Pulmonary vasodilator therapy in sarcoidosis‐associated pulmonary hypertension may decrease lung function decline and mortality

Abstract

The efficacy of treating sarcoidosis‐associated pulmonary hypertension (SAPH) with pulmonary vasodilator therapy is unclear. The INCREASE trial showed improvement in 6‐minute walk distance (6MWD) and in decline in functional vital capacity (FVC) in patients with interstitial lung disease and pulmonary hypertension. We hypothesize that patients with SAPH treated with pulmonary vasodilators have reduced decline in FVC. We retrospectively analyzed patients with SAPH who underwent lung transplantation evaluation. The primary objective was to compare change in FVC between patients with SAPH who received pulmonary vasodilators (treated) and those who did not (untreated). Secondary objectives were to compare the change in 6MWD, change in oxygen requirement, transplant rates, and mortality between treated and untreated SAPH patients. We identified 58 patients with SAPH; 38 patients received pulmonary vasodilator therapy, and 20 patients did not. Treated SAPH patients had significantly less decline in FVC than untreated SAPH patients (+54 mL vs. −357 mL, p < 0.01). Treated SAPH patients had significantly higher survival than untreated SAPH patients. Receiving PH therapy was significantly associated with a change in FVC (estimate 0.36 ± 0.07, p < 0.01) and decreased mortality (hazard ratio 0.29, confidence interval 0.12–0.67, p < 0.01). Among patients with SAPH, those who received pulmonary vasodilator therapy had significantly less decline in FVC and increased survival. Receiving pulmonary vasodilator therapy was significantly associated with FVC change and decreased mortality. These study findings point towards potential benefit of pulmonary vasodilator therapy in SAPH patients. Further prospective studies are required to fully elucidate the benefits of pulmonary vasodilator therapy in SAPH.

Pulmonary hemodynamics and transplant‐free survival in sarcoidosis‐associated pulmonary hypertension: Results from an international registry

“…Of note, a recent retrospective study found that pulmonary vasodilator therapy was associated with reduced risk of mortality among patients with SAPH. 8 Given these varying findings, the indications for treatment of SAPH and specific treatment regimens have not been standardized, though the 2022 World Association of Sarcoidosis and other Granulomatous Disorders statement on the diagnosis and management of SAPH does advocate for consideration of treatment of SAPH with pulmonary vasodilator therapy in appropriate patients under the management of a multidisciplinary team. 2 , 9 Coexistent cardiac sarcoidosis can impact both LV and right ventricular function, which can in turn lead to the develop of SAPH.…”

Pulmonary Vasodilator Therapy Is Associated with Decreased Mortality in Patients with Chronic Lung Disease and Severe Pulmonary Hypertension

“…Gayen et al (2023) had similar findings in a retrospective study that demonstrated improved survival with PAH-specific therapy in sarcoidosis-associated PH; all patients had pulmonary fibrosis due to sarcoidosis [ 11 ]. The treated group, on average, met the ESC/ERS definition of severe PH with a mean PVR of 6.6 WU compared to non-severe PH in the untreated group with a mean PVR of 3.8 WU.…”

Phenotypes of Sarcoidosis-Associated Pulmonary Hypertension—A Challenging Mystery

“…The results of three phase 2 studies are awaited: (i) SPHINX trial (NCT03942211), an RCT to assess efficacy and safety of oral selexipag in SAPH, (ii) SAPPHIRE trial (NCT03814317), an open-label study with inhaled treprostinil for stage 4 pulmonary sarcoidosis with pulmonary hypertension, and (iii) an open-label study to assess the safety and efficacy of increasing doses of pulsed, inhaled nitric oxide (NO) in subjects with PH associated with pulmonary fibrosis or sarcoidosis on long term oxygen therapy followed by long term extension study (NCT03727451). It is also noteworthy that attention has been paid to the potential anti-inflammatory and anti-fibrotic effects of vasodilators [91][92][93][94]. Inhaled treprostinil improved FVC %pred and lowered the risk of clinical worsening and exacerbation of ILDs underlying PH in the INCREASE study [92].…”

“…Inhaled treprostinil improved FVC %pred and lowered the risk of clinical worsening and exacerbation of ILDs underlying PH in the INCREASE study [92]. Treatment with PH-targeted medications prevented FVC decline in patients with SAPH evaluated for LTx [93]. On the other hand, a prospective 12-month phase 2 RCT found no evidence for the efficacy of bosentan as an anti-fibrotic treatment for steroid-resistant pulmonary sarcoidosis [94].…”

“…Off-label uses of pulmonary vasodilators may be considered for symptomatic patients on a case-by-case basis [1,10]. They may be also useful in patients referred for LTx, potentially decreasing mortality while waiting on the list [93].…”