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Prospective clinical assessment of patients with pulmonary arterial hypertension switched from bosentan to macitentan (POTENT).

ABSTRACT: Even though pulmonary arterial hypertension (PAH) remains an incurable disease, the combination of PAH-specific therapies allowed evolving from symptom-based strategies to others aiming to move patients to low-risk conditions. Endothelin-1 (ET-1) receptor antagonists emerged as specific-PAH drugs that can be used in combination with other specific therapies. This work aimed to perform a prospective clinical assessment of patients with PAH that switched from bosentan to macitentan (POTENT), due to inadequate response. POTENT is a prospective, open-label, single-arm, uncontrolled study including PAH patients from our ongoing SAUDIPH registry. It enrolled 50 PAH patients divided as follows: idiopathic/heritable pulmonary arterial hypertension (I/HPAH); n = 24; PAH associated with congenital heart disease, n = 19; PAH associated with connective tissue diseases, n = 5; and pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH), n = 2. At baseline, most patients were in World Health Organization Functional Class (WHO FC) II/III (52.0%). After switching to macitentan, patients were more likely to be in WHO FC I/II (78%) and 22% of the overall cohort moved to a lower risk condition, with three low risk stratification parameters. Mean 6-min walking distance increased about 34 m after 12 months, with a significant mean change over time (12.63 ± 11.69 at month 3 vs. 40.75 ± 12.57 at month 12, p = 0.002). Most haemodynamic parameters decreased over time, with corresponding negative mean changes (p < 0.001). The safety of macitentan was confirmed by the absence of anaemia and liver injury; clinical worsening was observed only in a small group of patients. In general, macitentan might be a valid alternative to bosentan in PAH stable patients on combination therapy with insufficient clinical response, and presenting intermediate and high-risk parameters. We anticipate that studying this strategy in PAH subgroups would further clarify its potential and limitations.

SUBMITTER: Aldalaan AM

PROVIDER: S-EPMC9063971 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Prospective clinical assessment of patients with pulmonary arterial hypertension switched from bosentan to macitentan (POTENT).

Aldalaan Abdullah M AM Saleemi Sarfraz A SA Weheba Ihab I Abdelsayed Abeer A Aleid Maha M MM Alzubi Fatima F Zaytoun Hamdeia H Alharbi Nadeen N

Pulmonary circulation 20220401 2

Even though pulmonary arterial hypertension (PAH) remains an incurable disease, the combination of PAH-specific therapies allowed evolving from symptom-based strategies to others aiming to move patients to low-risk conditions. Endothelin-1 (ET-1) receptor antagonists emerged as specific-PAH drugs that can be used in combination with other specific therapies. This work aimed to perform a prospective clinical assessment of patients with PAH that switched from bosentan to macitentan (POTENT), due t ...[more]

PMID: 35514768

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Project description:BackgroundConnective tissue disease (CTD) is the second most common cause of the pulmonary arterial hypertension (PAH). Currently, clinical data concerning CTD-PAH is scarce. Our study aimed to assess the efficacy and safety of macitentan in the treatment of CTD-PAH.MethodsIn this retrospective study, patients diagnosed with CTD-PAH at The First Affiliated Hospital of Soochow University from April 2020 to November 2021 were included. Of the patients, 9 were switched to macitentan monotherapy whereas 23 received initial combination therapy. The mean follow-up time was 24 weeks. Six-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography parameters before and after medication were assessed. Adverse reactions were also recorded and compared.ResultsAfter 24 weeks of treatment, 6MWD, NT-proBNP, systolic pulmonary artery pressure (sPAP) estimated by ultrasound, tricuspid regurgitation pressure gradient (TRPG) and tricuspid annular plane systolic excursion (TAPSE) in the macitentan monotherapy group revealed significant differences (Z=-2.67, Z=-2.67, t=6.20, t=5.60, t=-3.04, P<0.05). There were no statistically significant differences in right ventricular diameter (RVD), right atrial diameter (RAD), ascending aortic root inner diameter (AAO) and left ventricular end-diastolic diameter (LVEDd) (P>0.05). After 24 weeks of medication, the number of patients with WHO-FC grade III/IV symptoms decreased from 6 to 3, 1 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 2, 2 to 4 respectively(P<0.05). After 24 weeks of treatment, 6MWD, NT-proBNP, LVEDd, sPAP and TRPG in the macitentan combined with sildenafil treatment group revealed statistically significant differences (Z=-4.11, Z=-3.74, Z=-3.83, t=6.88, t=6.54, P<0.001). Significant differences in RVD, RAD, and TAPSE were found (t=3.46, t=3.69, t=-3.12, P<0.05). There were no statistically significant variances in AAO between the groups (P>0.05). The number of patients with WHO-FC grade III/IV symptoms decreased from 16 to 8, 5 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 1, 2 to 14 respectively (P<0.001). There were no statistically significant differences before and after treatment in 6MWD, NT-proBNP, RVD, RAD, AAO, LVEDd, sPAP, TRPG and TAPSE between the two groups (P>0.05). There were no statistically significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr) and hemoglobin (Hb) between 0 and 24 weeks (P>0.05).ConclusionsExercise tolerance and cardiac function in patients with CTD-PAH were significantly improved after treatment with macitentan, which was well tolerated. Therefore, macitentan may be an effective and safe targeted drug for CTD-PAH.

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.

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Prospective clinical assessment of patients with pulmonary arterial hypertension switched from bosentan to macitentan (POTENT).

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Prospective clinical assessment of patients with pulmonary arterial hypertension switched from bosentan to macitentan (POTENT).

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