Victoria Trial: Vericiguat Joins the Big League, or Does it?

Abstract

The VICTORIA trial showed Vericiguat once daily (titrated up to 10 mg) significantly reduced its primary end-point, the composite of death from cardiovascular causes or first hospitalization for heart failure, in 5050 class II-IV HFrEF patients (LVEF<45%). This a land-mark trial, one of the largest we have seen in heart failure, and it had some very important novel features; it only recruited patients with a recent (within 6 months) worsening of their heart failure, a group known to be at increased risk of subsequent events, and it included more severe heart failure than most recent trials with NTproBNP levels nearly twice that of Paradigm-HF or DAPA-HF. VICTORIA had substantially higher mortality rate but an apparently less impressive hazard ratio (HR) 0.90 (0.82 – 0.98) compared to Paradigm’s 0.80 (0.73 – 0.87) and DAPA’s 0.74 (0.65 –0.85). This must be considered against a healthy absolute risk reduction at 4.2% compared to Paradigm’s 2.7% and DAPA’s 4.0%, due to the higher risk patients in VICTORIA. Another very important difference with VICTORIA is that it included the higher risk recently discharged HF patients, and patients eGFR’s down to 15 ml per minute per 1.73 m2 of body-surface area, possibly suggesting a special place for Vericiguat in traetring these at-risk subsets of HFrEF patients, but for the fact that the cohort between 15 and 30mL/min/1.73m2 of eGFR was only around 10.0%, and the point estimate for the HR for this small group was above 1.0 at 1.06 (0.83-1.34). Aslo the sub-grouping by NTproBNP level was highly significantly interacting (p<0.001) with the lower three quartiles all being significantly in favour of Vericiguat and the highest quartile (>5,314 pg/mL) being almost significantly worse on Vericiguat with a HR of 1.16 (0.99-1.35). So the two major areas where Vericiguat may have received special notice appear to be less impressive when we look in detail at the trial results. How do we therefore place Vericiguat in the wake of VICTORIA? It is a proven therapy in a disease which still has residual high rates of clinical mortality and morbidity. It conveyed a benefit on top of other therapies, thus it should be not ignored and may indeed be a very effective therapy in some patients.