SGLT2i Still Underprescribed in HFrEF, New US Analysis Confirms

Only one in five patients hospitalized for heart failure with reduced ejection fraction (HFrEF) receive a prescription for an SGLT2 inhibitor at discharge, according to a contemporary US analysis.

Among hospitals participating in the American Heart Association Get With The Guidelines–Heart Failure (GWTG-HF) registry, 74.6% of all sites discharged fewer than 25% of patients with prescriptions for SGLT2 inhibitors. Additionally, fewer than 10% of all individuals in the study received prescriptions for the quadruple combination of SGLT2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and an ARB or angiotensin receptor–neprilysin inhibitor (ARNI) as recommended in the most recent US And European guidelines.

"The good news is that the rate of SGLT2 inhibitor prescription at discharge was increasing over the 12-month study period, but use of SGLT2 inhibitors at discharge was still less than 30% among eligible patients during the latest months of our study from April to June 2022," senior study author Stephen J. Greene, MD (Duke Clinical Research Institute, Durham, NC), said in an email.

Greene presented the data at last month's European Society of Cardiology Heart Failure 2023 Congress. The study, with Greene as senior author and Jacob B. Pierce, MD, MPH (Duke University School of Medicine, Durham, NC), as first author, was published simultaneously in JAMA Cardiology.

Prescription Shortfalls

Pierce et al examined data on 49,399 patients (median age 67 years; 33.5% female) hospitalized for HFrEF between July 2021 and July 2022 at 489 registry hospitals.

Compared with those who did not receive a "gliflozin" prescription, those who did were more often younger, Black, diabetic, had private insurance or Medicaid, and had both diabetes and chronic kidney disease (CKD). Patients with lower ejection fraction, higher body mass index, or an implantable cardioverter-defibrillator also had higher rates of SGLT2 prescribing.

Having kidney insufficiency or anemia, or being a current smoker, were linked to lower likelihood of getting an SGLT2 inhibitor.

The next step is closing these gaps in quality of care and doing so with a sense of urgency. Stephen J. Greene

Among patients who received a gliflozin prescription, use of background triple therapy was higher than in those who did not (46.3% vs 27.6%; P < 0.001). Looking at the 461 individual hospitals with 10 or more eligible discharges, only 4% discharged half or more patients with a SGLT2 inhibitor prescription.

Hospital-level factors associated with not receiving a prescription at discharge included having fewer beds, a lack of interventional cardiac catheterization and heart transplantation services, being a nonteaching center, and being located in the western United States or in a rural area. However, in multivariable analyses, only the number of beds remained a predictor (OR 1.12; 95% CI 1.07-1.16).

Urgent Need to Close Care Gaps

Despite the low prescribing rates of SGLT2 inhibitors, the authors note that an overall rate of 20% in this contemporary cohort is actually not unique and represents higher uptake than might be expected for a new, evidence-based therapy. An analysis of the GWTG-HF registry following approval of ARNI for HFrEF in 2015, for example, found that only a little over 2% of hospitalized patients were receiving ARNI prescriptions at discharge.

Still, they say it "remains concerning that the vast majority of patients expected to derive benefit are not receiving this medication."

To TCTMD, Greene said many of the patient characteristics associated with discharge prescription for SGLT2 inhibitors were "unfortunate" but not surprising.

"Eligible females were less likely than eligible males to be prescribed an SGLT2i, showing a sex-based disparity," he noted. "Likewise, many of the relationships were consistent with the risk-treatment paradox we often see with heart failure therapies, where the patients at greatest risk and in greatest clinical need are less likely to receive appropriate therapy."

Although high drug costs remain a barrier, with a recent analysis suggesting that some Medicare patients end up paying over US $900 per year out of pocket for their SGLT2 inhibitor alone, Greene said the current study, looking specifically at prescribing patterns, adds to others suggesting out-of-pocket costs are not the dominant explanation for the widespread underuse of both branded and generic guideline-directed medical therapies, or for the magnitude of the prescribing gaps.

"We saw enormous hospital-level variation in discharge use of SGLT2i, with some hospitals discharging 100% of eligible patients on an SGLT2 inhibitor while others [were] discharging zero patients on an SGLT2 inhibitor. This variation persisted even after adjusting for characteristics of the patient population at those hospitals, including insurance status, and other hospital characteristics," he added. "In aggregate, these data strongly suggest a quality-of-care issue driving such large differences across US hospitals. I view this paper as really defining the scope of the problem. The next step is closing these gaps in quality of care and doing so with a sense of urgency."

L.A. McKeown is a Senior Medical Journalist for TCTMD, the Section Editor of CV Team Forum, and Senior Medical…

Pierce JB, Vaduganathan M, Fonarow GC, et al. Contemporary use of sodium-glucose cotransporter-2 inhibitor therapy among patients hospitalized for heart failure with reduced ejection fraction in the US: The Get With The Guidelines–Heart Failure registry. JAMA Cardiol. 2023;Epub ahead of print.

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