Optimal Prescription of SGLT2 Inhibitors in Hospitalized HFrEF Patients Could Provide Substantial Benefit

Muthiah Vaduganathan, MD

The latest installment in the TRANSLATE-HF program provides insight into the potential impact of in-hospital initiation on post-discharge mortality and readmission among Medicare beneficiaries with heart failure.

A series of analyses examining data from the Get With the Guidelines-Heart Failure (GWTG-HF) registry, the latest data from the TRANSLATE-HF program suggest that, despite being included in contemporary guidelines and demonstrating efficacy in multiple phase 3 clinical trials, early adoption of SGLT2 inhibitors remains low prior to hospitalization and within the immediate post-discharge, which investigators purport represents an addressable gap in care.

“Medicare beneficiaries eligible for dapagliflozin after HF hospitalization, including those well-treated with other therapies, face high risks of mortality and HF readmission,” said Muthiah Vaduganathan, MD, lead investigator and cardiologist at Brigham and Women’s Hospital, in a statement. “If risk reductions in clinical trials can be fully realized, absolute benefits of SGLT-2 inhibitors among eligible candidates are anticipated to be substantial in the high-risk post-discharge setting.”

An industry-education collaboration, TRANSLATE-HF was designed as a series to include 6 studies to identify knowledge gaps and treatment barriers related to SGLT2 inhibitor use in heart failure management. With previous TRANSLATE-HF analyses presented at AHA 2020 and ACC 2021, the program has outlined the optimal patient population for dapagliflozin based on the FDA label and detailed the lack of prescribing among patients with comorbid chronic kidney disease.

The most recent analysis from the program, which was presented at the American Heart Association (AHA) 2021 Scientific Sessions, assessed prescribing data among Medicare Beneficiaries with heart failure with reduced ejection fraction hospitalized in 2016 at a hospital in the GWTG-HF Registry with linked claims data for a least 1 year following discharge. The primary aim of the analysis was to identify patients considered eligible for an SGLT2 inhibitor prescription under the FDA label for dapagliflozin overall and among multiple subgroups defined by age, sex, race, location, eGFR, diabetes status, and presence of triple therapy.

Investigators identified a cohort of 7767 patients hospitalized for HFrEF. Of these, 6218 would have been considered eligible for an SGLT2 inhibitor prescription. This cohort of eligible patients had a mean age of 79±8 years, 38% were women, 12% were Black. Investigators pointed out an assessment of prescription data from these patients indicated use of beta-blockers, ACE inhibitors or ARBs, MRA, ARNI, and triple therapy was recorded in 88%, 64%, 29%, 3%, and 20%, respectively.

Among patients considered eligible for dapagliflozin, the 10-year incidence of mortality was 37% (95% CI, 36-38) and the rate of heart failure readmission was 33% (95% CI, 32-34). Additionally, investigators pointed out the 1-year incidence of mortality and rate of heart failure readmission exceed 25% in all subgroups. In an analysis of patients already on triple therapy, the 1-year incidence of mortality was 26% (95% CI, 24-29) and the rate of readmission was 30% (95% CI, 27-32).

After application of relative risk reductions observed in the DAPA-HF trial, estimated absolute risk reductions with optimal implementation of dapagliflozin were projected to be 5% (95% CI, 1-9) for 1-year incidence of mortality and 9% (95% CI, 5-12) for rate of heart failure readmission. When assessing the projected number needed to treat (NNT) to prevent a single death at 1 year was 19 (11-114) and the NNT to prevent a single heart failure readmission was 12 (8-21).

Investigators cautioned clinicians to consider limitations within their analysis when interpreting results. These included being restricted to Medicare Fee-for-Service beneficiaries, being restricted to hospitalizations occurring within 2016, and reliance on the DAPA-HF effect sizes.

This study, "Projected Clinical Benefits of Implementation of SGLT-2 Inhibitors among Medicare Beneficiaries Hospitalized for Heart Failure,” was presented at AHA 2021 and simultaneously published in the Journal of Cardiac Failure.