Lessons from SGLT-2 inhibitors: rethinking endpoints for heart failure studies

ARTICLE: Lessons from SGLT-2 inhibitors: rethinking endpoints for heart failure studies

AUTHORS: Sheng Fu, Sheldon E Litwin, Ryan J Tedford

JOURNAL: Nat Med. 2021 Nov 11. doi: 10.1038/s41591-021-01565-6. Online ahead of print.

SGLT-2 inhibitors show promise for treatment of heart failure with preserved ejection fraction, but clinical data are nuanced. Appropriate endpoint selection will be key to deciphering their benefits.

When treating heart failure with reduced ejection fraction (HFrEF), patients and providers are fortunate to have numerous evidence-based therapies that prolong life available; the serendipitous discovery that sodium-glucose transporter 2 (SGLT-2) inhibitors could reduce heart failure events has added to the already rich armamentarium of therapies available in this setting1,2. However, when it comes to heart failure with preserved ejection fraction (HFpEF), clinical trials have had limited success. Recently, the EMPEROR-Preserved study (n = 5,988) reported a reduction in the composite endpoint of cardiovascular death or heart failure hospitalization with the SGLT-2 inhibitor empagliflozin3, making this arguably the first large HFpEF trial to reach its primary endpoint. However, the outcome was driven solely by a reduction in heart failure hospitalizations with no difference in total or cardiovascular mortality, no change in quality of life and minimal change in natriuretic peptide levels, highlighting the ongoing challenges around endpoint selection for clinical trials for new agents in patients with HFpEF (Fig. 1).

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