Farber Harrison W, Miller Dave P, Meltzer Leslie A, McGoon Michael D
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts.
J Heart Lung Transplant. 2013 Nov;32(11):1114-22. doi: 10.1016/j.healun.2013.08.010. Epub 2013 Sep 10.
Current guidelines recommend intravenous prostacyclin as first-line therapy for patients with pulmonary arterial hypertension (PAH) in New York Heart Association/World Health Organization functional class (FC) IV, or combination therapy for patients in any FC who do not respond to monotherapy. We investigated the aggressiveness of therapy in patients enrolled in the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) Registry who deteriorated to FC IV or died.
Among 3,515 patients (age ≥ 18 years) in REVEAL with a mean pulmonary artery pressure ≥ 25 mm Hg and pulmonary capillary wedge pressure ≤ 15 mm Hg, we examined three sub-sets: the 487 patients who had a PAH-related death, the larger set of 908 patients who died from any cause (PAH-related, not PAH-related, or unknown), and the 294 patients who were FC I, II, or III at enrollment and later assessed as FC IV.
Among patients who died, 56% (n = 272 of 487) and 43% (n = 391 of 908) were receiving intravenous prostacyclin before death in the PAH-related death and all-cause death cohorts, respectively. In the PAH-related death cohort, 60% and 16% of patients were most recently assessed as FC III and IV, respectively; among those assessed as FC IV within 6 months of death, 57.7% (n = 15 of 26) had received intravenous prostacyclin. Because many patients died without an observed assessment of worsening to FC IV, we also evaluated medication use among the cohort of patients who worsened to FC IV during the study. One day before worsening to FC IV, 150 of 294 patients were not receiving intravenous prostacyclin and 70 were receiving only PAH-specific monotherapy; of these, 61% and 67%, respectively, received no additional therapy 90 days later.
Intravenous prostacyclin and combination therapy are not consistently used in the most seriously ill patients enrolled in REVEAL after being assessed as FC IV or at the time of death.
当前指南推荐，对于纽约心脏协会/世界卫生组织功能分级（FC）为IV级的肺动脉高压（PAH）患者，静脉应用前列环素作为一线治疗；对于任何功能分级且单药治疗无效的患者，则采用联合治疗。我们调查了参加REVEAL（评估PAH疾病早期和长期管理注册研究）注册研究且病情恶化至FC IV级或死亡患者的治疗积极性。
在REVEAL研究中，纳入3515例年龄≥18岁、平均肺动脉压≥25 mmHg且肺毛细血管楔压≤15 mmHg的患者，我们研究了三个亚组：487例PAH相关死亡患者、908例任何原因死亡（PAH相关、非PAH相关或原因不明）的更大组患者，以及294例入组时为FC I、II或III级且后来评估为FC IV级的患者。
在死亡患者中，PAH相关死亡队列和全因死亡队列中分别有56%（487例中的272例）和43%（908例中的391例）在死亡前接受静脉前列环素治疗。在PAH相关死亡队列中，分别有60%和16%的患者最近评估为FC III级和IV级；在死亡前6个月内评估为FC IV级的患者中，57.7%（26例中的15例）接受了静脉前列环素治疗。由于许多患者死亡时未观察到病情恶化为FC IV级的评估，我们还评估了研究期间病情恶化为FC IV级的患者队列中的用药情况。在恶化为FC IV级的前一天，294例患者中有150例未接受静脉前列环素治疗，70例仅接受PAH特异性单药治疗；其中，90天后分别有61%和67%的患者未接受额外治疗。
在REVEAL研究中，病情评估为FC IV级或死亡的最重症患者中，静脉前列环素和联合治疗的应用并不一致。
