Best Practices for Starting SGLT2 Inhibitors in HFpEF Treatment

Drs Matthew Konerman and Sarah Adie share expert insights on SGLT2 inhibitor use in managing heart failure with preserved ejection fraction.
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Matthew C. Konerman, MD: Hello. I'm Dr Matthew Konerman. I'm a heart failure specialist at the University of Michigan Health. I'm here today to discuss sodium glucose cotransporter 2 (SGLT2) inhibitors in the treatment of heart failure with preserved ejection fraction (HFpEF) with my dear friend, Sarah Adie, PharmD, from the University of Michigan.
Sarah K. Adie, PharmD: Hi, Matt. It's great to be here.
Konerman: It's great to have you. Let's get started. We are here to discuss a very hot topic in cardiology: SGLT2 inhibitors in HFpEF. We have known that SGLT2 inhibitors have a role in the treatment of heart failure, particularly heart failure with reduced ejection fraction, as demonstrated in the DAPA-HF and EMPEROR-Reduced trials.
Today we are going to focus on a review of evidence supporting the use of SGLT2 inhibitors in HFpEF. We will also then transition to discussing common questions regarding the clinical use of SGLT2 inhibitors in HFpEF. We know that SGLT2 inhibitors are beneficial in HFpEF based on two large, randomized trials that were published recently.
In the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction (DELIVER) trial, over 6000 patients with heart failure and an ejection fraction greater than 40% were randomized to receive dapagliflozin vs placebo and followed for a median of 2.3 years. Less than half of the patients had type 2 diabetes.
The composite endpoint of worsening heart failure or cardiovascular death was significantly reduced to 16.4% in the dapagliflozin arm compared with 19.5% in the placebo arm. This difference was driven by differences in worsening heart failure.
The second trial was the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction, the EMPEROR-Preserved trial. This study had very similar results. In almost 6000 patients with heart failure and an ejection fraction greater than 40%, patients were randomized to empagliflozin or placebo and followed for about 2.2 years.
Again, SGLT2 inhibition with empagliflozin was associated with a significant reduction in the composite primary endpoint of cardiovascular death and heart failure hospitalization. The benefit was driven by a reduction in heart failure hospitalizations. Interestingly, there was no significant difference in total hospitalizations between the two groups, which does raise the importance of managing other comorbid conditions in HFpEF, given the rates of non-cardiovascular hospitalizations in that type of heart failure.
Given the supportive data from these two trials, the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure supports the use of SGLT2 inhibitors in HFpEF with a class 2a recommendation. Similarly, the recent 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction also gives a class 2a recommendation, supporting SGLT2 inhibitor use.
We know the evidence, now, that led SGLT2 inhibitors to be indicated in the treatment of HFpEF
Sarah, what should be considered when starting an SGLT2 inhibitor? What dose do you use? What contraindications should you consider?
Adie: Good questions, Matt. In terms of patient selection, we know that SGLT2 inhibitors can be used in the treatment of patients with HFpEF, with or without type 2 diabetes. These agents are contraindicated, however, in patients with type 1 diabetes or if they have prior diabetic ketoacidosis.
A dose of 10 mg daily for both dapagliflozin and empagliflozin has been approved for the heart failure indication. Notably, there are differences in terms of estimated glomerular filtration rates (eGFR) cutoff for both agents compared with the FDA indication for patients with type 2 diabetes, as the heart failure trials actually included patients with an eGFR down to 20 mL/min/1.73 m2 for empagliflozin and 25 mL/min/1.73 m2 for dapagliflozin.
Thinking about the impact on other guideline-directed medical therapy, SGLT2 inhibitors may affect potassium excretion. In a meta-analysis of clinical trials evaluating SGLT2 inhibitor treatment in those with heart failure, their use was shown to be associated with reduced discontinuation of mineralocorticoid receptor antagonist therapy.
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