Dataset Information

The impact of comorbidities on selexipag treatment effect in patients with pulmonary arterial hypertension: insights from the GRIPHON study.

ABSTRACT:

Aims

The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing and there are limited data on response to PAH-targeted therapies in this population. These post hoc analyses explored the effect of selexipag in PAH patients with cardiovascular comorbidities in the GRIPHON study.

Methods and results

Randomized patients (n = 1156) were classified using three methods: (i) by subgroups defined according to previously published comorbidity count and restrictive haemodynamic criteria: Subgroup A (<3 comorbidities and haemodynamic criteria met; n = 962) and Subgroup B (≥3 comorbidities and/or haemodynamic criteria not met; n = 144); comorbidities included body mass index ≥30 kg/m² , essential hypertension, diabetes, history of coronary artery disease; (ii) by number of comorbidities, with addition of atrial fibrillation (0, 1, 2, 3, 4, or 5); (iii) by presence of individual comorbidities. Selexipag to placebo hazard ratios (HR) and 95% confidence intervals (CI) for morbidity/mortality (primary composite endpoint) were estimated using Cox regression adjusting selexipag effect for baseline covariates. Approximately half of the patients in GRIPHON (n = 584; 50.5%) had comorbidities. Selexipag reduced the risk of a morbidity/mortality event compared with placebo in both Subgroup A (HR 0.66, 95% CI 0.53, 0.82) and Subgroup B (HR 0.50, 95% CI 0.26, 0.96), with no evidence of an inconsistent treatment effect between subgroups (interaction p = 0.432). Consistent results were observed in analyses by number and by specific type of comorbidity.

Conclusion

Selexipag reduces the risk of a morbidity/mortality event vs. placebo irrespective of patient comorbidity status, suggesting that comorbidity status does not influence the treatment effect of selexipag.

SUBMITTER: Rosenkranz S

PROVIDER: S-EPMC9298818 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

The impact of comorbidities on selexipag treatment effect in patients with pulmonary arterial hypertension: insights from the GRIPHON study.

Rosenkranz Stephan S Channick Richard R Chin Kelly M KM Jenner Bartosz B Gaine Sean S Galiè Nazzareno N Ghofrani Hossein-Ardeschir HA Hoeper Marius M MM McLaughlin Vallerie V VV Du Roure Camille C Rubin Lewis J LJ Sitbon Olivier O Tapson Victor V Lang Irene M IM

European journal of heart failure 20211121 1

<h4>Aims</h4>The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing and there are limited data on response to PAH-targeted therapies in this population. These post hoc analyses explored the effect of selexipag in PAH patients with cardiovascular comorbidities in the GRIPHON study.<h4>Methods and results</h4>Randomized patients (n = 1156) were classified using three methods: (i) by subgroups defined according to previously published comorbidity count and res ...[more]

PMID: 34806261

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Project description:IntroductionPatients with connective tissue disorders (CTD) and pulmonary arterial hypertension (PAH) have a poorer prognosis than those with other PAH etiologies. This study assessed the impact of CTD on healthcare outcomes among PAH patients with and without CTD comorbidities that were treated with oral selexipag.MethodsThe study utilized Optum's de-identified Clinformatics® Data Mart Database (2007-2021) from January 1, 2014 to June 30, 2019, and identified patients with PAH without CTD and PAH with CTD treated with oral selexipag. Patients had ≥ 12-month baseline period with no requirement for a minimum follow-up period. Patients were followed until any of the following events: discontinuation of oral selexipag, or health plan disenrollment, or death, or presence of a diagnosis claim for CTEPH, or study end date, whichever occurred first. PAH-related hospitalizations, PAH disease progression, and healthcare utilizations and costs were assessed in the follow-up period. The Cox proportional hazards model was used to evaluate the time to hospitalization and generalized linear models were used to examine healthcare costs and utilization between the two cohorts.ResultsIn the analysis, 237 PAH without CTD, and 80 PAH patients with CTD comorbidities prescribed oral selexipag were included. The PAH without CTD comorbidities cohort was older (65 vs. 63 years old), had proportionately less females (72 vs. 83%), and higher comorbidity burden than PAH with CTD comorbidities (mean CCI index 3 vs. 2). After adjusting for potential confounders, the risk for PAH-related hospitalization (hazard ratio (HR) 1.13, p value 0.641), all-cause hospitalization (HR 1.09, p value: 0.765), and PAH disease progression (HR 1.14, p value 0.522) between the two cohorts were similar. After adjusting for baseline demographic and clinical characteristics, PAH with CTD comorbidities incurred higher total mean all-cause PAH-related medical care costs compared to PAH without CTD comorbidities.ConclusionsIn this real-world study, the risk of hospitalization and PAH disease progression were similar between the two cohorts who received oral selexipag. The results from this study corroborate findings of the GRIPHON post hoc analysis of PAH-associated CTD patients and support oral selexipag use in PAH-CTD patients.

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.

Dataset Information

The impact of comorbidities on selexipag treatment effect in patients with pulmonary arterial hypertension: insights from the GRIPHON study.

Aims

Methods and results

Conclusion

Publications

The impact of comorbidities on selexipag treatment effect in patients with pulmonary arterial hypertension: insights from the GRIPHON study.

Similar Datasets

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