Chronic thromboembolic pulmonary hypertension (CTEPH), a rare pulmonary vascular disease, is often misdiagnosed due to nonspecific symptoms. The objective of the study was to develop, refine and validate a case ascertainment algorithm to identify CTEPH patients within the French exhaustive hospital discharge database (PMSI), and to use it to estimate the annual number of hospitalized patients with CTEPH in France in 2015, as a proxy for disease prevalence. As ICD-10 coding specifically for CTEPH was not available at the time of the study, a case ascertainment algorithm was developed in close collaboration with an expert committee, using a two-step process (refinement and validation), based on matched data from PMSI and hospital medical records from 2 centres. The best-performing algorithm (specificity 95%, sensitivity 70%) consisted of ≥1 pulmonary hypertension (PH) diagnosis during 2015 and any of the following criteria over 2009-2015: (i) CTEPH interventional procedure, (ii) admission for PH and pulmonary embolism (PE), (iii) PE followed by hospitalization in competence centre then in reference centre, (iv) history of PE and right heart catheterization. Patients with conditions suggestive of pulmonary arterial hypertension were excluded. A total of 3,138 patients hospitalized for CTEPH was estimated for 2015 (47 cases/million, range 43 to 50 cases/million). Assuming that patients are hospitalized at least once a year, the present study provides an estimate of the minimal prevalence of CTEPH and confirms the heavy burden of this disease.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of unresolved organised pulmonary emboli/thrombi obstructing the major pulmonary arteries. The aim of this study was to estimate the incidence and risk factors of CTEPH in a cohort with first venous thromboembolism (VTE). This was a population-based cohort study of patients with first VTE and no active cancer in England between 2001 and 2012. CTEPH was assessed using a rigorous case-ascertainment algorithm. Risk factors for CTEPH were studied using a nested case-control approach by matching CTEPH cases to VTE patients without CTEPH. Adjusted odds ratios (OR) of comorbidities were estimated from conditional logistic regression. During 81,413 person-years of follow-up among 23,329 patients with first VTE (mean follow-up 3.5 years; maximum 11.0 years) 283 patients were diagnosed with CTEPH (incidence rate 3.5 per 1000 person-years); cumulative incidence was 1.3% and 3.3% at 2 and 10 years after pulmonary embolism, and 0.3% and 1.3% following deep vein thrombosis (DVT), respectively. Risk factors for CTEPH included age over 70, OR 2.04 (95% CI 1.23 to 3.38), female gender, 1.44 (1.06 to 1.94), pulmonary embolism at first VTE, 3.11 (2.23 to 4.35), subsequent pulmonary embolism and DVT, 3.17 (2.02 to 4.96) and 2.46 (1.34 to 4.51) respectively, chronic obstructive pulmonary disease 3.17 (2.13 to 4.73), heart failure 2.52 (1.76 to 3.63) and atrial fibrillation, 2.42 (1.71 to 3.42). CTEPH develops most commonly after pulmonary embolism and less frequently after DVT. Awareness of risk factors may increase referrals to specialised centres for confirmation of CTEPH and initiation of specific treatment.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare pulmonary vascular disease for which epidemiological data are limited and no ICD-10 diagnosis code was available in the French national hospital discharge database (PMSI). The objective was to develop and validate an algorithm identifying patients with CTEPH within the PMSI, and to estimate the number of patients hospitalized for CTEPH in France in 2015. An expert committee designed a first algorithm combining diagnoses and procedures codes, based on their CTEPH care pathway knowledge, published algorithms and analysis of coding of confirmed CTEPH cases in the PMSI. Then, the algorithm underwent a stepwise refinement, based on matched data from PMSI and patient records with clinically validated CTEPH diagnosis, provided by a first participating expert centre (Paris). Lastly, performance indicators of the final algorithm were measured using patient records from the second participating expert centre (Lyon). The selected algorithm consisted of ≥1 secondary pulmonary hypertension (PH) diagnosis over 2015 and any of the following criteria over a previous 6-year period: (i) CTEPH-specific interventional procedure, (ii) admission for PH and pulmonary embolism (PE), (iii) PE followed by hospitalization in competence centre then in reference centre, (iv) history of PE and right heart catheterization. Patients with conditions suggestive of pulmonary arterial hypertension were excluded. The final algorithm had 95% specificity, 70% sensitivity, 99% negative predictive value, and 41% positive predictive value. When applied to all PMSI and after correction based on algorithm performance, 3,138 patients hospitalized for CTEPH were estimated in 2015 (47 cases/million). This first algorithm allowing the identification of CTEPH cases into the PMSI database provides an estimate of the prevalence of CTEPH in France, notably useful for budget impact evaluations.

Background: CTEPH, a rare pulmonary vascular disease, is often misdiagnosed due to nonspecific symptoms. Orphanet estimates the prevalence as 30 cases/million; however a recent review suggested 45 cases/million in France [Gall 2017]. We aimed at estimating the frequency of CTEPH using PMSI. Aims: To estimate the number of patients hospitalised for CTEPH in France in 2015. Methods: As ICD-10 coding for pulmonary hypertension (PH) does not uniquely document CTEPH, a case ascertainment algorithm to identify CTEPH hospitalizations was developed in close collaboration with an expert committee, using a two-step process (refinement and validation), based on matched data from PMSI and hospital medical records from 2 competence centres (Paris, Lyon). Results: The best-performing algorithm (specificity 95%, sensitivity 70%, negative predictive value 99%, positive predictive value 41%) consisted of ≥1 PH diagnosis during one year (2015) and any of the following criteria over a 6-year period (2009-2015): (i) CTEPH surgery (ii) admission for PH and pulmonary embolism (PE) (iii) PE followed by hospitalisation in competence centre then in reference centre (iv) history of PE and right heart catheterisation. Patients with conditions suggestive of pulmonary arterial hypertension were excluded. When applied to all PMSI, a total of 3,138 patients hospitalised for CTEPH was estimated in 2015 (47 cases/million). Conclusions: Our method provides an estimate of over 3,000 hospitalised patients with CTEPH in France in 2015 (~67 million inhabitants). Assuming patients are hospitalized at least once a year, this may represent the disease prevalence. This study confirms the heavy burden of CTEPH.

This study aimed to validate an algorithm developed to identify chronic thromboembolic pulmonary hypertension (CTEPH) among patients with a history of pulmonary embolism. Validation was halted because too few patients had gold-standard evidence of CTEPH in the administrative claims/electronic health records database, suggesting that CTEPH is underdiagnosed.

Background Group 3 pulmonary hypertension (PH) encompasses PH owing to lung diseases and/or hypoxia. Treatment patterns, healthcare resource use, and economic burden to US payers of Group 3 PH patients were assessed. Methods This retrospective observational study extracted data from July 1, 2010 to June 30, 2013 from two Truven Health Analytics MarketScan databases. Adult Group 3 PH patients were identified based on claims for PH (ICD-9-CM 416.0/416.8), a related lung disease, and an echocardiogram or right heart catheterization (RHC). The index date was the date of the first PH claim; data were collected for 12 months pre- and post-index. A difference-in-difference approach using generalized estimating equations was done to account for baseline differences. Results Group 3 PH patients ( n = 2,236) were matched 1:1 to controls on lung disease. PH patients had higher all-cause resource utilization and annual healthcare costs ($44,732 vs. $7,051) than controls. Costs were driven by inpatient admissions (35.4% of total costs), prescriptions (33.0%), and outpatient care (26.5%). Respiratory-related costs accounted for 11.4% of post-index annual costs for PH patients. PH diagnosis was not confirmed in the majority of PH patients (<7% RHC use) but nevertheless, 22% of PH patients post-index had claims for drugs approved for the treatment of pulmonary arterial hypertension (PAH). Conclusions Group 3 PH poses a significant clinical and economic burden. Given the low use of RHC and the prevalence of PAH-indicated prescriptions that are not currently approved for Group 3 PH, this study suggests some Group 3 PH patients may not be receiving guideline-recommended treatment.

Few controlled clinical trials exist to support oral combination therapy in pulmonary arterial hypertension (PAH).

BACKGROUND: Pulmonary hypertension and chronic thromboembolic pulmonary hypertension may develop after a pulmonary embolism event. A ventilation-perfusion scan is recommended as a first-line modality for suspected chronic thromboembolic pulmonary hypertension. In this study, we determined the prevalence of pulmonary hypertension following incident pulmonary embolism and the disease-monitoring patterns in this population.METHODS: We conducted a retrospective claims database analysis of incident pulmonary embolism cases (July 1, 2010 to September 30, 2011) and extracted data for 1 year prior to and 2 years after the incident pulmonary embolism event. Data were analyzed for diagnoses and symptoms related to pulmonary hypertension, claims consistent with other heart or lung diseases, diagnostic imaging tests, and time to first diagnostic imaging test post pulmonary embolism.RESULTS: Of the 7068 incident pulmonary embolism patients that met eligibility criteria, 87% had a claim for a pulmonary hypertension-related symptom and 7.6% had a claim for pulmonary hypertension during follow-up. Only 55% of all pulmonary embolism patients had diagnostic procedural claim(s) post pulmonary embolism: echocardiogram, 47%; computed tomographic angiography, 20%; ventilation-perfusion scan, 6%; and right heart catheterization or pulmonary angiography, <1%. The mean time from pulmonary embolism diagnosis to first screening test was 131 days.CONCLUSIONS: Despite exhibiting pulmonary hypertension-related symptoms, many pulmonary embolism patients did not undergo imaging tests that could diagnose pulmonary hypertension or chronic thromboembolic pulmonary hypertension. This study suggests that physician education about the risk of pulmonary hypertension and chronic thromboembolic pulmonary hypertension after pulmonary embolism may need to be improved. (C) 2016 Elsevier Inc. All rights reserved.

Pulmonary hypertension (PH) is classified into 5 groups. Group 3-PH is PH associated with lung diseases, such as chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), or those associated with sleep-related breathing disorders. We estimated the burden of Group 3 PH patients to US payers. A 1:1 case-control study design using a large health insurance claims database was employed. Group 3-PH patients were identified using the following inclusion criteria: ≥2 medical claims for PH during July 1 2011 through June 30 2012; at least one procedural claim for echocardiogram or right heart catheterization, and at least one medical claim for COPD, ILD, breathing sleep disorders, alveolar hypoventilation disorder, chronic exposure to high altitude, or developmental lung diseases. Patients were excluded if they had a medical claim for left heart disease, pulmonary embolism, hematologic disorders, systemic disorders, metabolic disorders or other categories as described in the 2013 classification of PH anytime during the study period. Controls were selected based on a propensity score methodology ensuring exactly the same baseline lung disease distribution between the 2 groups and no medical claim for PH across the entire study period. A total of 2,236 cases met study criteria. On average, cases were significantly (p<0.01) younger (67 vs. 71), more females (64% vs 58%) and higher comorbid burden (2.8 vs 2.09) compared to controls. After adjusting for all baseline characteristics cases had significantly higher (p<0.001) inpatient admissions (5.0 vs 2.4), physician office visits (16.5 vs 12.5), emergency room visits (0.7 vs 0.5), pharmacy claims (67 vs 54). This translated into higher expenditures among cases ($42,914) vs controls ($16,745) at per patient per year level. Using health plan data this study showed that Group 3-PH poses a significant economic burden to payers.

Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disease affecting overall health status and quality of life. Riociguat has demonstrated a consistent benefit as a treatment for PAH within one year of treatment. This analysis sought to assess the long-term impact of riociguat on patient-reported health status over the 2-year PATENT-2 study. In the PATENT-1 study, PAH patients were randomized to receive placebo, riociguat individual dose titration up to 2.5 mg TID (three times a day), or riociguat fixed dose titration at 1.5mg TID. PATENT-2 is an open-label extension phase where all patients received riociguat up to 2.5mg TID. Patient reported health status in PATENT-1 (baseline and week 12) and PATENT-2 (long term extension (LTE) week 12, and LTE months 6, 9, 12 and 24) was assessed using the EQ-5D. Responder analyses were performed to evaluate EQ-5D scores in the context of clinical outcomes (6-minute walk distance (6MWD) and WHO functional class). EQ-5D utility scores and response distributions were analysed. In the total sample patients demonstrated an increase in mean EQ-5D utility scores between baseline (mean 0.682, n=392) and month 24 (mean 0.733, n=221); a trend mirrored by improvement in EQ-5D VAS score from baseline (mean 62.5, n=388) to month 24 (mean 72.3, n=219). At month 24 a general improvement in all EQ-5D domains, except self-care, was observed regardless of participants’ previous treatment arm. Responder analyses indicated that patients with greater improvement in 6MWD (>40m) at week 12 had higher mean scores than those with less improvement (<40m) at all time-points throughout the two year follow-up. Furthermore, patients with better functional capacity according to WHO classification (class I/II) had higher EQ-5D utility scores than those with worse capacity (class III/IV). Results demonstrate the long-term positive impact of riociguat on PAH patients’ reported health status.

**Background:** Pulmonary arterial hypertension (PAH) is a disease characterized by dyspnea, fatigue, chest pain and syncope. As there is no known cure for PAH, the goal of treatment is to control symptoms and slow disease progression. Sildenafil, a phosphodiesterase-5 inhibitor, has been indicated to improve exercise capacity in PAH in both the United States and the European Union since 2005; since 2009, it also has been indicated in the United States to delay clinical worsening. Patterns of sildenafil use in PAH patients have not been reported. **Objectives:** To describe patterns of treatment with sildenafil among commercially insured patients in the United States with PAH. **Methods:** Using a large U.S. healthcare claims database, we identified all patients with evidence of PAH (International Classification of Disease, 9th Revision, Clinical Modification [ICD-9-CM] diagnosis codes 416.0, 416.8) and receipt of sildenafil between January 1, 2005 and September 30, 2008. The date of each patient’s earliest pharmacy claim for sildenafil was designated as his or her “index date”; patients with <6 months of data prior to this date were excluded. Post-index use of sildenafil was then examined in terms of the numbers of pharmacy claims and therapy-days, the medication possession ratio (MPR), and the incidence of therapy switching. **Results:** We identified a total of 855 PAH patients who began sildenafil therapy and met all other entry criteria. Mean (standard deviation [SD]) follow-up was 423.4 (313.0) days. Over this period, these patients averaged 7.1 (6.8) (median, 5) pharmacy dispensings for sildenafil, representing 273.4 (254.8) therapy-days (median, 180). Mean MPR was 71% (median, 83%). Fourteen percent of sildenafil patients switched to another agent during follow-up. **Conclusions:** In “real-world” clinical practice, many PAH patients beginning treatment with sildenafil remain on therapy for extended periods and are relatively compliant with treatment.

BACKGROUND: Elevated serum uric acid is detected in pulmonary arterial hypertension (PAR) and is associated with poor patient outcomes. High serum uric acid is an independent risk factor for cardiovascular disease and renal impairment. We analyzed the effects of endothelin receptor antagonism on serum uric acid in PAR patients participating in the Sitaxentan to Relieve Impaired Exercise (STRIDE)-2/2X trial, and the impact of uric acid on 6-minute walk distance (6MWD), time to clinical worsening (TtCW) and survival.METHODS: In the 18-week, double-blind, placebo-controlled STRIDE-2 trial, 246 PAH patients were randomized and received matched placebo, sitaxentan 50 or 100 mg orally once daily, or open-label bosentan 125 mg twice daily. STRIDE-2X was a 1-year, open-label extension of STRIDE-2.RESULTS: Baseline serum uric acid was similar between groups. Increased serum uric acid was a significant risk factor for 1-year mortality and TtCW. Compared with placebo, sitaxentan 50 and 100 mg and bosentan all reduced serum uric acid (p < 0.05). Reduced serum uric acid correlated with increased 6MWD (p = 0.0037).CONCLUSIONS: Endothelin receptor antagonism reduces serum uric acid in PAR patients, and this reduction is associated with improved survival and longer TtCW. Further prospective studies are needed to investigate the pathogenic role of serum uric acid in PAH and its prognostic potential. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.