What class of medication is likely to reduce the progression of chronic kidney disease (CKD), death from cardiovascular causes, and hospitalization for heart failure with mid-range ejection fraction in a patient with hypertension, hyperlipidemia, and impaired renal function, currently treated with amlodipine, furosemide, potassium chloride, and atorvastatin?

From the Guidelines

The SGLT-2 inhibitor is likely to reduce the progression of kidney disease, death from cardiovascular causes, and hospitalization for heart failure in this patient. SGLT-2 inhibitors like empagliflozin, dapagliflozin, and canagliflozin have demonstrated significant cardiorenal protective effects in patients with heart failure, regardless of diabetes status, as shown in the most recent study 1. These medications work by blocking glucose reabsorption in the proximal tubule of the kidney, leading to increased urinary glucose excretion. Beyond glycemic effects, they provide multiple benefits including reduced preload and afterload, decreased inflammation, improved energy metabolism in cardiac cells, and renoprotection through reduced hyperfiltration. For this 68-year-old patient with heart failure with mid-range ejection fraction, chronic kidney disease, hypertension, and hyperlipidemia, adding an SGLT-2 inhibitor would be appropriate given his eGFR of 45, which is still within the range where these medications can be initiated.

Some key benefits of SGLT-2 inhibitors include:

• Reduced risk of incident or worsening nephropathy by 39% with empagliflozin 1
• Reduced risk of progression of albuminuria by 27% with canagliflozin 1
• Reduced risk of new or worsening nephropathy by 22% with liraglutide, although GLP-1 agonists have shown benefits primarily in diabetic patients 1
• Reduced risk of cardiovascular death or heart failure hospitalization by 31% with SGLT-2 inhibitors 1

While GLP-1 agonists have shown cardiovascular benefits primarily in diabetic patients, SGLT-2 inhibitors have demonstrated broader benefits in non-diabetic patients with heart failure and kidney disease, making them the preferred choice in this clinical scenario, as supported by the most recent and highest quality study 1.

From the FDA Drug Label

The primary composite endpoint in the CREDENCE trial was the time to first occurrence of ESKD (defined as an eGFR < 15 mL/min/1. 73 m 2, initiation of chronic dialysis or renal transplant), doubling of serum creatinine, and renal or CV death. Canagliflozin 100 mg significantly reduced the risk of the primary composite endpoint based on a time-to-event analysis [HR: 0.70; 95% CI: 0.59,0.82; p<0. 0001] Canagliflozin 100 mg also significantly reduced the risk of hospitalization for heart failure [HR: 0.61; 95% CI: 0.47 to 0.80; p<0. 001]

The answer is SGLT-2 inhibitor.

• The SGLT-2 inhibitor class of drugs, as represented by canagliflozin in the CREDENCE trial, has been shown to reduce the progression of kidney disease, death from cardiovascular causes, and hospitalization for heart failure 2.
• Key benefits include:
  • Reduced risk of end-stage kidney disease (ESKD)
  • Reduced risk of doubling of serum creatinine
  • Reduced risk of cardiovascular death
  • Reduced risk of hospitalization for heart failure

From the Research

Classes of Drugs for Reducing Kidney Disease Progression, Death from Cardiovascular Causes, and Hospitalization for Heart Failure

• SGLT-2 inhibitors have been shown to mitigate the risks of cardiovascular and renal complications in patients with type 2 diabetes and CV risk factors or CV disease 3, 4.
• The use of SGLT-2 inhibitors is expected to increase, suggesting that a growing number of patients will present to the emergency departments with these drugs, and they are beneficial in heart failure with reduced ejection fraction and chronic kidney disease, including in patients without diabetes 5, 6.
• SGLT-2 inhibitors are the most beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease who need further hemoglobin A1c reduction 7.
• The exact mechanisms for how SGLT-2 inhibitors are beneficial in heart failure are unknown, but current hypotheses include multiple metabolic and hemodynamic mechanisms 5.

Key Findings

• SGLT-2 inhibitors have been associated with significant reductions in the risks of major adverse CV events, hospitalization for heart failure, and kidney disease progression 3, 4.
• SGLT-2 inhibitors are effective at lowering body weight in obese individuals and decreasing systolic blood pressure 7.
• Dual SGLT1/SGLT2 inhibitors are currently being investigated as possibly the first oral medication for type 1 diabetes 7.

Applicability to the Patient

• Although the patient is nondiabetic, SGLT-2 inhibitors have shown benefits in patients with heart failure and chronic kidney disease, regardless of diabetes status 5, 6.
• The patient's history of heart failure with mid-range ejection fraction, chronic kidney disease, hypertension, and hyperlipidemia may benefit from the use of SGLT-2 inhibitors 3, 4, 5, 6, 7.