Efficacy of vericiguat in HFrEF consistent across multiple guideline-recommended therapies
An analysis of the VICTORIA trial showed that the benefits of vericiguat in HF with reduced ejection fraction was consistent across various background therapies for HFrEF, a speaker reported.
However, according to findings presented at the virtual Heart Failure Society of America Scientific Meeting, the treatment effect of vericiguat (Merck/Bayer) among patients on at least 50% of the target dose for beta-blockers may warrant further investigation.
As Healio previously reported, in the primary findings of the VICTORIA trial, presented at the American College of Cardiology Scientific Session, vericiguat reduced CV death and HF hospitalization compared with placebo in high-risk patients with HFrEF.
“Patients in VICTORIA were on excellent background medical therapy. The doses of standard of care medications for those on triple therapy was very good,” Justin Ezekowitz, MBBCh, MSc, professor in the department of medicine in the division of cardiology at the University of Alberta, Canada, said during his presentation. “The treatment effect of vericiguat compared to placebo on the primary composite endpoint was consistent across standard-of-care medication classes with an association of treatment effect for those with greater than 50% of target doses for beta-blockers is worthy of further consideration and exploration.”
For this analysis, investigators included 5,040 patients in the VICTORIA trial with data on HFrEF standard-of-care medications. These medications included renin-angiotensin system blockers (ACE inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors), beta-blockers and mineralocorticoid receptor antagonists. Researchers evaluated the impact of dose-corrected adherence to standard care medications on the treatment effect of vericiguat among patients with HFrEF.
Patients were also stratified by the number of medications they were taking (zero to one, double or triple therapy). Researchers observed that patients on triple therapy were younger (mean age, 74 vs. 71 vs. 66 years, respectively), had higher median estimated glomerular filtration rates (39.4 vs. 52.2 vs. 63 mL/min/1.73 m2, respectively) and lower median N-terminal pro-B-type natriuretic peptide levels (4,065 vs. 3,240 vs. 2,532 pg/mL, respectively).
Regardless of adherence, the treatment effect of vericiguat compared with placebo was consistent for patients also prescribed ACE inhibitors and angiotensin receptor blockers (P for interaction = .71), angiotensin receptor-neprilysin inhibitors (P for interaction = .361), renin-angiotensin system blockers (P for interaction = .825), mineralocorticoid receptor antagonists (P for interaction = .431) and triple therapy (P for interaction = .147).
However, researchers found a significant association between dose-corrected adherence to beta-blockers and the treatment effects of vericiguat, with those taking at least 50% of the target dose of beta-blockers benefiting more from vericiguat than those who were not (P for interaction = .001).
“We had a limited number of patients on an SGLT2 inhibitor, as this was the not yet the global trend,” Ezekowitz said during the presentation. “We also used target doses restricted to medications with an evidence base or with guideline recommendations.”
“The importance of this study is that it allows us now to examine the effects of vericiguat relative to other therapies that we prescribe to our patients that have been proven to reduce risk,” James Januzzi Jr., MD, FACC, FESC, Hutter Family Professor of Medicine at Harvard Medical School and cardiac physician at Massachusetts General Hospital, said during a discussant presentation. “It is increasingly important to understand the background [of guideline-directed medical therapy] when evaluating new drugs and devices, given how increasingly crowded the playing field is. Standardization of this definition would also allow a better understanding of cross-trial comparison.
“Lastly, clinicians are faced with an increasingly crowded set of choices, which leads to uncertainty regarding which therapies should be used, when they should be used and in whom they should be used,” Januzzi said during his presentation. “This leads to unacceptable gaps in real-world administration of guideline-directed medical therapy. The VICTORIA investigators are to be congratulated in showing us that vericiguat actually exerts benefit across the wide range of guideline-directed medical therapies that are prescribed to our patients, providing reassuring information for clinicians who might be contemplating utilizing these agents.”
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Ezekowitz JA, et al. Late-breaking clinical trials II. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 30-Oct. 6, 2020 (virtual meeting).