Shiba N, Shimokawa H. Chronic kidney disease and heart failure—Bidirectional close link and common therapeutic goal. J Cardiol. 2011;57(1):8-17. doi:https://doi.org/10.1016/j.jjcc.2010.09.004
  4. ‌CDC. Chronic Kidney Disease Basics. Chronic Kidney Disease. Published March 26, 2024. https://www.cdc.gov/kidney-disease/about/index.html. Accessed August 16, 2024.
  5. Shlipak MG, Tummalapalli SL, Boulware LE, et al. The Case for Early Identification and Intervention of Chronic Kidney Disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020;99(1):34-47. doi:https://doi.org/10.1016/j.kint.2020.10.012
  6. American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S179-S218. doi:10.2337/dc24-S010
  7. American Diabetes Association Professional Practice Committee. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S219-S230. doi:10.2337/dc24-S011
  8. Greer RC, Liu Y, Cavanaugh K, et al. Primary Care Physicians' Perceived Barriers to Nephrology Referral and Co-management of Patients with CKD: a Qualitative Study. J Gen Intern Med. 2019;34(7):1228-1235. doi:10.1007/s11606-019-04975-
  9. Wójcik C, Shapiro MD. Bridging the Gap Between Cardiology and Family Medicine. Circulation. 2019;140(9):709-711. doi:https://doi.org/10.1161/circulationaha.119.040151
  10. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.; 2024. https://kdigo.org/wp-content/uploads/2024/03/KDIGO-2024-CKD-Guideline.pdf
  11. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024‌
  12. Jardiance® (empagliflozin) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2023.
  13. Invokana® (canagliflozin) [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2023.
  14. Steglatro® (ertugliflozin) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2024.
  15. Brenzavvy® (bexagliflozin) [package insert]. Marlborough, MA: TheracosBio, LLC; 2023.
  16. Inpefa® (sotagliflozin) [package insert]. The Woodlands, TX: Lexicon Pharmaceuticals, Inc; 2024.
  17. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
  18. McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
  19. Solomon SD, McMurray JJV, Claggett B, et al; DELIVER Trial Committees and Investigators. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098 and Supplementary Appendix
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