A 75-year-old Caucasian woman with a 10-year history of type-2 diabetes mellitus, and a 3-year history of ischemic cardiomyopathy following an anterior myocardial infarction presents for office evaluation of class II heart failure symptoms. Her review of systems (ROS) is negative for diabetic ketoacidosis, peripheral artery disease, or genital mycotic infections. Current medications include metformin, sitagliptin, enalapril, and carvedilol. Her blood pressure is 130/85mmHg, pulse 70 beats per minute, and exam notable for a diffuse and laterally displaced point of maximal impulse (PMI), soft S1 S2, no S3 or murmurs, and 1+ pedal edema. An electrocardiogram (ECG) reveals normal sinus rhythm (NSR), left ventricular hypertrophy (LVH), and Q-waves anteriorly. An echocardiogram demonstrates left ventricular ejection fraction (LVEF)=35%, and anterior hypokinesis. Laboratories: Cr=1.7, HbA1C=7.2%, BNP=310 pg/ml, urine albumin/creatinine ratio=410 mg/g.
Which of the following therapeutic changes will reduce this patient's risks for heart failure hospitalization, cardiovascular death, and progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) or renal death?
The correct answer is: C. Discontinue sitagliptin and start dapagliflozin
Sitagliptin has not been associated with improved renal or cardiovascular outcomes. Dapagliflozin in the DAPA-HF trial was associated with 26% relative risk reduction (p<0.001), in heart failure hospitalization and death.1 In the DAPA-CKD trial, dapagliflozin reduced the primary outcome of eGFR decline ≥50%, end-stage kidney disease (ESKD), or kidney/cardiovascular death by 39% (p<0.001).2 This patient demonstrates reasonable glycemic control thus an exchange of glycemic lowering therapies is reasonable to minimize risk of hypoglycemia.
Digoxin was associated with reductions in heart failure hospitalization in the DIG-HF trial but has a limited therapeutic window in moderate to severe CKD and is not associated with improved renal outcomes.3
Furosemide may reduce edema but has not been shown to improve renal or cardiac outcomes.
Changing from enalapril to valsartan/sacubitril may reduce the risk of heart failure hospitalization and death by 20% but has not been shown to reduce progression of CKD to ESRD or renal death.4
Long-acting nitrates/hydralazine have not been shown to reduce progression of CKD to ESRD or renal death, and are associated with common adverse effects including headache, orthostasis, and drug-induced lupus.5
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019;381:1995-2008.
McMurray JJV, Wheeler DC, Stefánsson BV, et al. Effect of dapagliflozin on clinical outcomes in patients with chronic kidney disease, with and without cardiovascular disease. Circulation 2021;143:438-48.
Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-33.
McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351:2049-57.