SGLT2 inhibitor ertugliflozin shows similar mortality but fewer HF hospitalisations

In the VERTIS CV trial, SGLT2 inhibitor ertugliflozin did not meet the primary endpoint but did reduce the risk for first heart failure (HF) hospitalisations compared with placebo in patients with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) with or without a history of HF [1]. These findings are consistent with results for other SGLT2 inhibitors.

No fewer than 6 recent cardiovascular outcomes trials in patients with T2DM have consistently found a significant reduction in risk of HF hospitalisations with SGLT2 inhibitors [1]. Recent guidelines from the ESC and other scientific societies recommend the use of SGLT2 inhibitors in patients with T2DM to reduce the risk of HF hospitalisations events.

VERTIS CV was a multicentre, randomised, placebo-controlled, event-driven trial including 8,246 patients with T2DM and established ASCVD. Of the participants, 24% had a history of HF, which is consistent with the 20-30% of patients with HF present in the general T2DM population. The primary endpoint was a composite of CV death, non-fatal myocardial infarction, and non-fatal stroke.

The event rate of the primary endpoint was 3.9 events per 100 patient-years in the ertugliflozin versus 4.0 events in the placebo group (HR 0.97; 95% CI 0.85-1.11; P<0.001 for non-inferiority). In accordance with this, some other endpoints were also not significantly different between the 2 arms, namely:

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    • CV death or HF hospitalisations: 2.3 versus 2.7 events per 100 patient-years (HR 0.88; P=0.11);
    • CV death: 1.8 versus 1.9 events per 100 patient-years (HR 0.92; P=0.39); and
    • renal composite: 0.9 versus 1.2 events per 100 patient-years (HR 0.81; P=0.08);

In contrast, the event rate of HF hospitalisation was significantly different: 0.7 versus 1.1 events per 100 patient-years (HR 0.70; P=0.006).

The prespecified endpoint of time to first HF hospitalisation was 30% lower in the ertugliflozin versus the placebo group (HR 0.70). Prior history of HF did not influence this effect of ertugliflozin (P for interaction 0.40), neither was this affected by pre-trial ejection fraction (P for interaction 0.15 in case of a cut-off of 45% for ejection fraction). Interestingly, the effect of ertugliflozin was significantly greater in patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m² and in patients with albuminuria (both P=0.04), and in those taking diuretics (P=0.02). A prespecified analysis of total events showed that also the number of first and recurrent HF hospitalisation (rate ratio 0.70; P=0.001) and the composite of HF hospitalisation and CV death (RR 0.83; P=0.011) were significantly different between the 2 arms.

These results provide additional evidence in support of current guidance from cardiology and diabetes societies that recommend the use of SGLT2 inhibitors in patients with T2DM to reduce the risk of HF hospitalisations events.

 

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   1. Cosentino F. Efficacy of ertugliflozin on heart failure-related events in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease: results of the VERTIS trial. Chronic HF session, ESC Congress 2020, 31 Aug.

 



Posted on 5 November 202017 May 2024