Butler Javed, McMullan Ciaran J, Anstrom Kevin J, Barash Irina, Bonaca Marc P, Borentain Maria, Corda Stefano, Ezekowitz Justin A, Felker G Michael, Gates Davis, Lam Carolyn S P, Lewis Eldrin F, Lindenfeld JoAnn, Mentz Robert J, O'Connor Christopher M, Ponikowski Piotr, Reddy Yogesh N V, Rosano Giuseppe M C, Saldarriaga Clara, Senni Michele, She Lilin, Teixeira Pedro Pinto, Udelson James, Urbinati Alessia, Vlajnic Vanja, Voors Adriaan A, Xing Aiwen, Patel Mahesh J, Zannad Faiez
Baylor Scott and White Research Institute, Dallas, TX, USA; University of Mississippi, Jackson, MS, USA.
Merck, Rahway, NJ, USA.
Lancet. 2025 Aug 29. doi: 10.1016/S0140-6736(25)01665-4.
Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening.
In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo. The primary composite endpoint was time to cardiovascular death or heart failure hospitalisation. Efficacy endpoints were assessed in the intention-to-treat population. Adverse events were assessed in all randomly assigned patients who received at least one dose of study drug (safety population). This trial is registered with ClinicalTrials.gov, NCT05093933, and is complete.
Between Nov 2, 2021, and Dec 21, 2023, 10 921 patients were screened and 6105 were randomly assigned: 3053 to vericiguat and 3052 to placebo. The median age was 68·0 years (IQR 61·0-75·0), 1440 (23·6%) patients were women, 4665 (76·4%) were men, 3934 (64·4%) were White, and 2899 (47·5%) had no previous hospitalisation for heart failure. During a median follow-up of 18·5 months (IQR 13·6-24·7), primary outcome events occurred in 549 (18·0%) patients in the vericiguat group and 584 (19·1%) patients in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·83-1·04]; p=0·22). As prespecified in the protocol, because the primary endpoint was not statistically significant, all analyses of secondary and exploratory endpoints are considered nominal. Cardiovascular death occurred in 292 (9·6%) patients in the vericiguat group and 346 (11·3%) patients in the placebo group (HR 0·83 [95% CI 0·71-0·97]). Hospitalisation for heart failure occurred in 348 (11·4%) patients in the vericiguat group and in 362 (11·9%) patients in the placebo group (HR 0·95 [95% CI 0·82-1·10]). Serious adverse events occurred in 717 (23·5%) of 3049 patients in the vericiguat group and 751 (24·6%) of 3049 patients in the placebo group. The most common adverse event was symptomatic hypotension (345 [11·3%] patients in the vericiguat group and 281 [9·2%] in the placebo group). All-cause death occurred in 377 (12·3%) patients in the vericiguat group and 440 (14·4%) patients in the placebo group (HR 0·84 [95% CI 0·74-0·97]).
Among patients with HFrEF and no recent worsening, vericiguat did not reduce the risk of a composite endpoint of time to cardiovascular death or heart failure hospitalisation. Fewer cardiovascular deaths were observed in the vericiguat group than in the placebo group.
Merck Sharp & Dohme (a subsidiary of Merck) and Bayer.
维立西呱适用于降低近期出现病情恶化事件的射血分数降低的心力衰竭（HFrEF）患者发生心血管死亡和因心力衰竭住院的风险。VICTOR试验的目的是评估维立西呱对近期无心力衰竭病情恶化的HFrEF患者的疗效。
在这项双盲、安慰剂对照的3期试验中，于36个国家的482个地点开展，年龄在18岁及以上的HFrEF患者（左心室射血分数≤40%），在随机分组前6个月内无心力衰竭住院或3个月内无门诊静脉使用利尿剂情况，使用带有交互式响应技术的干预随机系统将患者按1:1随机分配至口服维立西呱（目标剂量10 mg）或匹配的安慰剂组。主要复合终点为心血管死亡或心力衰竭住院时间。在意向性治疗人群中评估疗效终点。在所有接受至少一剂研究药物的随机分配患者（安全性人群）中评估不良事件。本试验已在ClinicalTrials.gov注册，编号为NCT05093933，且已完成。
在2021年11月2日至2023年12月21日期间，共筛选了10921例患者，6105例被随机分配：3053例至维立西呱组，3052例至安慰剂组。中位年龄为68.0岁（四分位间距61.0 - 75.0），1440例（23.6%）为女性，4665例（76.4%）为男性，3934例（64.4%）为白人，2899例（47.5%）既往无心力衰竭住院史。在中位随访18.5个月（四分位间距13.6 - 24.7）期间，维立西呱组549例（18.0%）患者和安慰剂组584例（19.1%）患者发生主要结局事件（风险比[HR] 0.93 [95%置信区间0.83 - 1.04]；p = 0.22）。如方案预先规定，由于主要终点无统计学显著性，所有次要及探索性终点分析均视为名义性分析。维立西呱组292例（9.6%）患者和安慰剂组346例（11.3%）患者发生心血管死亡（HR 0.83 [95%置信区间
0.71 - 0.97]）。维立西呱组348例（11.4%）患者和安慰剂组362例（11.9%）患者因心力衰竭住院（HR 0.95 [95%置信区间0.82 - 1.10]）。维立西呱组3049例患者中的
717例（23.5%）和安慰剂组3049例患者中的751例（24.6%）发生严重不良事件。最常见的不良事件是症状性低血压（维立西呱组345例[11.3%]患者，安慰剂组281例[9.2%]患者）。维立西呱组377例（12.3%）患者和安慰剂组440例（14.4%）患者发生全因死亡（HR 0.84 [95%置信区间0.74 - 0.97]）。
在近期无病情恶化的HFrEF患者中，维立西呱未降低心血管死亡或心力衰竭住院复合终点的风险。维立西呱组观察到的心血管死亡少于安慰剂组。
默克夏普&多贺美（默克子公司）和拜耳公司。
