A 57-year-old woman is seen during a routine follow-up visit for heart failure. She has a 5-year history of ischemic cardiomyopathy with an ejection fraction of 38%. She also has a 15-year history of type 2 diabetes mellitus and diabetic kidney disease. She has had no hospitalizations. Medications are aspirin, atorvastatin, valsartan-sacubitril, metoprolol succinate, and metformin.
Physical examination, including vital signs, is unremarkable.
Laboratory studies show an elevated B-type natriuretic peptide level, a hemoglobin A1c level of 7.0%, a serum creatinine level of 1.5 mg/dL (132.6 μmol/L), and an estimated glomerular filtration rate of 50 mL/min/1.73 m2.
Which of the following is the most appropriate additional treatment?
MKSAP Answer and Critique
The correct answer is A. Dapagliflozin. This item is available to MKSAP 19 subscribers as item 117 in the Cardiology section. More information about MKSAP is online.
The most appropriate treatment is to add dapagliflozin (Option A). This patient has heart failure, type 2 diabetes mellitus, and kidney disease. Evidence shows that the sodium-glucose cotransporter 2 (SGLT2) inhibitors dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin are associated with a reduction in cardiovascular death or hospitalization for heart failure in patients with type 2 diabetes, and dapagliflozin and empagliflozin are effective in patients without diabetes. In addition, for patients with type 2 diabetes, an SGLT2 inhibitor reduces progression of diabetic kidney disease. SGLT2 inhibitors should not be used in patients with type 1 diabetes, increased risk for type 2 diabetic ketoacidosis, or rapidly declining or changing kidney function.
Glimepiride (Option B) is a second-generation sulfonylurea. Although the results of many studies have been inconclusive, it seems that the second-generation agents most likely do not have any adverse cardiac effects but also have no cardiac benefit.
Among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease (ASCVD) or established kidney disease, the American Diabetes Association and the American College of Cardiology recommend an SGLT2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit. In patients with type 2 diabetes and ASCVD, liraglutide, semaglutide (injectable), and dulaglutide have been shown to decrease cardiovascular death. However, liraglutide (Option C) has no effect on heart failure outcomes in patients with established heart failure.
Saxagliptin (Option D) is a dipeptidyl peptidase-4 inhibitor, a class of drug that has been shown to have no difference in cardiovascular outcomes compared with placebo. However, depending on the study, there was either a trend toward more heart failure hospitalizations (saxagliptin) or an increased incidence of heart failure (alogliptin). Because of this increased incidence of heart failure hospitalizations, adding saxagliptin as a second-line agent would not be appropriate.
- Sodium-glucose cotransporter 2 inhibitors reduce risk for worsening heart failure and cardiovascular death in patients with heart failure with reduced ejection fraction with or without type 2 diabetes mellitus.
- Among patients with type 2 diabetes mellitus who have established atherosclerotic cardiovascular disease or established kidney disease, a sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular disease benefit is recommended.