Dapagliflozin in a Real-World Chronic Heart Failure Population: How Many Are Actually Eligible?

Abstract

<b><i>Background:</i></b> In patients with heart failure (HF) and reduced ejection fraction (HFrEF) with or without type 2 diabetes mellitus, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was recently shown to reduce the risk of worsening HF or death from cardiovascular causes in the dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF) trial. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF enrolment criteria. <b><i>Methods:</i></b> This is a single-center retrospective study enrolling consecutive, unselected patients followed up in an HF clinic from 2013 to 2019. Key DAPA-HF inclusion criteria (i.e., left ventricular ejection fraction [LVEF] ≤40% and NT-proBNP ≥600 pg/mL [or ≥900 pg/mL if atrial fibrillation]) and exclusion criteria (estimated glomerular filtration rate [eGFR] <30 mL/kg/1.73 m<sup>2</sup> and systolic blood pressure [SBP] <95 mm Hg) were considered. <b><i>Results:</i></b> Overall, 479 patients (age 76 ± 13 years; 50.5% male; 78.9% hypertensive; 45.1% with an eGFR <60 mL/min/1.73 m<sup>2</sup>; 36.5% with TD2M; and 33.5% with ischaemic HF) were assessed. The median SBP was 128.5 (112.0–146.0) mm Hg, mean eGFR was 50.8 ± 23.7 mL/min/1.73 m<sup>2</sup>, and median NT-proBNP was 2,183 (IQR 1,010–5,310) pg/mL. Overall, 155 (32.4%) patients had LVEF ≤40%. According to the DAPA-HF trial key criteria, 90 patients (18.8%) would be eligible for dapagliflozin. The remainder would be excluded due to LVEF >40% (67.6%), eGFR <30 mL/min/1.73 m<sup>2</sup> (19.4%), NT-proBNP below the cutoff (16.7%), and/or SBP <95 mm Hg (6.5%). If we center the analysis to those with LVEF ≤40%, 58.1% would be eligible for dapagliflozin. The remainder would be excluded due to an eGFR <30 mL/min/1.73 m<sup>2</sup> (20%), NT-proBNP below the cutoff (16.1%), and/or SBP <95 mm Hg (8.4%). <b><i>Conclusion:</i></b> Roughly half of our real-world HFrEF cohort would be eligible for dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was an eGFR <30 mL/min/1.73 m<sup>2</sup>. However, two-thirds of patients had LVEF >40%. These findings show that dapagliflozin is a promising complementary new drug in the therapeutic armamentarium of most patients with HFrEF, while highlighting the urgent need for disease-modifying drugs in mid-range and preserved LVEF and the need to assess the efficacy and safety of SLGT2i in advanced kidney disease patients. The results of ongoing SGLT2i trials in these LVEF subgroups are eagerly awaited.

Eligibility of Dapagliflozin and Empagliflozin in a Real-World Heart Failure Population

“…A drawback to our approach is less complete and stringent records on HF status. The eligibility rates we have found among HFrEF-patients are lower than have previously been reported, at 52% vs. 58-69% for DAPA-HF [ 15 – 17 ] and 39% vs. 50-53% for EMPEROR-reduced [ 16 , 17 ]. Similarly to Maltês et al and Monzo et al, our patients are significantly older with worse renal function than trial patients.…”

“…Both DAPA-HF and EMPEROR-reduced have a higher eligibility rate than for sacubitril-valsartan according to PARADIGM-HF-criteria [ 13 ] in our population [ 14 ]. The eligibility rates for DAPA-HF and EMPEROR-reduced have been studied at other centers [ 15 – 17 ] in patients that are regularly followed up at a cardiology outpatient clinic. Our cohort includes a broader category of patients, as we have aimed to include all known HF patients in the community.…”

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence

“…In an interesting analysis performed by Maltês et al aimed at evaluating the generalizability of the results of the DAPA-HF trial, it was noted that the limiting factors to widespread use of dapagliflozin remained the lack of literature regarding efficacy in patients with advanced chronic kidney disease (CKD), defined as eGFR <25 mL/min/1.73 m 2 , and LVEF >40%. 34 Thus, the ongoing trials are focused on bridging this gap. In addition to evaluating the role of dapagliflozin in these patients with advanced CKD and HF with preserved ejection fraction (HFpEF), there is also ongoing research focusing on patients with acute decompensated HF.…”

Decompensated heart failure with reduced ejection fraction: overcoming barriers to improve prognosis in the “vulnerable” period after discharge

“…По данным регистра ADHERE, у пациентов, госпитализированных с СН, скорость клубочковой фильтрации (СКФ) <30 мл / мин / 1,73 м 2 наблюдается в 20 % случаев [49], что предполагает ограничение возможностей назначения АМР и иНГТ2 у каждого пятого пациента. В двух небольших одноцентровых исследованиях использование критериев включения в исследование DAPA-HF позволяло назначить дапаглифлозин 22,3 и 58,1 % пациентам с СНнФВ, причем наиболее частым лимитирующим фактором являлось снижение СКФ <30 мл / мин / 1,73 м 2 [50,51]. Расширение показаний к использованию иНГТ2 у пациентов с более выраженным нарушением функции почек (снижением СКФ до 20 мл / мин для эмпаглифлозина и 25 мл / мин для дапаглифлозина с учетом данных о безопасности в исследованиях EMPEROR-Reduced и DAPA-CKD) позволит увеличить охват пациентов с СНнФВ препаратами данного класса.…”