从利奥西呱到vericiguat——浅谈VICTORIA研究的来龙去脉

A brief introduction of VICTORIA study:from riociguat to vericiguat

一氧化氮(nitric oxide,NO)-可溶性鸟苷酸环化酶(soluble guanylate cyclase,sGC)-环鸟苷酸(cyclic guanosine monophosphate,cGMP)途径是一条与心血管疾病密切相关的高度保守的信号通路。在心力衰竭和肺动脉高压患者中,炎症和内皮细胞功能障碍导致NO生物有效性降低,减少下游cGMP合成。sGC激动剂利奥西呱和vericiguat可通过依赖和不依赖NO的双重作用模式导致cGMP生成增多而发挥扩张血管、抗重构等作用。利奥西呱是治疗肺动脉高压和慢性肺血栓栓塞性肺动脉高压的重要药物。LEPHT研究和DILATE-1研究初步明确了利奥西呱在射血分数降低和保留的心力衰竭合并肺动脉高压患者中的安全性。SOCRATES-REDUCED研究和SOCRATES-PRESERVED研究初步明确了vericiguat在射血分数降低和保留的心力衰竭患者中的安全性。VICTORIA研究则充分证明vericiguat较标准治疗可以降低高危射血分数降低的心力衰竭患者心血管死亡或因心力衰竭住院的复合终点10%(HR=0.90,95%CI:0.82~0.98,P=0.02)。正在进行的VITALITY-HFpEF研究拟评价vericiguat在射血分数保留的心力衰竭患者中的有效性和安全性。期待进一步的研究结果能够帮助人们在征服心力衰竭和肺动脉高压这两种严重威胁人类健康的疾病中取得更大的胜利。

The nitric oxide(NO)-soluble guanylate cyclase(sGC)-cyclic guanosine monophosphate(cGMP)pathway is a highly conserved signaling pathway,which is closely related to cardiovascular diseases.In patients with heart failure and pulmonary hypertension,inflammation and endothelial dysfunction decrease the bioavailability of NO,which can reduce the generation of cGMP.The sGC stimulators riociguat and vericiguat can increase the production of cGMP through the dual action mode of dependent and independent of NO,which play the role of vasodilation and anti-remodeling.Riociguat is an important drug for treatment of pulmonary hypertension and chronic thromboembolic pulmonary hypertension.The LEPHT study and the DILATE-1 study clarified the safety of riociguat in patients with heart failure with reduced ejection fractions(HFrEF)and heart failure with preserved ejection fractions(HFpEF)with pulmonary hypertension.The SOCRATES-REDUCED and SOCRATES-PRESERVED studies clarified the safety of vericiguat in patients with HFrEF and HFpEF.The VICTORIA study proved that vericiguat can reduce the incidence of death from cardiovascular causes or rehospitalization for heart failure by 10%(HR=0.90,95%CI:0.82~0.98,P=0.02)in highrisk HFrEF patients compared to standard treatment.The ongoing VITALITY-HFpEF study intends to evaluate the effectiveness and safety of vericiguat in HFpEF patients.We hope that further research can help us to achieve greater victory in heart failure and pulmonary hypertension.