A 65-year-old man with a history of chronic heart failure with reduced ejection fraction (HFrEF) is admitted with exertional shortness of breath, paroxysmal nocturnal dyspnea, bendopnea, and weight gain. At the time of admission, his eGFR is 65 mL/min/1.73 m2 and an N-terminal pro-B-type natriuretic peptide (NT-proBNP) is 1,200 pg/mL.
Prior medical history includes the following:
HFrEF:
Echocardiogram (6 months prior): left ventricular ejection fraction (LVEF) 25%, normal right ventricular function, and no significant valvular dysfunction.
CRT-D implanted 2 years prior for primary prevention and a left bundle branch block with a QRS width > 150 ms.
Home medications include carvedilol, spironolactone, and sacubitril/valsartan.
Type 2 diabetes mellitus:
Most recent HbA1c of 7.4% when measured 3 months ago.
Hypertension
Stage 2 chronic kidney disease
He is diagnosed with acutely decompensated heart failure and started on IV furosemide. After 3 days of diuresis, his symptoms have markedly improved and his weight has returned to baseline. He is transitioned back to an oral diuretic regimen.
Relevant labs on the day of transition to oral diuretics include:
Sodium 134 mEq/L
Potassium 4.1 mEq/L
eGFR 60 mL/min/1.73 m2
His blood pressure on the day of transition to oral diuretics is 110/70 mmHg, his heart rate is 65 beats per minute, and he required no supplemental oxygen throughout the admission.
Current in-hospital medications:
Sacubitril/valsartan 97/103 mg twice daily
Carvedilol 25 mg twice daily
Spironolactone 25 mg once daily
Bumetanide 2 mg once daily
Metformin 1,000 mg twice daily
Prior to discharge from the hospital, the addition of which of the following medications to his current regimen would decrease his risk of cardiovascular death and future heart failure hospitalization or urgent visit for heart failure?
Show Answer
The correct answer is: C. Add sotagliflozin 200 mg once daily and titrate to 400 mg daily, as tolerated.
The addition of sotagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor with mild gastrointestinal SGLT1 inhibition, confers a significant reduction in the risk of cardiovascular death and hospitalizations or urgent visits for heart failure over a median follow-up period of 9 months.
SGLT2 inhibitors have emerged as the fourth class of drugs that reduce cardiovascular mortality and heart failure hospitalizations in stable HFrEF patients with and without diabetes. Both dapagliflozin1 and empagliflozin2 have shown significant reductions in death and worsening heart failure when added to standard guideline-directed medical therapy for HFrEF. Chronic kidney disease is frequently co-morbid in patients with heart failure and the addition of dapagliflozin to patients with chronic kidney disease3 has also been shown to reduce the risk of a composite endpoint consisting of sustained decline of the estimated glomerular filtration rate of at least 50%, end-stage kidney disease, and death from renal or cardiovascular causes. What had previously been lacking is data regarding the safety and efficacy of initiating SGLT2 inhibitors soon after admission for decompensated heart failure.
Most recently, the SOLOIST-WHF trial4 sought to address that question. This was a randomized controlled trial involving a total of 1,222 patients with heart failure (both reduced and preserved ejection fraction, with an LVEF <50% in 79% of patients in both arms) followed for a median of 9 months. Patients were randomized 1:1 and received sotagliflozin 200 mg daily, titrated to 400 mg daily depending on side effects, or placebo, either before or within 3 days of discharge. The trial was ended early due to loss of funding from the sponsor amid the ongoing COVID-19 pandemic. However, among patients receiving sotagliflozin, there was a significant reduction in the (revised) primary endpoint of cardiovascular death and hospitalizations/urgent visits for heart failure (hazard ratio 0.67; 95% confidence interval, 0.52 to 0.85) that was driven primarily by a reduction in hospitalizations and urgent visits for heart failure (hazard ratio 0.64; 95% confidence interval, 0.49 to 0.83). Prespecified subgroup analysis suggested a similar benefit in the primary endpoint for patients with LVEF <50% and for those with LVEF ≥50%. Though no benefit was seen in death from cardiovascular causes, early closure of the trial limited the statistical power to assess secondary endpoints.
Ivabradine has been shown to reduce heart failure hospitalizations in patients with HFrEF and resting heart rate greater than 70 beats per minute5 after maximizing beta-blocker therapy. This patient has a resting heart rate of 65 beats per minute and is unlikely to benefit from the addition of ivabradine.
There is no evidence in this patient to suggest that increasing frequency of diuretic administration would prevent future heart failure hospitalizations. Bumetanide and metolazone doses should be titrated only to maintain euvolemia. The patient would benefit from close follow-up in the ambulatory heart failure clinic for assessment of volume status and to evaluate for any needed changes in diuretic regimen after initiation of sotagliflozin.
References
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.
Packer M, Anker SD, Butler J,et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020;383:1413-24.
Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436-46.
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 2020;Nov 16:[Epub ahead of print].
Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2017;70:776-803.
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