Benza Raymond L, Boucly Athénaïs, Farber Harrison W, Frost Adaani E, Ghofrani Hossein-Ardeschir, Hoeper Marius M, Lambelet Marc, Rahner Claudia, Bansilal Sameer, Nikkho Sylvia, Meier Christian, Sitbon Olivier
Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
J Heart Lung Transplant. 2022 Mar;41(3):411-420. doi: 10.1016/j.healun.2021.10.013. Epub 2021 Oct 28.
Risk assessment is essential in pulmonary arterial hypertension (PAH) management. We investigated the effect of riociguat on REVEAL Lite 2 score, an abridged version of the REVEAL risk score, and its association with long-term outcomes in PATENT.
PATENT-1 was a randomized, double-blind study of riociguat vs placebo in patients with PAH. In the PATENT-2 open-label extension, all patients received riociguat up to 2.5 mg three times daily (n = 396). REVEAL Lite 2 scores were calculated at baseline, PATENT-1 Week 12, and PATENT-2 Week 12, with patients stratified as low- (1-5), intermediate- (6-7), or high-risk (≥8). Kaplan-Meier and Cox proportional hazards analyses assessed association of riociguat with survival and clinical worsening-free survival (CWFS).
REVEAL Lite 2 score improved with riociguat 2.5 mg at PATENT-1 Week 12 (least-squares mean difference vs placebo: -0.8; p = 0.0004). More patients receiving riociguat 2.5 mg stabilized or improved risk stratum at PATENT-1 Week 12 vs placebo (p = 0.0005) and achieved low-risk status. REVEAL Lite 2 score at baseline and PATENT-1 Week 12 were associated with survival and CWFS (all p < 0.0001), as was change in score from baseline to Week 12 (p = 0.0002 and p < 0.0001, respectively). Survival and CWFS differed between risk strata at baseline (p < 0.0001) and PATENT-1 Week 12 (p < 0.0001).
This analysis confirms the risk-reduction benefits of riociguat in patients with PAH and further contributes to the validation of REVEAL Lite 2 in facilitating PAH risk assessment.
风险评估在肺动脉高压（PAH）管理中至关重要。我们研究了利奥西呱对REVEAL Lite 2评分（REVEAL风险评分的简化版）的影响及其与PATENT研究中长期结局的关联。
PATENT-1是一项利奥西呱与安慰剂对比治疗PAH患者的随机、双盲研究。在PATENT-2开放标签扩展研究中，所有患者接受利奥西呱治疗，剂量为每日三次，每次2.5毫克（n = 396）。在基线、PATENT-1研究的第12周和PATENT-2研究的第12周计算REVEAL Lite 2评分，患者被分为低风险（1 - 5分）、中度风险（6 - 7分）或高风险（≥8分）。采用Kaplan-Meier法和Cox比例风险分析评估利奥西呱与生存及无临床恶化生存（CWFS）的关联。
在PATENT-1研究的第12周，利奥西呱2.5毫克组的REVEAL Lite 2评分有所改善（与安慰剂相比的最小二乘均值差异：-0.8；p = 0.0004）。与安慰剂相比，更多接受利奥西呱2.5毫克治疗的患者在PATENT-1研究的第12周风险分层稳定或改善（p = 0.0005）并达到低风险状态。基线及PATENT-1研究第12周的REVEAL Lite 2评分与生存及CWFS相关（所有p < 0.0001），从基线到第12周评分的变化也与之相关（分别为p = 0.0002和p < 0.0001）。基线时及PATENT-1研究第12周不同风险分层的生存及CWFS存在差异（p < 0.0001）。
该分析证实了利奥西呱对PAH患者降低风险的益处，并进一步有助于验证REVEAL Lite 2在促进PAH风险评估方面的作用。
