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Therapeutic approaches in heart failure with diabetes

Presented by
Prof. Lynne Stevenson, Vanderbilt University Medical Center, USA
AHA 2021
The new therapeutic options for patients with heart failure (HF) offer physicians a growing number of choices in finding the right integrated approach in the treatment of HF patients with diabetes mellitus. Key considerations, according to Prof. Lynne Stevenson (Vanderbilt University Medical Center, TN, USA) are the robustness or frailty of the patient, the stage of disease, and the patient’s financial resources and accessibility to healthcare facilities [1].

The 3 fundamental therapies for patients with HF with reduced ejection fraction (HFrEF) are angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and β-blockers. The first choice of therapy depends on heart rate, blood pressure, and renal function. “For example, in patients with an increased heart rate, β-blockers would be the first therapy of choice. If we want to expand from our fundamental therapies, angiotensin receptor-neprilysin inhibitor (ARNIs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors are the available options. Although ARNIs provide a clear additional benefit for our patients, we have to consider blood pressure and tolerance of ACE inhibitors or ARBs.” An analysis of the PARADIGM-HF trial (NCT01035255) showed that patients on the ARNI sacubitril/valsartan with a baseline systolic blood pressure ≤110 mmHg experienced hypotensive events in 25% of the cases [2]. “Therefore, patients with a blood pressure <100 mmHg, in general, do not qualify for this expansion option.” On the other hand, SGLT2 inhibitors do not display much blood pressure lowering [3]. In addition, SGLT2 inhibitors may have an added benefit for renal function. Since half of the patients with HF have chronic kidney disease and the mortality in patients with HF increases when renal function drops (RR of 1.4 when eGFR <60), this is an important factor to consider [4,5]. “In summary, SGLT2 inhibitors might be favoured over ARNIs in less robust patients with HFrEF.”

“In patients with a preserved EF (HFpEF), there is no recommended routine neurohormonal therapy,” Prof. Stevenson continued. “Controversial indications for ARBs and MRAs, β-blockers for arrhythmias or ischaemia, and perhaps SGLT2 inhibitors for renal preservation are the options we currently have. In addition, although SGLT2 inhibitors show benefits in patients with HFpEF, the benefits may be limited to the lower EFs within this population [6].”

“Importantly, we need to tackle obesity as a cause and aggravator of the disease. The prevalence of obesity is >30% in most [US] states. If we do not address this problem, the treatment effect of emerging therapies will remain limited. Semaglutide, a GLP-1 antagonist, showed a remarkable 18% weight reduction in overweight or obese adults in 2 recent studies. However, the tolerance of this agent is problematic in many patients [7,8].

In conclusion, therapy design in patients with HF and diabetes is challenging. The robustness, disease stage, and resources of the patients are important decision criteria, and the therapy effectiveness will remain limited in this population if obesity is not adequately addressed.


    1. Stevenson LW. An Abundance of Therapeutics: An Integrated Approach to Managing HF with DM. PR.ME.461, AHA 2021 Scientific Sessions, 13–15 November.

    2. Böhm M, et al. Eur Heart J. 2017;38(15):1132–1143.

    3. Böhm M, et al. J Am Coll Cardiol. 2021;78(13):1337–1348.

    4. Dries DL, et al. J Am Coll Cardiol. 2000;35(3):681–689.

    5. McGuire DK, et al. J Am Coll Cardiol. 2021;6(2):148–158.

    6. Packer M, et al. Circulation. 2021;144:1193–1195.

    7. Wilding JHP, et al. N Engl J Med 2021;384:989–1002.

    8. Rubino D, et al. J Am Coll Cardiol. 2021;325(14):1414–1425.


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