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

Andrew Coats


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.


Heart Failure; vericiguat; randomised controlled trial

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Tolppanen H, Ponikowski P. sGC Stimulators and Activators. International Cardiovascular Forum Journal. 2019;18:609.2-6 DOI: 10.17987/icfj.v18i0.609 accessed, Jan 5 2020

Armstrong, PW, Pieske, B, Anstrom, KJ, et al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. New England Journal of Medicine 2020;

DOI: 10.1056/NEJMoa1915928

Coats AJS. Vericiguat for heart failure and the VICTORIA trial - the dog that didn't bark? Eur J Heart Fail. 2020 Mar 1. doi: 10.1002/ejhf.1778. PMID: 32115834

Butler J, Anstrom KJ, Armstrong PW, for the VICTORIA Study Group. Comparing the Benefit Of Novel Therapies Across Clinical Trials: Insights from the VICTORIA Trial. Circ. 2020 (in press) DOI: 10.1161/CIRCULATIONAHA.120.047086

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. doi: 10.1056/NEJMoa1409077.

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995-2008. doi: 10.1056/NEJMoa1911303.

Rosano GMC, Ponikowski P. Myosin Activators. International Cardiovascular Forum Journal. 2019;18:7-10. DOI: 10.17987/icfj.v18i0.611

Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, Legg JC, Büchele G, Varin C, Kurtz CE, Malik FI, Honarpour N. Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF. JACC Heart Fail. 2020 Feb 4. pii: S2213-1779(20)30002-0. doi: 10.1016/j.jchf.2019.12.001.

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2 DOI: 10.17987/icfj.v2i1.4


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