scholarly journals Assessment of the REPLACE study composite endpoint in riociguat-treated patients in the PATENT study

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402097312
Author(s):  
Gérald Simonneau ◽  
Hossein-Ardeschir Ghofrani ◽  
Paul A. Corris ◽  
Stephan Rosenkranz ◽  
Ekkehard Grünig ◽  
...  
Keyword(s):  
Relative Risk ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Clinical Improvement ◽  
Composite Endpoint ◽  
World Health ◽  
Walking Distance ◽  
Pulmonary Arterial ◽  
Clinical Worsening

The goal of treatment in patients with pulmonary arterial hypertension is to achieve a low risk status, indicating a favorable long-term outcome. The REPLACE study investigated the efficacy of switching to riociguat in patients with pulmonary arterial hypertension and an insufficient response to phosphodiesterase-5 inhibitors. In this post hoc analysis, we applied the REPLACE composite endpoint of clinical improvement to the placebo-controlled PATENT-1 study of riociguat in pulmonary arterial hypertension and its long-term extension, PATENT-2. Clinical improvement was defined as ≥2 of the following in patients who completed the study without clinical worsening: ≥10% or ≥30 m improvement in 6-minute walking distance; World Health Organization functional class I or II; ≥30% decrease in N-terminal prohormone of brain natriuretic peptide. At PATENT-1 Week 12, patients treated with riociguat were more likely to achieve the composite endpoint vs. placebo ( P < 0.0001), with similar results in pretreated ( P = 0.0189) and treatment-naïve ( P < 0.0001) patients. Achievement of the composite endpoint at Week 12 was associated with a 45% reduction in relative risk of death and a 19% reduction in relative risk of clinical worsening in PATENT-2. Overall, these data suggest that use of the REPLACE composite endpoint in patients with pulmonary arterial hypertension is a valid assessment of response to treatment.

scholarly journals Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2)

2015 ◽  
Vol 45 (5) ◽  
pp. 1303-1313 ◽  
Author(s):  
Lewis J. Rubin ◽  
Nazzareno Galiè ◽  
Friedrich Grimminger ◽  
Ekkehard Grünig ◽  
Marc Humbert ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Primary Objective ◽  
Functional Class ◽  
World Health ◽  
Walking Distance ◽  
Open Label ◽  
Pulmonary Arterial

Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary arterial hypertension. In the 12-week PATENT-1 study, riociguat was well tolerated and improved several clinically relevant end-points in patients with pulmonary arterial hypertension who were treatment naïve or had been pretreated with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label extension evaluated the long-term safety and efficacy of riociguat.Eligible patients from the PATENT-1 study received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was to assess the safety and tolerability of riociguat; exploratory efficacy assessments included 6-min walking distance and World Health Organization (WHO) functional class.Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in PATENT-2 was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min walking distance and WHO functional class observed in PATENT-1 persisted for up to 1 year in PATENT-2. In the observed population at the 1-year time point, mean±sd 6-min walking distance had changed by 51±74 m and WHO functional class had improved in 33%, stabilised in 61% and worsened in 6% of the patients versus the PATENT-1 baseline.Long-term riociguat was well tolerated in patients with pulmonary arterial hypertension, and led to sustained improvements in exercise capacity and functional capacity for up to 1 year.

Single-center prognostic validation of the risk assessment of the 2015 ESC/ERS guidelines in patients with pulmonary arterial hypertension in Japan

2020 ◽  
Vol 98 (9) ◽  
pp. 653-658 ◽  
Author(s):  
Ryo Imai ◽  
Shiro Adachi ◽  
Masahiro Yoshida ◽  
Shigetake Shimokata ◽  
Yoshihisa Nakano ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Risk Group ◽  
Low Risk ◽  
World Health ◽  
Right Atrial ◽  
Walking Distance ◽  
Pulmonary Arterial

The 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension include a multidimensional risk assessment for patients with pulmonary arterial hypertension (PAH). However, prognostic validations of this risk assessment are limited, especially outside Europe. Here, we validated the risk assessment strategy in PAH patients in our institution in Japan. Eighty consecutive PAH patients who underwent right heart catheterization between November 2006 and December 2018 were analyzed. Patients were classified as low, intermediate, or high risk by using a simplified version of the risk assessment that included seven variables: World Health Organization functional class, 6-min walking distance, peak oxygen consumption, brain natriuretic peptide, right atrial pressure, mixed venous oxygen saturation, and cardiac index. The high-risk group showed significantly higher mortality than the low- or intermediate-risk group at baseline (P < 0.001 for both comparisons), and the mortalities in the intermediate- and low-risk groups were both low (P = 0.989). At follow-up, patients who improved to or maintained a low-risk status showed better survival than those who did not (P = 0.041). Our data suggest that this risk assessment can predict higher mortality risk and long-term survival in PAH patients in Japan.

scholarly journals COVID-19 pandemic challenges: on the way to overcome obstacles in realization of PAH-specific therapy treatment goals

2021 ◽  
pp. 80-86
Author(s):  
E. A. Rezukhina ◽  
I. Z. Korobkova ◽  
N. M. Danilov ◽  
V. V. Gramovich ◽  
T. V. Martynyuk
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Exercise Tolerance ◽  
World Health ◽  
Treatment Goals ◽  
Specific Therapy ◽  
Risk Status ◽  
Pulmonary Arterial ◽  
Clinical Worsening

Our observation demonstrates a case of a 40-year-old female with idiopathic pulmonary arterial hypertension World Health Organization functional class III, who was admitted to NMRC of Cardiology repeatedly due to disease progression including dyspnea worsening and exercise tolerance decrease after previous COVID-19 infection on riociguat (7.5 mg daily), macitentan (10 mg daily) and selexipag (1600 mcg daily) therapy. Clinical examination demonstrated high-risk status according to the expected 1-year mortality. Due to unreleased treatment goals and high-risk status, we performed transition from selexipag to inhale iloprost. After therapy escalation the patient demonstrated a significant improvement in clinical condition, dyspnea reduction and exercise tolerance increase. The current treatment strategy for pulmonary arterial hypertension is based on regular multiparametric risk stratification approach in PAH patients. The impact of COVID-19 may become an important cause of clinical worsening in PAH patients during COVID-19 pandemic. Directed on vasodilatation and antiproliferation mechanisms of action of PAH-specific drugs are supposed to be protective in COVID-19 patients. However, the probability of clinical worsening in PAH patients despite PAH-specific therapy intake needs to be closely monitored to perform timely treatment correction in order to achieve low-risk status and to improve the prognosis of PAH patients.

scholarly journals Poor outcome of patients with pulmonary arterial hypertension with insufficient response to phosphodiesterase-5 inhibitors alone or in combination with other specific therapy: a registry-based study

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402095855
Author(s):  
Clara Hjalmarsson ◽  
Oisin Butler ◽  
Roger Hesselstrand ◽  
Katsiaryna Holl ◽  
Kjell Jansson ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
World Health Organisation ◽  
Functional Class ◽  
World Health ◽  
Walking Distance ◽  
Phosphodiesterase 5 Inhibitors ◽  
Pulmonary Arterial ◽  
Phosphodiesterase 5

Phosphodiesterase-5 inhibitors are commonly used in pulmonary arterial hypertension but, as suggested by the RESPITE study, phosphodiesterase-5 inhibitor therapy (mono-/combination) does not always have a satisfactory treatment effect. This study aimed to investigate the clinical course of pulmonary arterial hypertension patients not at treatment goal after at least 90 days of treatment with phosphodiesterase-5 inhibitors, alone or in combination with other pulmonary arterial hypertension therapies. The study included 106 incident patients from the Swedish Pulmonary Arterial Hypertension Registry, treated with phosphodiesterase-5 inhibitors for ≥90 days, who were not at a pre-specified treatment goal, i.e. in World Health Organisation functional class III, with 6-min walking distance 165–440 m, and N-terminal prohormone of brain natriuretic peptide >300 ng/L. Changes in World Health Organisation functional class, 6-min walking distance, N-terminal prohormone of brain natriuretic peptide, and risk group between index and follow-up were assessed. Of patients with complete follow-up data, ( n = 53) 77% were on combination therapy and risk assessment yielded 98% at intermediate risk at index. At follow-up, 11 patients transitioned from World Health Organisation functional class III to World Health Organisation functional class II, the median (Q1; Q3) change in 6-min walking distance was 6 (−30; 42) meters and in N-terminal prohormone of brain natriuretic peptide 47 (−410; 603) ng/L, while 89% remained at an intermediate risk. Of those without complete follow-up data, 11 patients died and 2 underwent lung transplantation. In conclusion, pulmonary arterial hypertension patients treated with phosphodiesterase-5 inhibitors, as single or combination therapy and not achieving the pre-specified treatment goals after ≥90 days have an unfavourable clinical course.

scholarly journals EXPRESS: Effect of Spironolactone use in Pulmonary Arterial Hypertension – Analysis from Pivotal Trial Databases

2021 ◽  
pp. 204589402110456
Author(s):  
Zeenat Safdar ◽  
Eunah Cho
Keyword(s):  
Heart Failure ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Patient Population ◽  
Severe Heart Failure ◽  
Functional Class ◽  
World Health ◽  
Vascular Pathology ◽  
Pulmonary Arterial ◽  
Clinical Worsening

Spironolactone, a common diuretic used in the treatment of pulmonary arterial hypertension (PAH), improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function within pulmonary endothelial cells. Spironolactone has demonstrated vascular remodeling properties and reduced all-cause mortality in patients with severe heart failure. Despite widespread use, however, its effect on morbidity and mortality in PAH have not been fully explored. A large cohort of PAH patients from a harmonized dataset from four pivotal trials were analyzed to characterize the patient population and outcomes associated with spironolactone treatment. Of 1,229 evaluable patients, 74% female, mean age 47±15yrs, baseline six-minute walk distance (6MWD) 345±74m and 75% World health Organization (WHO) functional class (FC) III/IV. Of the patients receiving spironolactone, 43% were on subcutaneous treprostinil, compared to 29.9% of patients who were not receiving spironolactone. Long-term spironolactone-treated PAH patients were older (P=0.01), had lower baseline 6MWD (P=0.01) and cardiac index (P<0.01), higher baseline Borg dyspnea score (P=0.01), WHO functional class, and right arterial pressure (P<0.01). Spironolactone patients tended to have higher hazard of clinical worsening (P<0.01). However, propensity analysis, when controlled for disease severity, showed that spironolactone treated patients did not demonstrate improved outcomes, in terms of survival and clinical worsening. Across studies, the current analysis has demonstrated that the actions of spironolactone within the context of the PAH disease process may differ from its action in CHF patients. Despite the results reported with spironolactone use in patients with left heart disease, these findings may not translate to right heart failure and pulmonary vascular pathology as similar outcomes have not necessarily been recognized in the PAH patient population. Future studies are needed to explore these findings further.

scholarly journals Severe pulmonary hypertension in lung disease: phenotypes and response to treatment

2015 ◽  
Vol 46 (5) ◽  
pp. 1378-1389 ◽  
Author(s):  
Melanie J. Brewis ◽  
Alistair C. Church ◽  
Martin K. Johnson ◽  
Andrew J. Peacock
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Disease ◽  
Functional Class ◽  
World Health ◽  
Response To Treatment ◽  
Walking Distance ◽  
Vasodilator Therapy ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ≥35 mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e.pulmonary arterial hypertension) with PH-targeted therapies is unknown.We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators.Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort.In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596 pg·mL−1(p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1 s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease.

scholarly journals Upfront triple combination therapy in severe paediatric pulmonary arterial hypertension

2020 ◽  
pp. 2001120
Author(s):  
Meindina G. Haarman ◽  
Marilyne Lévy ◽  
Marcus T.R. Roofthooft ◽  
Johannes M. Douwes ◽  
Theresia R. Vissia-Kazemier ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
World Health ◽  
Walking Distance ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Long Term Outcome ◽  
Pulmonary Arterial

IntroductionTreatment strategies in paediatric pulmonary arterial hypertension (PAH) have evolved over the last years, but survival is still poor. Recently, in adults with severe PAH, upfront triple combination therapy (uTCT) from diagnosis has been reported to show significant clinical improvement and excellent long-term outcome. This retrospective, observational study aimed to assess the efficacy of uTCT in paediatric PAH.MethodsChildren diagnosed with PAH between 2010 and 2019 and started with uTCT were included. World Health Organization Functional Class (WHO-FC), haemodynamics, echocardiography, six-minute walking distance, and serum level of N-terminal-Pro-Brain-Natriuretic-Peptide were assessed at baseline, after three and 6 months and at last available follow-up. Events were defined as death, lung transplantation or Potts shunt.ResultsTwenty-one children (median age 4.8 years (2.5–12.8), 57% females) were included. All children except one were in WHO-FC III or IV (28% and 67%, respectively). After 3 months, one child had died and one child had received a Potts shunt. The remaining 19 children showed clinical and echocardiographic improvement, which persisted at 6 months. Children with idiopathic and heritable PAH showed one-, two-, and three-year transplant-free survival estimates of 100%, 94%, and 87%, albeit 47% of them receiving a Potts shunt during follow-up.ConclusionsChildren with severe PAH, but not pulmonary veno-occlusive disease, improved significantly with uTCT and showed beneficial up to 3-year survival rates, albeit 47% of them receiving a Potts shunt during follow-up. The role of a Potts shunt in conjunction to uTCT in paediatric PAH needs to be further established.

scholarly journals The clinical characteristics and long-term prognosis of pulmonary arterial hypertension associated with hereditary hemorrhagic telangiectasia

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401875991 ◽  
Author(s):  
Wen Li ◽  
Chang-ming Xiong ◽  
Qing Gu ◽  
Xiao-tong Wang ◽  
Xiao-ling Cheng ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Cardiac Index ◽  
Arterial Hypertension ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Clinical Characteristics ◽  
Total Bilirubin ◽  
World Health ◽  
Pulmonary Arterial ◽  
Long Term Prognosis

Pulmonary arterial hypertension (PAH) is a severe complication of hereditary hemorrhagic telangiectasia (HHT); however, little is known about its clinical characteristics and prognosis. Nine newly diagnosed HHT-PAH patients were prospectively recruited between October 2007 and January 2016 and were followed up every half-year. Eighteen idiopathic pulmonary arterial hypertension (IPAH) patients, matched with HHT-PAH patients on mean pulmonary arterial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, and World Health Organization (WHO) functional class (FC), were recruited. The clinical characteristics of HHT-PAH patients were described and the prognosis of these two cohorts were compared. Of HHT-PAH patients, 55.56% were WHO FC III. Kaplan–Meier survival analysis showed one- and three-year survival rates of HHT-PAH patients were 77.8% and 53.3% respectively, which were worse than matched IPAH patients (log rank: P = 0.047). HHT-PAH patients had higher red cell distribution width (14.88 ± 2.93% versus 13.19 ± 0.83%, P = 0.031), larger right ventricular anteroposterior diameter (34.67 ± 6.67 mm versus 28.56 ± 6.35 mm, P = 0.029), and lower mean corpuscular hemoglobin concentration (317.38 ± 17.71 g/L versus 335.72 ± 14.68 g/L, P = 0.011) than matched IPAH patients. Multivariate Cox proportional hazards regression analyses showed baseline total bilirubin independently predicted the mortality of HHT-PAH after adjusting by age, cardiac index, mixed venous oxygen saturation, or serum uric acid. HHT-PAH patients may have a worse prognosis than matched IPAH patients. Baseline total bilirubin may be a promising predictor for the long-term prognosis in HHT-PAH patients.

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