{"id":138893,"date":"2025-08-31T14:48:09","date_gmt":"2025-08-31T18:48:09","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=138893"},"modified":"2026-01-28T15:04:43","modified_gmt":"2026-01-28T20:04:43","slug":"victor-vericiguat-did-not-meet-primary-endpoint-but-reduced-cv-death-in-stable-ambulatory-hfref","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=138893","title":{"rendered":"VICTOR: Vericiguat Did Not Meet Primary Endpoint But Reduced CV Death in Stable, Ambulatory HFrEF"},"content":{"rendered":"<p><b>Key Points:<\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The VICOTRIA trial previously demonstrated that vericiguat reduced the risk of\u00a0 heart failure (HF) hospitalization or cardiovascular (CV) death in patients with recently decompensated HFrEF.<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The current VICTOR trial evaluated vericiguat vs placebo among those with stable, ambulatory HFrEF.\u00a0<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Although there was no significant difference in the primary endpoint of CV death or HF hospitalization, vericiguat significantly reduced CV death as well as overall worsening heart failure events in prespecified secondary analyses.\u00a0<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">These findings suggests a positive impact of vericiguat on those with compensated, ambulatory HFrEF receiving contemporary guideline directed medical therapy (GDMT).\u00a0\u00a0<\/span><\/li>\n<\/ul>\n<p><!--more--><\/p>\n<p><span style=\"font-weight: 400;\">Based on the VICTORIA trial, the FDA approved vericiguat, an oral soluble guanylate cyclase stimulator, in 2021 to reduce the risk of CV death and HF hospitalization among adults with an ejection fraction (EF) less than 45% and a recent worsening HF event (i.e. recent HF hospitalization or need for outpatient IV diuretics).<\/span><span style=\"font-weight: 400;\">1<\/span><span style=\"font-weight: 400;\"> However, the effect of vericiguat on stable, ambulatory HFrEF patients without a worsening HF event is unknown.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">On August 30<\/span><span style=\"font-weight: 400;\">th<\/span><span style=\"font-weight: 400;\"> 2025, the results of \u201cVericiguat in patients with chronic heart failure and reduced ejection fraction (<\/span><a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(25)01665-4\/abstract?rss=yes\"><span style=\"font-weight: 400;\">VICTOR<\/span><\/a><span style=\"font-weight: 400;\">): a double-blind, placebo-controlled, randomized, phase 3 trial\u201d were presented at the European Society of Cardiology Congress, with simultaneous publication in the <\/span><i><span style=\"font-weight: 400;\">Lancet<\/span><\/i><span style=\"font-weight: 400;\">.\u00a0 The purpose was to assess the effect of vericiguat in patients with stable, ambulatory HFrEF without a recent worsening heart failure event.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">This multinational trial randomized patients age &gt;18 years with NYHA Class II-IV HF and\u00a0 EF \u2264 40%, NT-proBNP levels between 600-6000 pg\/mL, and on stable background GDMT to vericiguat (titrated to a target dose of 10mg) or placebo once daily. Importantly, patients with HF hospitalization within the prior 6 months or outpatient IV diuretic use within 3 months were excluded. The primary endpoint was a composite of CV death or HF hospitalization. Hierarchically tested secondary endpoints included a powered endpoint for CV death, as well as total worsening HF events (including both outpatient and inpatient episodes).<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Overall, 6105 patients were randomized. The mean age was 67 years; 23.5% were female, 64.5% were white, the mean EF was ~30%, and nearly half had never had a prior HF hospitalization. The group was well treated at baseline: 70% were on loop diuretics, one-third had an ICD, and background GDMT was robust. After a median follow up of 18.5 months, the primary outcome occurred in 18.0% in the vericiguat group vs. 19.1% in the placebo group (HR 0.93 [95% CI 0.83-1.04]; p =0.22). While there was no effect of vericiguat on HF hospitalizations alone, there was a significant reduction in overall worsening HF events (HR 0.90 [95% CI 0.81-1.00]; p =0.047). Importantly, vericiguat was also associated with a decrease in CV death (HR 0.83 [95% CU 0.71-0.97]; p=0.02), with consistent numerical reductions in all-cause death, sudden death, and death due to heart failure.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Prof Faiez Zannad, MD, PhD of Universit\u00e9 de Lorraine, France, concluded: \u201dVericiguat did not reduce the risk of the composite of CV death or heart failure hospitalization in ambulatory patients with HFrEF on a background of high use of contemporary GDMT. However in a pre-specified, powered secondary analysis vericiguat was associated with a significantly reduced risk of CV death\u2026and although vericiguat did not achieve significant reduction in traditional heart failure hospitalizations, pre-specified exploratory analyses demonstrated a clinically meaningful reduction in the overall risk of worsening HF when considering the entire patient journey. The totality of evidence suggests favorable effects of vericiguat on compensated outpatients with HFrEF.\u201d\u00a0<\/span><\/p>\n<ol>\n<li><span style=\"font-weight: 400;\">Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. <\/span><i><span style=\"font-weight: 400;\">N Engl J Med<\/span><\/i><span style=\"font-weight: 400;\">. 2020;382(20):1883-1893. doi:10.1056\/NEJMoa1915928<\/span><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Key Points: The VICOTRIA trial previously demonstrated that vericiguat reduced the risk of\u00a0 heart failure (HF) hospitalization or cardiovascular (CV) death in patients with recently decompensated HFrEF. The current VICTOR trial evaluated vericiguat vs placebo among those with stable, ambulatory HFrEF.\u00a0 Although there was no significant difference in the primary endpoint of CV death or [&hellip;]<\/p>\n","protected":false},"author":40618,"featured_media":4881,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[900,8],"tags":[45,901,47,185],"ppma_author":[1072],"class_list":{"0":"post-138893","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-esc-2025","8":"category-news","9":"tag-conference","10":"tag-esc2025","11":"tag-featured","12":"tag-news","13":"author-lucas-marinacci-md"},"authors":[{"term_id":1072,"user_id":40618,"is_guest":0,"slug":"lucas-marinacci-md","display_name":"Lucas Marinacci MD","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/cd81d2064c6f6263719c24aeb738faf718e9bd869c5a840718bc535238ae72f6?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138893","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40618"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=138893"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138893\/revisions"}],"predecessor-version":[{"id":138894,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138893\/revisions\/138894"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/4881"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=138893"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=138893"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=138893"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=138893"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}