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Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report.

ABSTRACT: Background?:Selexipag is an oral selective prostacyclin IP receptor agonist approved in patients with low- and intermediate-risk pulmonary hypertension (PH); evidence in patients at high risk is lacking. Case summary?:A 42-year-old woman with worsening dyspnoea (World Health Organization functional class III-IV) and suspected PH at echocardiographic examination was evaluated in our Pulmonary Hypertension Centre. Right heart catheterization showed pre-capillary PH with reduced cardiac index and increased pulmonary vascular resistance. High-resolution computed tomography excluded parenchymal lung disease and ventilation/perfusion (V/Q) lung scan was negative for mismatched perfusion defects so the conclusive diagnosis was high-risk idiopathic pulmonary arterial hypertension (PAH). The patient refused an initial combination therapy including a parenteral prostacyclin analogue (PCA) in accordance with the ESC/ERS guidelines, so an off-label triple oral combination therapy including a phosphodiesterase-5 inhibitor, an endothelin receptor antagonist, and selexipag was started. At 3- and 6-month follow-up we found a clinical and haemodynamic improvement, so the patient was reclassified as low risk. Her clinical condition is currently stable. Discussion?:Despite the benefit of parenteral PCAs in high-risk PAH, low adherence to treatment may be explained by adverse side effects related to the intravenous route of administration. Given the potential effect seen in our patient, upfront triple oral combination therapy in PAH high-risk patients should be further evaluated in a controlled clinical trial.

SUBMITTER: Rossi S

PROVIDER: S-EPMC7649462 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report.

Rossi Serena S Pietrangelo Carla C Pierdomenico Sante Donato SD Giuliani Livio L

European heart journal. Case reports 20200830 5

<h4>Background</h4>Selexipag is an oral selective prostacyclin IP receptor agonist approved in patients with low- and intermediate-risk pulmonary hypertension (PH); evidence in patients at high risk is lacking.<h4>Case summary</h4>A 42-year-old woman with worsening dyspnoea (World Health Organization functional class III-IV) and suspected PH at echocardiographic examination was evaluated in our Pulmonary Hypertension Centre. Right heart catheterization showed pre-capillary PH with reduced cardia ...[more]

PMID: 33204960

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Project description:BackgroundThe evidence regarding triple oral combination therapy for patients with pulmonary arterial hypertension (PAH) is scarce. This study was performed to investigate the effectiveness and safety of triple oral combination therapy with macitentan, riociguat, and selexipag.MethodsAmong consecutive patients with PAH who were referred to our hospital from 2009 to 2020, those who underwent triple oral combination therapy using macitentan, riociguat, and selexipag were retrospectively analyzed. Hemodynamic and echocardiographic assessments and Kaplan-Meier analyses of all-cause death and initiation of prostacyclin infusion were conducted.ResultsTwenty-six patients underwent this combination therapy. These patients were predominantly female (73.1%) with a median age of 38 years at baseline and nine patients were taking some PAH medications at baseline. The median time from initiation of the first PAH drug to the third PAH drug in treatment naïve patients was 24 days (interquartile range, 12-47 days). Four patients (15.0%) discontinued taking any of the three vasodilators because of adverse events, and 17 patients (65.4%) reached the maximum dose of all three drugs. The mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output improved by 29%, 65%, and 82%, respectively (median observation period: 441 days) and similar improvements were observed in treatment-naïve patients at baseline. The survival rate and prostacyclin infusion-free rate since administration of all three vasodilators was 93.3% and 74.6% at 3 years, respectively. When patients were divided by risk stratification, the prostacyclin-free rate at 3 years was 92.9% in low-/intermediate-risk patients and 55.0% in high-risk patients.ConclusionTriple oral combination therapy with macitentan, riociguat, and selexipag sufficiently improved clinical parameters and was well tolerated in patients with PAH. This combination could be a particularly promising strategy in patients with low/intermediate risk and possibly even in half of patients with high risk. Further studies are needed to validate these findings.The reviews of this paper are available via the supplemental material section.

Project description:Aim Selexipag is an oral selective prostacyclin receptor agonist approved for treatment of patients with pulmonary arterial hypertension (PAH). In the present study, we aim to assess the safety and efficacy of selexipag in triple combination therapy with endothelial receptor antagonists (ERAs) and PDE5is for Chinese PAH patients. Methods and results A single center retrospective study was performed on group 1 PAH patients (n = 68) initiating triple combination therapy with selexipag from 1 February 2020 to 31 August 2021 in Qilu Hospital of Shandong University (Shandong, China). Adolescents, children, and PAH patients with unrepaired congenital heart disease were excluded. The French pulmonary hypertension network (FPHN) non-invasive risk assessment, echocardiogram parameters, and clinical data, including tolerability, safety, and death/hospitalization events associated with PAH, were collected. Of the 68 patients, 31 (45.6%) patients had tolerable side effects while only a single patient discontinued selexipag due to severe diarrhea. In the analysis of the efficacy set of 62 patients, the median selexipag treatment time from selexipag initiation to last risk assessment was 27 (21, 33) weeks. Compared to baseline parameters, the percentage of WHO FC III/IV decreased from 77.4% (48) to 24.2% (15) (p = 0.000), median 6-min walk distance (6MWD) increased 82 m [from 398 (318, 450) to 480 (420, 506) m; p = 0.000], and NT-proBNP levels decreased from 1,216 (329, 2,159) to 455 (134, 1,678) pg/mL (p = 0.007). Patients who improved to three low-risk criteria increased from 9.7 to 38.7%. Right ventricular diameter (RV) diameter also decreased and was accompanied by an improved tricuspid annular plane systolic excursion (TAPSE). Patients transitioning from subcutaneous treprostinil to selexipag continued to show improvements in WHO FC, 6MWD (404 ± 94 vs. 383 ± 127 m) and NT-proBNP levels (2,319 ± 2,448 vs. 2,987 ± 3,770 pg/mL). Finally, the 1-year event free survival rate was 96.7% for patients initiating the triple combination therapy within 3 years of PAH diagnosis. Conclusion Triple combination therapy with selexipag was safe and effective in Chinese PAH patients, which was confirmed by acceptable tolerability, and improved exercise capacity, right heart function, risk assessment, and prognosis.

Project description:Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous vascular involvement according to a pre-specified, semi-quantitative grading scheme, which categorizes the intensity of venous remodeling in three groups of incremental severity: venous hypertensive (VH) grade 0 = characterized by an absence of venous vascular remodeling; VH grade 1 = defined by a dominance of either arterialization or intimal fibrosis; and VH grade 2 = a substantial composite of arterialization and intimal fibrosis. Patients were grouped according to clinical and hemodynamic characteristics in three groups: COPD non-PH, COPD-PH, and IPAH, respectively. Histological specimens were examined by a cardiovascular pathologist blinded to clinical and hemodynamic data. Pathological alterations of pulmonary veins were present in all hemodynamic groups, with the following incidences of VH grade 0/1/2: 34/66/0% in COPD non-PH; 19/71/10% in COPD-PH; and 11/61/28% in IPAH. In COPD, explorative correlation analysis of venous remodeling suggested a modest positive correlation with systolic and mean pulmonary artery pressure ( P = 0.032, respectively) and an inverse modest correlation with diffusion capacity for carbon monoxide ( P = 0.027). In addition, venous remodeling correlated positively with the degree of arterial remodeling ( P = 0.014). In COPD-PH and IPAH, advanced forms of pulmonary venous remodeling are present, emphasizing that the disease is not exclusively restricted to arterial lesions. In addition, venous remodeling may be related to the hemodynamic severity, but more rigorous analysis is required to clearly define potential relationships.

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Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report.

Publications

Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report.

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