A 61-year-old man who has been seeing you in clinic for the last 3 years for relatively stable heart failure with reduced ejection fraction (HFrEF) presents for a planned follow up with a repeat echo. You saw him approximately 6 months ago and uptitrated his furosemide in view of some paroxysmal nocturnal dyspnea.
Background history includes the following:
HFrEF:
ICD inserted 4 years ago (primary prevention)
Echocardiogram (1 month ago): left ventricular ejection fraction (LVEF) 32%, unchanged. Mild mitral regurgitation, normal right ventricular function.
Coronary artery disease:
Myocardial infarction i 2012: Percutaneous coronary intervention to left anterior descending artery, mild diffuse disease elsewhere.
Type 2 diabetes mellitus
Hypertension
Current medications are:
Metformin 1g once daily
Sacubitril/valsartan 97/103mg
Bisoprolol 10mg once daily
Spironolactone 25mg once daily
Atorvastatin 80mg once daily
Aspirin 81 mg once daily
Furosemide 40mg twice daily
Labs and investigations performed over the last 3 months demonstrate:
His blood pressure today is 115/80 mm Hg, and his heart rate (HR) is 60 beats per minute. He has pedal edema bilaterally at the ankles but otherwise appears euvolemic. He continues to have NYHA II symptoms.
What is the next most important change in his cardiovascular management to improve his overall outlook?
Show Answer
The correct answer is: D. Add dapagliflozin 10mg once daily.
The addition of dapagliflozin confers a reduction in the risk of future atherosclerotic events. Furthermore, the recent FDA label for dapagliflozin in HFrEF reflects its emerging role as the 4th pillar of heart failure therapy alongside renin-angiotensin system inhibitors, beta blockers and mineralocorticoid receptor antagonists.
The addition of an SGLT-2 inhibitor is the most important evidence-based change to this patient's cardiovascular management. The prescription of any SGLT-2 inhibitor will reduce the risk for future atherosclerotic events in this patient by approximately 10-15% given his established coronary artery disease.1 More recently, patients such as fthiswith HFrEF were included in the DAPA-HF2 and EMPEROR-reduced3 clinical trials. In those trials, patients receiving either dapagliflozin or empagliflozin respectively experienced a 25% reduction in the risk of cardiovascular death or heart failure hospitalization/ER visit over a 1.5 year period of follow up, regardless of whether they had diabetes. This patient is also likely to derive kidney protection when treated with dapagliflozin,2 empagliflozin3 or canagliflozin,4 given his underlying kidney dysfunction.
Ivabradine has been shown to reduce symptoms and HF hospitalizations in patients with HFrEF whose HR remains elevated (>70bpm) despite maximal beta blocker use.5 In this context, the patient is unlikely to benefit significantly from ivabradine as he appears well beta blocked with a resting HR of 60bpm.
While the addition of a GLP-1 receptor agonist with proven CV benefit (semaglutide,6 dulaglutide,7 liraglutide8) will reduce the patient's risk of future atherosclerotic events, exenatide does not have a label for cardiovascular benefit.9 Given the expected benefit on HFrEF and eGFR, the SGLT-2 inhibitor would be the agent of choice.
Cardiac resynchronization is unlikely to be of significant benefit to this patient as his ECG does not show evidence of a dyssychrony (normal QRS duration).10
Educational grant support provided by: Boehringer Ingelheim Lilly.
To visit the hub for the CV Risk in Diabetes: Emerging Science Grant, click here!
References
Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis [published online ahead of print, 2020 Oct 7]. JAMA Cardiol. 2020;e204511.
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.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019;380:2295-306.
Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376:875-85.
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016;375:1834-44.
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019;394:121-30.
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016;375:311-22.
Holman RR, Bethel MA, Mentz RJ, et al. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2017;377:1228-39.
Francis GS, Greenberg BH, Hsu DT, et al. ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant. J Am Coll Cardiol 2010;56:424-53.
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