Relationship Between Time From Diagnosis and Morbidity/Mortality in Pulmonary Arterial Hypertension

Abstract

BACKGROUND: Early initiation of pulmonary arterial hypertension (PAH) therapies is associated with improved long-term outcomes, yet data on the early use of prostacyclin pathway agents are limited. In these post hoc analyses of the Prostacyclin (PGI 2 ) Receptor Agonist In Pulmonary Arterial Hypertension (GRIPHON) study, the largest randomized controlled trial for PAH to date, the prognostic value of time from diagnosis and its impact on treatment response were examined.RESEARCH QUESTION: How does time from diagnosis impact morbidity/mortality events and response to selexipag treatment in patients with PAH?STUDY DESIGN AND METHODS: The GRIPHON study randomly assigned 1,156 patients with PAH to selexipag or placebo treatment. Patients were categorized post hoc into a time from diagnosis of # 6 months and > 6 months at randomization. Hazard ratios (selexipag vs placebo) were calculated for the primary end point of morbidity/mortality by time from diagnosis using Cox proportional hazard models.RESULTS: Time from diagnosis was # 6 months in 34.9% and > 6 months in 65.1% of patients. Time from diagnosis was prognostic of morbidity/mortality, with newly diagnosed patients having a poorer long-term outcome than patients diagnosed for longer. Compared with placebo, selexipag reduced the risk of morbidity/mortality in patients with a time from diagnosis of # 6 months and > 6 months, with a more pronounced effect in newly diagnosed patients (hazard ratio, 0.45 [95% CI, 0.33-0.63] and 0.74 [95% CI, 0.57-0.96], respectively; P ¼ .0219 for interaction). INTERPRETATION:In the GRIPHON study, newly diagnosed PAH patients had a worse prognosis than patients with a longer time from diagnosis. The benefit of selexipag treatment on disease progression was more pronounced in patients treated earlier than in patients treated later.

Pulmonary Arterial Hypertension: Regional Health Care Opportunities

“…1. пациенты с идиопатической ЛАГ, наличием ответа на острые тесты вазореактивности, слабой выраженностью симптомов и близкими к норме показателями переносимости физической нагрузки, сДЛА и ЛСС на фоне высоких доз блокаторов кальциевых чившем 1156 пациентов (группа селексипага -574 пациента), ЛАГ-монотерапия селексипагом или последовательная комбинированная (двойная и даже тройная) специфическая терапия с добавлением селексипага снижала время до наступления первого события, ассоциированного с ЛАГ, или смерти пациента на 40% (отношение рисков (ОР) 0,60; 99% ДИ 0,46-0,78; p<0,001) [7]. Эффективность селексипага не зависела от того, применялся ли препарат в качестве монотерапии (ОР = 0,57; 99% ДИ 0,32-1,03) или в комбинации с другими специфическими препаратами.…”

“…Эффективность селексипага не зависела от того, применялся ли препарат в качестве монотерапии (ОР = 0,57; 99% ДИ 0,32-1,03) или в комбинации с другими специфическими препаратами. К концу двойного слепого периода (26 недель) отмечено снижение смертности и частоты госпитализаций в связи с ухудшением течения ЛАГ на 30% (ОР = 0,70; 95% ДИ 0,54 до 0,91; р = 0,003) [7]. Данные открытой фазы исследования GRIPHON, представленные Galie N с соавт.…”

Time Is of the Essence in PAH Therapy

“…1 Whether initial treatment has to include a prostacyclin analog remains, however, an open debate. 12 In summary, this is a clearly valuable and provocative post hoc analysis by Gaine et al 9 of the large landmark GRIPHON trial investigating the impact of time from diagnosis to initiation of selexipag on morbidity and mortality. The authors' conclusions are consistent with prior reports that incident PAH patients have worse long-term outcomes compared with prevalent patients and that starting a PAH drug early, in this case, selexipag (whether in incident or prevalent patients), positively affects long-term outcomes.…”

“…[4][5][6][7][8] However, timing of treatment initiation and drug choice remain critical in tackling a disease with unacceptably high morbidity and mortality. 3 In this issue of CHEST, Gaine and colleagues 9 addressed an interesting question, whether early is better than delayed treatment with, in this case, selexipag, an oral prostacyclin receptor (IP receptor) agonist. In a post hoc analysis of one of the largest randomized controlled clinical trials in PAH to date, GRIPHON, 6 the authors investigated the impact of time from diagnosis to selexipag initiation on morbidity and mortality.…”

Upfront Combination Therapy for Pulmonary Arterial Hypertension: Time to Be More Ambitious than AMBITION

“…Real-world data suggest that a minority of patients treated with upfront oral combination therapy reach low-risk status ( 5 ). At the same time, there is ample evidence that the timing of therapies matter—treatments are more efficacious early ( 6 ), mortality is higher in incident versus prevalent patients ( 7 ), clinical worsening that may trigger escalation is associated with increased mortality ( 8 ), and, most disconcerting, the functional capacity of the placebo group in open-label extensions of randomized controlled trials (RCTs) that receive therapy just 12–16 weeks later never catch up ( 9 ).…”