Department of Pulmonary Medicine, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
Respir Res. 2023 Sep 15;24(1):223. doi: 10.1186/s12931-023-02531-1.
Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients.
To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH.
We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response.
Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response.
Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies.
在肺动脉高压（PAH）中，实现并维持低风险状态与良好的预后相关。治疗对风险状态的影响在患者之间存在差异。
确定可能预测磷酸二酯酶-5 抑制剂（PDE-5i）治疗 PAH 反应的变量。
我们对西班牙 PAH 登记处的 830 例 PAH 患者进行了队列分析，这些患者诊断为 PAH 并开始接受 PDE5i 治疗，且随访时间超过 1 年。644 例患者开始 PDE-5i 单药或联合治疗，186 例患者开始 PDE-5i 联合内皮素受体拮抗剂（ERA）治疗。如果患者在 1 年内：（1）存活；（2）未出现临床恶化；（3）欧洲心脏病学会/欧洲呼吸学会（ESC/ERS）风险评分改善或仍处于低危状态，则被认为是有反应者。使用单变量和多变量逻辑回归模型分析与有利反应相关的变量。
210 例（33%）单独开始 PDE-5i 治疗的患者被归类为有反应者，无论单药治疗还是联合治疗。除了 PAH 结局的已知预测因素（基线时为低危、年龄较小）外，男性、肝肺高血压（PoPH）或 HIV-PAH 的诊断是 PDE-5i 治疗有利反应的独立预测因素。一氧化碳弥散量（DLco）≤预测值的 40%与不良反应相关。当 PDE-5i 作为一线联合治疗时，58%的患者有反应。在这一组中，特发性 PAH（IPAH）的诊断是有利反应的独立预测因素，而结缔组织病-PAH 与不良反应相关。
男性、PoPH 或 HIV-PAH 的诊断是 PDE-5i 作为单药或联合治疗时对风险状态产生有利影响的预测因素。IPAH 患者在一线联合治疗时对 PDE-5i 的反应更有利。这些结果确定了可能对 PDE-5i 单药治疗有反应的患者特征，以及可能从替代治疗策略中受益的患者特征。
