Background

The implementation of guideline-directed medical therapies (GDMT) for heart failure (HF) into daily medical practice still faces major barriers – despite remarkable evidence-based advances in HF treatment over the last decade. The current ESC and ACC/AHA guidelines recommend both sacubitril/valsartan (S/V) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as first-line therapies for HF with reduced ejection fraction (HFrEF), while the 2021 update of the National Guideline (NVL) Chronic Heart Failure recommends both as therapy escalation.

Methods

Covering 9 quarters (Q), ie the period between January 2020 and March 2022, we investigated the diffusion of novel GDMT into real-world HF care in Germany. Analyses were based upon the IQVIA™ LRx database that contains ~80% of the statutory health insurance claims. Data were extrapolated to total national retail pharmacy sales. We focused on HFrEF using prescriptions of S/V as a proxy.

Results

The number of S/V treated patients increased steeply, from 166,000 in Q1/2020 to 271,000 in Q1/2022, accompanied by a marked surge in the number of patients concomitantly treated with SGLT2i. Thus, the share of combined therapy rose from 6.6% to 30.7% (Figure 1). The proportion of women on S/V remained unchanged at ~31%, which is consistent with the prevalence of women with HFrEF. However, female patients were under-represented in the group jointly treated by S/V and SGLT2i: 18.7% in Q1/2020, 25.1% in Q1/2022. A similar observation was made for older patients (>80 years), irrespective of sex.

With respect to therapy sequence within the jointly treated group, the proportion of patients with simultaneous initiation of S/V and SGLT2i almost doubled (from 20.2% to 37.6%) corresponding to a 14-fold increase in absolute numbers. There, female patients were similarly likely to have started S/V and SGLT2i simultaneously (22.7% in Q1/2020, 42.7% in Q1/2022). The same was true for patients aged >80 years (24.9% in Q1/2020, 43.8% in Q1/2022), irrespective of sex.

The number of new S/V patients increased over time, apparently driven by the simultaneous initiation of S/V and SGLT2i that increased its share from 3.6% in Q1/2020 to 35.7% in Q1/2022 (Figure 2). Again, the increase in absolute numbers was more than 14-fold, from less than 1,000 to almost 14,000 patients per Q (Figure 2).

Conclusion

The number of S/V treated patients as well as the proportion of S/V patients with concomitant SGLT2i steeply increased in the studied period, particularly since mid-2021, ie when the ESC HF guidelines were released. Women and patients at high age remain disadvantaged regarding uptake of GDMT, although the combination therapy of S/V with SGLT2i is similarly frequently installed compared to men.

Hence, use of novel HFrEF GDMT in real-world clinical practice is feasible. Further efforts are needed to fully implement the guideline recommended quick initial administration of quadruple therapy, including both S/V and SGLT2i, into routine HF care in Germany.

Figure 1. Absolute number of patients on S/V treatment with (dark columns) and without (grey columns) concomitant SGLT2i treatment, proportion of combined therapy (blue line), from Q1/2020 to Q1/2022, in Germany.

Figure 2. Composition of new patients on S/V treatment (shaded areas) and number of simultaneous initiations of S/V + SGLT2i (blue columns), from Q1/2020 to Q1/2022, in Germany.

S/V = sacubitril/valsartan; SGLT2i = sodium-glucose cotransporter-2 inhibitors