Abstract：
BACKGROUND: Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with heart failure reduced ejection fraction (HFrEF). This study aimed to assess the relative efficacy of vericiguat and sacubitril/valsartan through a systematic review, network meta-analysis, and non-inferiority tests.
METHODS: A systematic review was conducted to identify the randomized phase 3 clinical trials involving vericiguat and sacubitril/valsartan. The hazard ratios (HRs) with 95% confidence intervals (CI) for cardiovascular death (CVD) and hospitalization due to HF (hHF) were extracted from these trials and synthesized via network meta-analysis. Non-inferiority testing of vericiguat was performed using a fixed-margin method with a predefined non-inferiority margin (1.24). Sensitivity analyses explored the impact of the time from hHF to screening.
RESULTS: Among the 1366 studies, two trials (VICTORIA and PARADIGM-HF) met the inclusion criteria. Network meta-analysis demonstrated that the HR for CVD or hHF with vericiguat did not significantly differ from that for sacubitril/valsartan (HR: 0.88, 95% CI:0.62-1.23). The upper limit of the 95% CI was less than the predefined margin of 1.24, confirming vericiguat\'s non-inferiority to sacubitril/valsartan. Sensitivity analyses affirmed the robustness of the base-case results.
CONCLUSIONS: Vericiguat exhibited a comparable risk of CVD or hHF when contrasted with sacubitril/valsartan. Importantly, in patients with HFrEF, vericiguat\'s efficacy was not statistically inferior to that of sacubitril/valsartan. These findings reinforce the potential of vericiguat as a viable treatment option for this patient population.
METHODS: A systematic review was conducted to identify the randomized phase 3 clinical trials involving vericiguat and sacubitril/valsartan. The hazard ratios (HRs) with 95% confidence intervals (CI) for cardiovascular death (CVD) and hospitalization due to HF (hHF) were extracted from these trials and synthesized via network meta-analysis. Non-inferiority testing of vericiguat was performed using a fixed-margin method with a predefined non-inferiority margin (1.24). Sensitivity analyses explored the impact of the time from hHF to screening.
RESULTS: Among the 1366 studies, two trials (VICTORIA and PARADIGM-HF) met the inclusion criteria. Network meta-analysis demonstrated that the HR for CVD or hHF with vericiguat did not significantly differ from that for sacubitril/valsartan (HR: 0.88, 95% CI:0.62-1.23). The upper limit of the 95% CI was less than the predefined margin of 1.24, confirming vericiguat\'s non-inferiority to sacubitril/valsartan. Sensitivity analyses affirmed the robustness of the base-case results.
CONCLUSIONS: Vericiguat exhibited a comparable risk of CVD or hHF when contrasted with sacubitril/valsartan. Importantly, in patients with HFrEF, vericiguat\'s efficacy was not statistically inferior to that of sacubitril/valsartan. These findings reinforce the potential of vericiguat as a viable treatment option for this patient population.
摘要：
背景：尽管与安慰剂相比，Vericiguat的疗效已经确立，对于心力衰竭射血分数降低(HFrEF)患者,其与沙库巴曲/缬沙坦的比较疗效仍不确定.本研究旨在通过系统评价评价维利古特和沙库巴曲/缬沙坦的相对疗效。网络荟萃分析，和非劣效性测试。
方法：进行了系统评价，以确定涉及Vericiguat和沙库巴曲/缬沙坦的随机3期临床试验。从这些试验中提取心血管死亡（CVD）和HF住院（hHF）的风险比（HRs）和95%置信区间（CI），并通过网络荟萃分析进行合成。使用具有预定义的非劣效性边缘（1.24）的固定边缘方法对vericiguat进行非劣效性测试。敏感性分析探讨了从hHF到筛查的时间的影响。
结果：在1366项研究中，两项试验(VICTORIA和PARADIGM-HF)符合纳入标准.网络荟萃分析表明，使用vericiguat的CVD或hHF的HR与沙库巴曲/缬沙坦的HR没有显着差异（HR：0.88，95％CI：0.62-1.23）。95%CI的上限小于1.24的预定界限，证实了Vericiguat对沙库巴曲/缬沙坦的非劣效性。敏感性分析证实了基本情况结果的稳健性。
结论：Vericiguat与沙库巴曲/缬沙坦相比，显示出相当的CVD或hHF风险。重要的是,在HFrEF患者中，Vericiguat的疗效在统计学上不低于沙库巴曲/缬沙坦。这些发现加强了Vericiguat作为该患者人群的可行治疗选择的潜力。
方法：进行了系统评价，以确定涉及Vericiguat和沙库巴曲/缬沙坦的随机3期临床试验。从这些试验中提取心血管死亡（CVD）和HF住院（hHF）的风险比（HRs）和95%置信区间（CI），并通过网络荟萃分析进行合成。使用具有预定义的非劣效性边缘（1.24）的固定边缘方法对vericiguat进行非劣效性测试。敏感性分析探讨了从hHF到筛查的时间的影响。
结果：在1366项研究中，两项试验(VICTORIA和PARADIGM-HF)符合纳入标准.网络荟萃分析表明，使用vericiguat的CVD或hHF的HR与沙库巴曲/缬沙坦的HR没有显着差异（HR：0.88，95％CI：0.62-1.23）。95%CI的上限小于1.24的预定界限，证实了Vericiguat对沙库巴曲/缬沙坦的非劣效性。敏感性分析证实了基本情况结果的稳健性。
结论：Vericiguat与沙库巴曲/缬沙坦相比，显示出相当的CVD或hHF风险。重要的是,在HFrEF患者中，Vericiguat的疗效在统计学上不低于沙库巴曲/缬沙坦。这些发现加强了Vericiguat作为该患者人群的可行治疗选择的潜力。
