https://orcid.org/0000-0002-0185-7511
Research letter
Patients with heart failure (HF) represent a vulnerable population in need of optimal treatment and in-depth clinical care. In recent years, numerous randomized controlled trials have evaluated the efficacy of sodium–glucose cotransporter 2 inhibitors (SGLT2i) and demonstrated decreased hospitalization rates for HF and a better cardiorenal outcome in diverse HF populations comprising HF patients with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction.1 Although SGLT2i were primarily developed as antidiabetic agents, their profound reduction in cardiovascular (CV) risk cannot solely be explained by a metabolic rearrangement and normalization of haemoglobinA1c (HbA1c) levels, and thus HF patients seem to benefit from SGLT2i treatment regardless of their diabetes status.
Since the beneficial effects of SGLT2i in HF patients are well known, real-world data on the clinical implementation of these agents following the availability of CV outcome trial data seems of utmost importance. Therefore, we aimed to elucidate prescription trends of SGLT2i over the past 6 years.
We identified patients presenting with HF who were hospitalized at the Vienna General Hospital, a university-affiliated tertiary care centre, between January 2017 and October 2022. All prescriptions of SGLT2i (dapagliflozin and empagliflozin)—including marketed fixed-dose combinations with other glucose-lowering drugs—were identified from discharge summaries. HF was defined in accordance with the current guidelines (2021) of the European Society of Cardiology (ESC).2 All statistical analyses were performed using R (version 4.0.4; Vienna, Austria).
In total, 2673 patients with HF were included in the present analyses. The patients’ median age was 75 years [interquartile range (IQR) 64–83 years], and 1067 (39.9%) patients were female. Among the 2673 patients with signs and symptoms suggestive of HF, 1086 (40.6%) had a documented left ventricular ejection fraction (LVEF) ≤40% (HFrEF), 445 (16.6%) had a LVEF between 40 and 50% (HFmrEF), and 1142 (42.7%) had a LVEF > 50% (HFpEF). In the overall cohort, 382 (14.3%) patients received an SGLT2i, with 213 (19.6%) patients in the HFrEF group, 69 (15.5%) patients in the HFmrEF group, and 100 (8.8%) patients in the HFpEF group, respectively. Empagliflozin (58.7%) was more often used than dapagliflozin (41.3%).
While patients receiving SGLT2i presented more frequently with coronary artery disease (53.7 vs. 39.6%; P-value < 0.001), the rate of chronic kidney disease (CKD) did not significantly differ between both groups (SGLT2i: 15.5% vs. no SGLT2i: 18.1%; P-value = 0.221).
Patients on SGLT2i more often received other HF drugs such as sacubitril/valsartan (27.7 vs. 5.5%; P-value < 0.001), beta-blockers (83.5 vs. 62.1%; P-value < 0.001), and/or mineralocorticoid receptor
antagonists (MRA, 73.0 vs. 43.3%; P-value < 0.001). Interestingly, the co-prescription of renin-angiotensin system acting agents did not differ between groups (SGLT2i: 56.5% vs. no SGLT2i: 55.6%; P-value = 0.773). In sensitivity analyses for specific time frames (Supplementary material online, Table S1) and in patients with reduced EF, these results remained similar.
As shown in Figure 1, the prescription of SGLT2i significantly increased from the beginning to the end of the inclusion period. In detail, it climbed from 6.8% in 2017 to 56.6% in 2022 in the HFrEF group (P-trend < 0.001), from 3.3 to 49.2% in the HFmrEF group (P-trend < 0.001), and from 1.9% to a still very low 26.4% in the HFpEF group (P-trend < 0.001). While the prescription of SGLT2i in HFrEF patients started to increase after the presentation of the DAPA-HF trial,3 the SGLT2i prescription in HFmrEF and HFpEF patients showed a marked rise after the presentation of the new HF ESC guidelines (2021) (before ESC guideline presentation: 5.3 vs. 32.2% after ESC guideline presentation, P-value < 0.001) and the EMPEROR-Preserved trial.2,4
Prescription trend of SGLT2i over the past 6 years. EMPEROR Pres., EMPEROR Preserved; EMPEROR Red., EMPEROR Reduced; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction.
In summary, we assessed the status of clinical implementation of SGLT2i in 2673 individuals with HFpEF, HFmrEF, and HFrEF. Despite a steep upward trend in prescriptions of SGLT2i over the past 6 years, they are still underutilized in daily clinical practice, especially in patients with HFpEF. Fortunately, prescription practices changed after the presentation of the SGLT2i HF outcome trials and the corresponding adaptations of ESC guidelines (for HFrEF). The influence of the recently published DELIVER trial5 and of ongoing SGLT2i outcome trials on prescribing patterns remains to be seen and has to be evaluated in future studies.
SGLT2i was frequently prescribed in combination with other HF therapies such as sacubitril/valsartan, beta-blockers, and MRA. Thus, the utilization of other HF therapies was more common in patients treated with SGLT2i than in those without SGLT2i, which might be due to a higher incidence of HFrEF patients in the SGLT2i group. However, we also observed similar results in a subgroup analysis including HFrEF patients, which could reflect a prescribing pattern aiming to combine modern HF therapies. The use of SGLT2i in patients with HFpEF still needs to be expanded, as current treatment options are limited in this vulnerable patient population. In contrast to previous observation, CKD no longer appears to be an impediment for the prescription of SGLT2i in the present cohort.6
Patients were included in a single tertiary academic site, and therefore, results might not be generalizable to the entire health care system. Furthermore, we were not able to assess adherence rates.
To conclude, the prescription of SGLT2i is constantly rising due to greater awareness among cardiologists and other specialists in internal medicine. Nevertheless, despite a growing evidence on the reduction of CV events by SGLT2i, our data show that there is still room for improvement in prescribing of these cardioprotective agents, especially in patients with HFpEF. Increasing utilization of SGLT2i could provide an additional opportunity to improve CV health in this high-risk patient population.
Acknowledgement
None.
Funding
None.
Conflict of interest: none declared.
Ethics
The study protocol complied with the declaration of Helsinki and was approved by the local ethics committee of the Medical University of Vienna EK (2267/2019).
Data availability
Data available on request.
