Key Subgroups of HF Patients Missing Out on SGLT2 Inhibitors: Registry Data

Prescribing of sodium-glucose cotransporter 2 (SGLT2) inhibitors for ambulatory patients with heart failure (HF) has increased significantly in recent years. However, several subgroups, including women, older patients, and those with high blood pressure burden, are lagging behind in their receipt of the medications, according to data from a US-based outpatient registry.

SGLT2 inhibitors were rapidly incorporated into HF clinical practice guidelines in the United States and Europe based on data from the EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER trials, among others, supporting their benefits in reducing adverse clinical outcomes and hospitalizations in patients with HF across the spectrum of ejection fraction.

The registry data, published recently in JAMA Cardiology, show that between 2019 and 2023, rates of SGLT2 inhibitor prescribing in all HF patients increased from 4.6% to 16.2% (P < 0.01). During the same time period, patients with HF with reduced ejection fraction (HFrEF) saw an increase from 5.1% to 28.5%, while those with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) saw an increase from 4.5% to 12.8% (P < 0.01 for both comparisons).

These trends have emerged within just 3 years of the US Food and Drug Administration’s  approval of dapagliflozin (Farxiga; AstraZeneca) for HFrEF and within 1 year of the approval of empagliflozin (Jardiance; Boehringer Ingelheim/Eli Lilly) for HFpEF.

Speaking with TCTMD, lead author Abdelghani El Rafei, MD (University of Colorado Anschutz Medical Campus, Aurora, CO), said the uptake of SGLT2 inhibitors in real-world practice appears to have happened a bit more rapidly than prior trends would have suggested.

“Data on [angiotensin receptor-neprilysin inhibitors], for example, show an uptake of about 30% at 3 years after FDA approval,” he added. “I think the takeaway is that the data from the [SGLT2 inhibitor] trials have been convincing, the medications are easy to use, they don’t require uptitration, and there’s very little monitoring that you need to do with these agents. Those factors contribute to the appeal of them in practice, along with the well-documented benefits.”

Another thing that has likely eased the arrival of SGLT2 medications into HF practice is that they began as diabetes therapies, “so that’s definitely part of the reason for the uptake that we saw,” El Rafei added.

Practice Varies Considerably

The investigators analyzed data from 759,915 patients (mean age 70 years; 47% women) who had a diagnosis of HF and were enrolled in the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry, which tracks quality improvement in ambulatory cardiovascular care.

Over the study period, approximately 10% of the population was prescribed an SGLT2 inhibitor. Compared with those who did not receive a prescription, those who did were younger and more likely to have hypertension and diabetes.

An analysis of factors associated with a decreased likelihood of SGLT2 inhibitor prescribing identified female sex (adjusted OR 0.79, 95% CI 0.77-0.81), higher systolic blood pressure (adjusted OR 0.78; 95% CI 0.77-0.79), and older age (adjusted OR 0.76; 95%CI 0.75-0.77).

The registry data also indicate a high degree of practice-level variation in prescribing among the 191 US sites included, ranging from a low of 2% to a high of 60%, with a median of 15%. Practice variation by EF ranged from 4% to 60% in those with HFrEF and from 3% to 42% in those with HFmrEF or HFpEF. Even after adjustment for patient- and practice-level characteristics, the variation remained.

“I think what this tells us is that there are processes at the higher-use sites that can be emulated at the sites that are not at the same use rate for SGLT2s,” El Rafei said. These could include implementation of reminders in electronic health records and other quality-improvement measures focused on optimizing HF therapies.

“There’s also work that can be done on a policy level to try to help increase the uptake of these medications,” he added. “It could be including SGLT2 inhibitors as a core metric for fee-for-service, improving the copay for these medications, or better negotiation from the government side to reduce the prices of these medications.”

As TCTMD has previously reported, lowering the costs of the drugs could shift them into the high-value category and increase their uptake.

El Rafei and colleagues say the findings put an emphasis on the need to improve uptake in women and older patients, two groups that also have been shown to be less likely to receive the drugs when hospitalized for HF, irrespective of their ejection fraction. Similarly, the low use in patients with high blood pressure should be a wake-up call given their well-documented blood pressure-lowering effects.

To TCTMD, El Rafei said in some cases more physician education may be needed on who should be considered for SGLT2 therapy, as a way to ensure that those with a high likelihood of benefit are receiving it in a timely manner before adverse events and hospitalizations occur.

“Providers should not be afraid to prescribe given the magnitude of clinical benefit that these medications have for patients with heart failure,” he added. “We hope these data can . . . raise awareness that there are subgroups that are still experiencing underuse compared to others.”