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Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil.

ABSTRACT: INTRODUCTION:Anticoagulation is a common treatment modality in patients with pulmonary arterial hypertension (PAH). Further studies are needed to appropriately assess the risk/benefit ratio of anticoagulation, particularly in PAH patients receiving PAH-specific therapies. AIMS:We use observational long-term data on PAH patients treated with subcutaneous (SQ) treprostinil from a large open-label study. Patients were followed for up to 4 years. The use of warfarin and bleeding events were recorded. RESULTS:At total of 860 patients (age [mean±SD] 46±15 years, 76% female, 83% Caucasian, 49% idiopathic PAH, and 76% New York Heart Association [NYHA] functional class III) were included. All patients received SQ treprostinil (15% also other pulmonary hypertension [PH]-therapies) and 590 (69%) received warfarin during the study. The proportions of women, African American, and idiopathic pulmonary hypertension (IPAH) patients were higher in the group receiving warfarin. A higher proportion of patients with congenital heart disease and portopulmonary hypertension did not receive warfarin. There were no differences in unadjusted long-term survival between PAH patients receiving warfarin or not (log-rank test, P value=.69), even when only considering idiopathic PAH (P=.32). In addition, no difference was found in adjusted long-term survival both in PAH (P=.84) and idiopathic PAH patients (P=.44) based on the use of warfarin. Furthermore, no survival difference based on the use of warfarin were noted between propensity score-matched PAH patients (P=.37). CONCLUSIONS:Long-term anticoagulation with warfarin was not associated with any significant effect on survival in PAH or idiopathic PAH patients treated with SQ treprostinil.

SUBMITTER: Ascha M

PROVIDER: S-EPMC5600501 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil.

Ascha Mona M Zhou Xuan X Rao Youlan Y Minai Omar A OA Tonelli Adriano R AR

Cardiovascular therapeutics 20171001 5

<h4>Introduction</h4>Anticoagulation is a common treatment modality in patients with pulmonary arterial hypertension (PAH). Further studies are needed to appropriately assess the risk/benefit ratio of anticoagulation, particularly in PAH patients receiving PAH-specific therapies.<h4>Aims</h4>We use observational long-term data on PAH patients treated with subcutaneous (SQ) treprostinil from a large open-label study. Patients were followed for up to 4 years. The use of warfarin and bleeding event ...[more]

PMID: 28643420

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Project description:Background and aimsTreprostinil is a prostacyclin analog used to treat pulmonary arterial hypertension. Dosing is empiric and based on tolerability. Adverse effects are common and can affect treatment persistence. Pharmacogenomic variants that may affect treprostinil metabolism and transport have not been well-characterized. We aimed to investigate the pharmacogenomic sources of variability in treatment persistence and dosing.MethodsPatients were prospectively recruited from an IRB approved biobank registry at a single pulmonary hypertension center. A cohort of patients who received oral treprostinil were screened for participation. Pharmacogenomic analysis was for variants in CYP2C8, CYP2C9, and ABCC4. A retrospective review was conducted for demographics, clinical status, dosing, and response. Fisher's exact test was used for categorical data and Kruskal-Wallis test or Wilcoxon rank sum were used for continuous data.ResultsA total of 15 patients received oral treprostinil and were consented. Their median age was 53 years, 73% were female, and 93% were White. The median total daily dose was 22.5 mg (13.5, 41) at last clinical observation. 40% of patients discontinued treatment with a majority due to adverse effects. Approximately 27% of patients had a loss-of-function variant in CYP2C8 (*1/*3 or *1/*4), whereas 47% of patients had a loss-of-function variant in CYP2C9 (*1/*2, *1/*3, or *2/*2). Minor allele frequencies for ABCC4 (rs1751034 and rs3742106) were 0.17 and 0.43, respectively. Survival analysis showed that increased CYP2C9 activity score was associated with decreased risk for treatment discontinuation [hazard ratio (HR): 0.13; 95% confidence interval (CI): 0.02, 0.91; p = 0.04]. Genetic variants were not significantly associated with dosing.ConclusionGenetic variants responsible for the metabolism and transport of oral treprostinil were common. Increased CYP2C9 activity score was associated with decreased risk for treatment discontinuation. However, dosing was not associated with genetic variants in metabolizing enzymes for treprostinil. Our findings suggest significant variability in treatment persistence to oral treprostinil, with pharmacogenomics being a potentially important contributor.The reviews of this paper are available via the supplemental material section.

Project description:BACKGROUND: Patient treatment satisfaction is likely to be a highly relevant outcome measure in pulmonary arterial hypertension (PAH), a condition for which the benefits of treatment must be weighed against frequent, undesirable side effects, inconvenience, and complications associated with therapy. In this study, we sought to evaluate the psychometric properties of a patient-reported treatment satisfaction measure and its relationship to quality of life (QoL) among patients transitioning from inhaled iloprost (iILO) to inhaled treprostinil (iTRE). METHODS: We studied treatment satisfaction among 66 subjects with PAH in a single-arm, open-label, multi-center trial of iTRE following transition from iILO. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM, version 1.4) administered to subjects immediately before and 12 weeks after transition of inhaled therapy. The TSQM is comprised of 4 domains: effectiveness, side effects, convenience, and global satisfaction. Scores range from 0 to 100 with higher scores indicating greater satisfaction. Six-minute walk distance (6MWD), functional class, adverse events, drug administration time, and PAH-specific QoL (CAMPHOR) were concurrently assessed. RESULTS: Domains of the TSQM demonstrated evidence of strong internal consistency at baseline and at 12 weeks (Cronbach ? = 0.88-0.93). Transition from iILO to iTRE was associated with an improvement in 3 of 4 TSQM domains: effectiveness (+20 ± 21, p < 0.0001), side effects (0 ± 22, p = 0.97), convenience (+39 ± 26, p < 0.0001), and global satisfaction (+20 ± 24, p = 0.0005). Change in effectiveness scores correlated with change in 6MWD (r = 0.43, p = 0.0004) and side effects scores at 12 weeks correlated inversely with number of severity-weighted treatment-emergent adverse events (r = -0.44, p = 0.0002). In multiple regression models adjusted for baseline characteristics, changes in effectiveness and convenience satisfaction scores were significantly associated with improvement in PAH-specific QoL (p = 0.002 and p = 0.01). CONCLUSIONS: The TSQM demonstrated acceptable performance characteristics in patients with PAH. Changes in treatment satisfaction resulting from transitioning from iILO to iTRE were associated with improvements in PAH-specific QoL.

Project description:To compare survival of patients with newly diagnosed pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) according to various clinical classifications with classifications of anatomical-pathophysiological systemic to pulmonary shunts in a single-center cohort.All prevalent cases of PAH-CHD with hemodynamic confirmation by cardiac catheterization in 1995-2015 were retrospectively reviewed. Patients who were younger than three months of age, or with single ventricle following surgery were excluded. Baseline characteristics and clinical outcomes were retrieved from the database. The survival analysis was performed at the end of 2016. Prognostic factors were identified using multivariate analysis.A total of 366 consecutive patients (24.5 ± 17.6 years of age, 40% male) with PAH-CHD were analyzed. Most had simple shunts (85 pre-tricuspid, 105 post-tricuspid, 102 combined shunts). Patients with pre-tricuspid shunts were significantly older at diagnosis in comparison to post-tricuspid, combined, and complex shunts. Clinical classifications identified patients as having Eisenmenger syndrome (ES, 26.8%), prevalent left to right shunt (66.7%), PAH with small defect (3%), or PAH following defect correction (3.5%). At follow-up (median = 5.9 years; 0.1-20.7 years), no statistically significant differences in survival rate were seen among the anatomical-pathophysiological shunts (p = 0.1). Conversely, the clinical classifications revealed that patients with PAH-small defect had inferior survival compared to patients with ES, PAH post-corrective surgery, or PAH with prevalent left to right shunt (p = 0.01). Significant mortality risks were functional class III, age < 10 years, PAH-small defect, elevated right atrial pressure > 15 mmHg, and baseline PVR > 8 WU•m.2.Patients with PAH-CHD had a modest long-term survival. Different anatomical-pathophysiological shunts affect the natural presentation, while clinical classifications indicate treatment strategies and survival. Contemporary therapy improves survival in deliberately selected patients.

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Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil.

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Impact on survival of warfarin in patients with pulmonary arterial hypertension receiving subcutaneous treprostinil.

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