Response to exercise in patients with pulmonary arterial hypertension treated with combination therapy

Pulmonary arterial hypertension (PAH) -specific combination therapy improves pulmonary haemodynamics at rest in patients with PAH; nevertheless, exertional dyspnoea remains. We investigated pulmonary haemodynamic response to exercise, and the relation to ventilatory efficiency and hypoxemia in patients with PAH treated with combination therapy. Thirty-two clinically stable patients with PAH undergoing combination therapy underwent cardiopulmonary exercise testing with right-heart catheterisation. Haemodynamic impairment was moderate-to-severe before treatment. However, it was significantly improved, and in 13 patients after treatment, the mean pulmonary arterial pressure (mPAP) at rest was <25 mmHg. The mPAP significantly increased from 27.9±10.7 to 45.9±16.7 mmHg (p<0.01) during exercise. The cardiac index increased inadequately, and the total pulmonary resistance (TPR) significantly increased from 5.74±3.42 to 6.58±3.82 Wood units (p<0.01). The mPAP/cardiac output (CO) slope was steep (10.0±6.7 mmHg·L−1·min−1). It significantly correlated with both the minute ventilation/carbon dioxide output slope (r=0.51, p<0.01) and peripheral arterial oxygen saturation/workload slope (r=−0.41, p=0.02). The mPAP/CO slope also significantly correlated with mPAP at rest (r=0.73, p<0.01) and TPR at rest (r=0.64, p<0.01). Even after pulmonary haemodynamics at rest was significantly improved in PAH patients with PAH-specific combination therapy, the mPAP/CO slope was steep and the steep mPAP/CO slope related to decreased ventilatory efficiency and the severity of hypoxemia. The mPAP/CO slope was steeper in patients with higher mPAP and TPR at rest.

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Creation of a restrictive atrial communication in pulmonary arterial hypertension (PAH): effective palliation of syncope and end-stage heart failure

Pulmonary Circulation ◽

10.1177/2045894018776518 ◽

2018 ◽

Vol 8 (2) ◽

pp. 204589401877651 ◽

Cited By ~ 5

Author(s):

Anna Bauer ◽

Markus Khalil ◽

Dorle Schmidt ◽

Jürgen Bauer ◽

Anoosh Esmaeili ◽

...

Keyword(s):

Heart Failure ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Arterial Oxygen Saturation ◽

Hypertensive Crisis ◽

Specific Treatment ◽

Arterial Oxygen ◽

Pulmonary Arterial ◽

The Mean ◽

End Stage

Atrial septostomy (AS) is recommended for pulmonary arterial hypertension (PAH)-associated right ventricular (RV) failure, recurrent syncope, or pulmonary hypertensive crisis (PHC). We aimed to evaluate the feasibility and efficacy of AS to manage PAH from infancy to adulthood. From June 2009 to December 2016, transcatheter atrial communications were created in 11 PAH patients (4 girls/women; median age = 4.3 years; range = 33 days–26 years; median body weight = 14 kg; range = 3–71 kg; NYHA-/Ross class IV; n = 11). PAH was classified as idiopathic (n = 6) or secondary (n = 5). History of syncope was dominant (n = 6); two with patent foramen ovale (PFO) admitted with recurrent PHC, three patients required resuscitation before AS. Three patients had PAH-associated low cardiac output. The average pulmonary arterial pressures (PAP systolic/diastolic) were 101/50 (±34/23); the corresponding systemic arterial pressures (SAP) were 99/54 (±23/11); and the mean ratio of PAPd / SAPd was 0.97 (±0.4). Percutaneous trans-septal puncture was uneventfully performed in nine patients; a PFO was dilated in two patients. There was no procedure-related mortality. The median balloon size was 10 mm (range = 6–14 mm); the mean catheter time was 174.6 ± 48 min; fluoroscopy time was 19.8 (±11) min. Syncope and PHC were successfully treated in all patients. The mean arterial oxygen saturation decreased from 97 ± 2 to 89 ± 11.7. One patient died awaiting lung transplantation, one continues to be listed; two patients received a reverse Potts-shunt, one patient died during follow-up; seven patients are stable with PAH-specific treatment. Percutaneous AS is an effective method palliating PAH-associated syncope, PHCs or right (bi-) ventricular heart failure.

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Effect of Combination Therapy of Endothelin Receptor Antagonist and Phosphodiesterase-5 Inhibitor on Clinical Outcome and Pulmonary Haemodynamics in Patients with Pulmonary Arterial Hypertension: A Meta-Analysis

Clinical Drug Investigation ◽

10.1007/s40261-019-00841-1 ◽

2019 ◽

Vol 39 (11) ◽

pp. 1031-1044 ◽

Cited By ~ 1

Author(s):

Lopamudra Kirtania ◽

Rituparna Maiti ◽

Anand Srinivasan ◽

Archana Mishra

Keyword(s):

Pulmonary Arterial Hypertension ◽

Combination Therapy ◽

Clinical Outcome ◽

Arterial Hypertension ◽

Receptor Antagonist ◽

Meta Analysis ◽

Endothelin Receptor ◽

Pulmonary Haemodynamics ◽

Pulmonary Arterial ◽

Phosphodiesterase 5

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Sildenafil for Asian Adult Patients with Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-498117/v1 ◽

2021 ◽

Author(s):

Qianling Shi ◽

Zijun Wang ◽

Nan Yang ◽

Yanfang Ma ◽

Yaolong Chen ◽

...

Keyword(s):

Systematic Review ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Arterial Oxygen Saturation ◽

Symptomatic Treatment ◽

Adult Patients ◽

Arterial Oxygen ◽

Cochrane Library ◽

Number Of Patients ◽

Pulmonary Arterial

Abstract Background: The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was beneficial, but the dose varies greatly. We aimed to evaluate sildenafil effectiveness and safety in dose of 20mg/three times a day (TID) for Asian adult patients with PAH. Methods: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane Library, CBM, CNKI and Wanfang Data) from their inception to May 2020 were searched. We included all randomized controlled trials and non-randomized studies of interventions that comparing sildenafil (20mg/TID) versus placebo or symptomatic treatment for PAH Asian adults. Results: Eight studies totaling 364 participants were included. When compared to symptomatic treatment, sildenafil treated patients were more likely to walk 68.3 meters further in six-minute walk distance [mean difference (MD)=68.3 meters, 95% confidence interval (CI) 48.85 to 87.76, P＜0.00001], to achieve an improvement in systemic arterial oxygen saturation (MD=2.48%, 95% CI 1.26 to 3.71, P＜0.00001) and in score on the Borg scale of dyspnea (MD=-0.99 points, 95% CI -1.45 to -0.53, P＜0.00001). The total number of patients with WHO class III and IV also showed downtrend. When compared to placebo, sildenafil was associated with a greater reduction in the mean pulmonary artery pressure (MD=-4.13 mmHg, 95% CI -6.52 to -1.74, P=0.0007) and level of brain natriuretic peptide (MD=-86.16 pg /mL, 95% CI -103.39 to -68.93, P＜0.00001). The most adverse reactions were headache, flushing, dyspepsia, and diarrhea, which were relatively mild. Conclusions: Sildenafil in dose of 20mg/TID is well tolerated in Asian adults with PAH, and associated with statistically significant improvements in exercise capacity, cardio-pulmonary function and haemodynamic indices. The long-term prognosis still needs to be evaluated and confirmed by further trials.Systematic review registration: PROSPERO CRD42020190582

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Should oral combination therapy be the standard of care for pulmonary arterial hypertension?

Expert Review of Respiratory Medicine ◽

10.1080/17476348.2020.1722641 ◽

2020 ◽

Vol 14 (4) ◽

pp. 341-343

Author(s):

Aiko Ogawa ◽

Hiromi Matsubara

Keyword(s):

Pulmonary Arterial Hypertension ◽

Combination Therapy ◽

Arterial Hypertension ◽

Standard Of Care ◽

Pulmonary Arterial

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Temporal trends in pulmonary arterial hypertension: Results from the COMPERA registry

European Respiratory Journal ◽

10.1183/13993003.02024-2021 ◽

2021 ◽

pp. 2102024

Author(s):

Marius M. Hoeper ◽

Christine Pausch ◽

Ekkehard Grünig ◽

Gerd Staehler ◽

Doerte Huscher ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Combination Therapy ◽

Arterial Hypertension ◽

Temporal Trends ◽

Survival Rates ◽

Term Survival ◽

Pulmonary Arterial ◽

Early Combination Therapy

BackgroundSince 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extend this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival.MethodsWe analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we look at annualized data and at cumulated data comparing the periods 2010–2014 and 2015–2019.ResultsA total of 2,531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010–2014 and 2015–2019 periods, 1-year survival estimates were similar (89.0% [95% CI, 87.2%, 90.9%] and 90.8% [95% CI, 89.3%, 92.4%]), respectively, whereas there was a slight but non-significant improvement in 3-year survival estimates (67.8% [95% CI, 65.0%, 70.8%] and 70.5% [95% CI, 67.8%, 73.4%]), respectively.ConclusionsThe use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.

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Recent advances in the management of pulmonary arterial hypertension

F1000Research ◽

10.12688/f1000research.9739.1 ◽

2016 ◽

Vol 5 ◽

pp. 2755 ◽

Cited By ~ 12

Author(s):

Halley Tsai ◽

Yon K. Sung ◽

Vinicio de Jesus Perez

Keyword(s):

Pulmonary Arterial Hypertension ◽

Combination Therapy ◽

Arterial Hypertension ◽

Soluble Guanylate Cyclase ◽

Right Heart Failure ◽

New Drugs ◽

Triple Combination Therapy ◽

Treatment Naïve ◽

Treatment Paradigm ◽

Pulmonary Arterial

Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease.

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Treatment patterns, healthcare resource utilization, and healthcare costs among patients with pulmonary arterial hypertension in a real-world US database

Pulmonary Circulation ◽

10.1177/2045894018816294 ◽

2018 ◽

Vol 9 (1) ◽

pp. 204589401881629 ◽

Cited By ~ 8

Author(s):

Sean Studer ◽

Michael Hull ◽

Janis Pruett ◽

Eleena Koep ◽

Yuen Tsang ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Combination Therapy ◽

Arterial Hypertension ◽

Resource Utilization ◽

Real World ◽

Healthcare Resource ◽

Healthcare Resource Utilization ◽

Treatment Patterns ◽

Combination Therapies ◽

Pulmonary Arterial

Several new medications for pulmonary arterial hypertension (PAH) have recently been introduced; however, current real-world data regarding US patients with PAH are limited. We conducted a retrospective administrative claims study to examine PAH treatment patterns and summarize healthcare utilization and costs among patients with newly diagnosed PAH treated in US clinical practice. Patients newly treated for PAH from 1 January 2010 to 31 March 2015 were followed for ≥12 months. Patient characteristics, treatment patterns, healthcare resource utilization, and costs were described. Adherence (proportion of days covered), persistence (months until therapy discontinuation/modification), and the probability of continuing the index regimen were analyzed by index regimen cohort (monotherapy versus combination therapy). Of 1637 eligible patients, 93.8% initiated treatment with monotherapy and 6.2% with combination therapy. The most common index regimen was phosphodiesterase type 5 inhibitor (PDE-5I) monotherapy (70.0% of patients). A total of 581 patients (35.5%) modified their index regimen during the study. Most patients (55.4%) who began combination therapy did so on or within six months of the index date. Endothelin receptor agonists (ERAs) and combination therapies were associated with higher adherence than PDE-5Is and monotherapies, respectively. Healthcare utilization was substantial across the study population, with costs in the combination therapy cohort more than doubling from baseline to follow-up. The majority of patients were treated with monotherapies (most often, PDE-5Is), despite combination therapies and ERAs being associated with higher medication adherence. Index regimen adjustments occurred early and in a substantial proportion of patients, suggesting that inadequate clinical response to monotherapies may not be uncommon.

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Triple combination therapy with macitentan, riociguat, and selexipag in a patient with idiopathic pulmonary arterial hypertension (functional class III)

Kardiologiia ◽

10.18087/cardio.2021.10.n1789 ◽

2021 ◽

Vol 61 (10) ◽

pp. 104-107

Author(s):

A. A. Proshkina ◽

N. A. Tsareva ◽

G. V. Nekludova ◽

S. N. Avdeev

Keyword(s):

Pulmonary Arterial Hypertension ◽

Combination Therapy ◽

Arterial Hypertension ◽

Clinical Manifestations ◽

Functional Class ◽

Idiopathic Pulmonary Arterial Hypertension ◽

Triple Combination ◽

Class Iii ◽

Triple Combination Therapy ◽

Pulmonary Arterial

The article presents a clinical case of successful triple combination therapy in a female patient with functional class III idiopathic pulmonary arterial hypertension. Supplementing the previous macitentan and riociguat treatment with selexipag reduced the severity of clinical manifestations of pulmonary hypertension. Also, the treatment efficacy was demonstrated by improvement of laboratory and instrumental indexes. Time-related changes were evaluated at 3 months after initiation of the selexipag treatment.

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