SGLT2i improves health status in HFmrEF/HFpEF

Introduction and methods

Background

As patients with HFmrEF or HFpEF experience a high burden of symptoms and physical limitations, and a poor quality of life [1], improving their health status is a crucial goal of patient management. Although several RCTs have shown that SGLT2i treatment can improve health status in this patient population [2-5], there is still uncertainty about the magnitude and consistency of the effects of SGLT2is on health status, especially in HF patients with truly normal LVEF.

Previously, the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial showed that dapagliflozin reduced the risk of CV death or worsening HF events [6]. To examine the effects of dapagliflozin treatment on health status, the authors conducted a prespecified analysis of this trial.

Aim of the study

The study aims were: (1) to evaluate whether the effects of dapagliflozin on clinical outcomes in the DELIVER trial varied according to the degree of symptomatic impairment at baseline; and (2) to examine the effects of dapagliflozin on the broad range of health status outcomes as measured by the various domains of the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Methods

In the international, prospective, randomized, double-blind, placebo-controlled DELIVER trial, 6263 patients with symptomatic HFmrEF/HFpEF (NYHA class II–IV HF symptoms, LVEF >40%, elevated NT-proBNP levels) were randomized to dapagliflozin 10 mg or placebo, stratified by T2DM status. For the current analysis, data from 5795 patients with available KCCQ data at baseline were collected. At 1, 4, and 8 months, scores on the following KCCQ domains were evaluated: Total Symptom Score (TSS), Physical Limitations Score (PLS), Clinical Summary Score (CSS), and Overall Summary Score (OSS).

Outcomes

In the DELIVER trial, the primary endpoint was a composite outcome of CV death or worsening HF event (defined as unplanned HF hospitalization or urgent HF visit requiring intravenous therapy). A (prespecified) key secondary endpoint in this trial was the change in KCCQ-TSS from baseline to 8 months.

Main results

Clinical outcomes

• Patients in the lowest tertile of KCCQ-TSS at baseline (<63 points; n=2040) showed a higher rate of CV death or worsening HF events compared with patients in the middle tertile (63–84 points; n=1955) and those in the highest tertile (>84 points; n=1800): 7.8, 5.6, and 4.8 per 100 patient-years, respectively (P<0.001).
• The effect of dapagliflozin versus placebo on reducing this primary endpoint appeared to be more pronounced in the group with the lowest tertile of baseline KCCQ-TSS (HR: 0.70; 95%CI: 0.58–0.84; P<0.001) compared with the middle tertile (HR: 0.81; 95%CI: 0.65–1.01; P=0.06) and highest tertile groups (HR: 1.07; 95%CI: 0.83–1.37; P=0.62) (P for interaction=0.026).
• When the KCCQ-TSS at baseline was examined as a continuous variable, there was a graded relationship between a lower baseline KCCQ-TSS and greater reduction in the primary endpoint with dapagliflozin versus placebo (P=0.008).

Health status outcomes

• Compared with placebo treatment, patients treated with dapagliflozin showed an improvement from baseline to 8 months in mean KCCQ-TSS (+2.4 points; 95%CI: 1.5–3.4 ), mean KCCQ-PLS (+1.9; 95%CI: 0.9–3.0), mean KCCQ-CSS (+2.3; 95%CI: 1.5–3.2), and mean KCCQ-OSS (+2.1; 95%CI: 1.3–2.9) (P<0.001 for all comparisons). These improvements could already be observed at 1 month and became more pronounced over time.
• Responder analyses showed that fewer patients in the dapagliflozin group had a clinically meaningful deterioration (i.e., ≥5-point decline) in the KCCQ-TSS compared with the placebo group (21% vs. 26%; OR: 0.76; 95%CI: 0.66–0.88; number needed to treat (NNT): 20).
• In addition, more patients in the dapagliflozin group had at least a small improvement in the KCCQ-TSS (i.e., ≥5 points; OR: 1.16; 95%CI: 1.03–1.30; NNT: 28) or at least a moderate improvement (≥10 points; OR: 1.15; 95%CI: 1.02–1.30; NNT: 29) compared with the placebo group. However, there was no difference between the groups in the proportion of patients achieving at least a large improvement (≥15 points) in the KCCQ-TSS at 8 months (OR: 1.12; 95%CI: 0.99–1.28; NNT: 42).
• Broadly similar results were seen for differences between the dapagliflozin and placebo groups in change in the KCCQ-PLS, KCCQ-CSS, and KCCQ-OSS.
• The treatment effects of dapagliflozin versus placebo on the KCCQ-TSS at 8 months were generally consistent across key demographic and clinical subgroups, including LVEF categories (≤49%, 50%–59%, and ≥60%; P for interaction=0.85), except for subgroups based on NYHA class HF symptoms (P for interaction=0.011) and T2DM status (P for interaction=0.014). When LVEF was analyzed as a continuous variable, there was also no significant interaction (P=0.16).

Conclusion

References

Find this article online at J Am Coll Cardiol.