1,721,123 research outputs found
Langzeitergebnisse der pulmonalen Ballonangioplastie bei Patienten mit chronisch thromboembolischer pulmonaler Hypertonie
Full text linkDie CTEPH ist eine seltene, jedoch schwerwiegende und progredient verlaufende Lungenerkrankung, die häufig mit einer vorangegangenen Lungenarterienembolie assoziiert ist. Die Zeitspanne von Symptombeginn zur Stellung der richtigen Diagnose ist prognosebestimmend und bisher mit durchschnittlich 14 Monaten noch relativ lang.
Pathophysiologisch steht eine Makrovaskulopathie der präkapillären Lungenstrombahn mit konsekutiver fortschreitender Mikrovaskulopathie im Vordergrund. Dies führt langfristig zu einer rechtskardialen Fehlanpassung mit progredienter Dyspnoe und letztlich irreversiblem Rechtsherzversagen.
Diagnostisch wegweisend ist neben der klinischen Symptomatik zunächst die transthorakale Echokardiographie mit Hinweisen auf eine pulmonale Hypertonie und ggf. eine Spiroergometrie.
Weiter bestätigt werden kann die PH durch eine Ventilations-/Perfusions-Szintigraphie, wodurch Diskrepanzen der Perfusion und Ventilation der Lunge aufgedeckt werden können. Nach Überweisung an ein PH-/CTEPH-Zentrum erfolgt die weitere spezifische Diagnostik bestehend aus Rechtsherzkatheter, CT-Angiographie sowie Pulmonalisangiographie.
Neben einer supportiven Sauerstofftherapie bei Bedarf und kardiovaskulärem Training ist eine lebenslange Antikoagulation fester Bestandteil der Therapie. Zudem hat sich die medikamentöse Therapie mit Riociguat dem Stimulator der löslichen Guanylatzyklase als Bestandteil der medikamentösen Therapie etabliert.
Als mechanische Therapieoptionen stehen die pulmonale Endarteriektomie sowie die pulmonale Ballonangioplastie zur Verfügung. Die pulmonale Endarteriektomie kann aufgrund der Lokalisation der Makroangiopathie nur etwa zwei Drittel der Patienten angeboten werden. In dieser Arbeit konnte gezeigt werden, dass die BPA sowohl die hämodynamischen Parameter als auch die kardiopulmonale Leistungsfähigkeit und die Symptomatik der Patienten verbessert. Zudem zeigte sich ein deutlicher Überlebensvorteil gegenüber Patienten ohne Intervention im historischen Vergleich, wenngleich der Stellenwert der medikamentösen Therapie mit Riociguat nicht eindeutig herausgearbeitet werden konnte.
Dabei bleiben die mittelfristigen Vorteile der BPA, insbesondere die Verbesserung der Lebensqualität, über einen Zeitraum von bis zu fünf Jahren erhalten.Sonstige Drittmittelgeber/-inne
Komplikationen der pulmonalen Ballonangioplastie bei Patienten mit inoperabler chronisch thromboembolischer pulmonaler Hypertonie
Full text linkHintergrund: Die pulmonale Ballonangioplastie (BPA) ist ein bislang noch wenig evidenzbasiertes Verfahren zur Behandlung inoperabler CTEPH. Das nach anfänglich hoher Komplikationsrate wieder verlassene Verfahren gewann nach Optimierung innerhalb der letzten Jahre wieder an Bedeutung. Ziel dieser Studie ist es, stattgehabte Komplikationen zu untersuchen und risikoadäquat einzuordnen.
Methoden: Es erfolgte die retrospektive Datenanalyse von insgesamt 142 Patienten, die an der Kerckhoff-Klinik in Bad Nauheim zwischen März 2014 und Dezember 2019 mittels BPA behandelt wurden und sich einer 6-Monats-Follow-up Untersuchung unterzogen haben. Darüber hinaus wurden Interventionen der 142 Patienten, sowie weiterer 93 Patienten betrachtet, um einen Lernprozess der praktizierenden Untersucher abzubilden.
Ergebnisse: Als Prädisposition für das vermehrte Auftreten von Komplikationen zeigte sich ein erhöhter Baseline PVR (Cut-off >6,6 WU), sowie ein erhöhtes NT-proBNP. Doch auch das entsprechende Patientenkollektiv profitiert messbar von der Durchführung einer BPA. Darüber hinaus zeigt sich eine Lernkurve mit zunehmender Erfahrung der Untersucher.
Zusammenfassung: Bei den im Rahmen der BPA auftretenden Komplikationen handelt es sich vornehmlich um gut beherrschbare Blutungskomplikationen. Im mittelfristigen Verlauf lässt sich ein funktioneller Benefit, auch bei Patienten mit stattgehabten Komplikationen, nachweisen. Das Verfahren sollte Expertenzentren mit entsprechender Erfahrung vorbehalten sein
Use of clinically relevant responder threshold criteria to evaluate the response to treatment in the Phase III PATENT-1 study
No full textBackgroundIn PATENT-1, riociguat significantly improved 6-minute walking distance (6MWD) and a range of secondary end-points in patients with pulmonary arterial hypertension (PAH). We investigated whether riociguat increased the proportion of patients achieving clinically relevant responder thresholds compared with placebo during PATENT-1.MethodsIn PATENT-1, a randomized, double-blind study, treatment-naïve patients or patients on background PAH-targeted therapy with symptomatic PAH received 12 weeks of treatment with placebo, riociguat up to 2.5 mg 3 times daily, or riociguat up to 1.5 mg 3 times daily. Increases in 6MWD ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liter/min/m2, mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg were chosen as threshold criteria of a positive response.ResultsRiociguat increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy with 6MWD ≥380 m at Week 12 (+21% and +15%, respectively), whereas there was a small reduction in 6MWD in placebo-treated patients for both sub-groups. Riociguat also increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy achieving World Health Organization functional class I/II (+12% and +19%, respectively) and cardiac index ≥2.5 liter/min/m2 (+30% and +33%, respectively) at Week 12, whereas there was little change in the respective placebo groups.ConclusionsCompared with placebo, riociguat increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy who fulfilled criteria defining a positive response to therapy
Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension
No full textIntroduction: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data. Methods: MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup). Results: Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was − 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup. Conclusion: These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged. Trial Registration: ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721
Riociguat for the treatment of pulmonary arterial hypertension: A long-term extension study (patent-2)
No full textAbstract
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 yea
Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension.
No full textOBJECTIVE:
We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 study.
METHODS:
Patients with inoperable or persistent/recurrent CTEPH (n=261; mean± SD age 59±14 years; 66% women) were randomised to riociguat (up to 2.5 mg three times daily) or placebo. Haemodynamic parameters were assessed at baseline and week 16.
RESULTS:
Riociguat decreased pulmonary vascular resistance (PVR) in inoperable (n=189; least-squares mean difference: -285 dyn s/cm5 (95% CI -357 to -213); p<0.0001) and persistent/recurrent (n=72; -131 dyn s/cm5 (95% CI -214 to -48); p=0.0025) patients. Cardiac index improved in inoperable patients by a least-squares mean difference of +0.6 L/min/m2 (95% CI 0.4 to 0.7; p<0.0001), while in persistent/recurrent patients the change was +0.2 L/min/m2 (95% CI -0.1 to 0.5; p=0.17). Mean pulmonary artery pressure decreased in inoperable and persistent/recurrent patients(-4.7 mm Hg (95% CI -6.9 to -2.6; p<0.0001 and -4.8 mm Hg (-8.2 to -1.5; p=0.0055), respectively). For all patients, changes in 6 min walk distance correlated with changes in PVR (r=-0.29 (95% CI -0.41 to -0.17); p<0.0001) and cardiac index (r=0.23 (95% CI 0.10 to 0.35); p=0.0004).
CONCLUSIONS:
Riociguat improved haemodynamics in patients with inoperable CTEPH or persistent/recurrent CTEPH
Effect of macitentan on hospitalizations: Results from the SERAPHIN trial
No full textOBJECTIVES:
This study sought to evaluate the effect of macitentan on hospitalization of patients with symptomatic pulmonary arterial hypertension (PAH).
BACKGROUND:
PAH is a progressive, life-threatening disease often requiring hospitalization.
METHODS:
In the multicenter, double-blind, randomized, event-driven, phase III SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial, patients with symptomatic PAH were randomized (1:1:1) to receive placebo or 3 mg or 10 mg of macitentan. Effects of macitentan on the risk, rate, and number of hospital days for all-cause and PAH-related hospitalizations were compared with those for placebo. Risk and causes of hospitalizations unrelated to PAH were investigated.
RESULTS:
Of 742 randomized patients, 250 received placebo, 250 received 3 mg of macitentan, and 242 received 10 mg of macitentan; the overall median duration of treatment was 115 weeks. Risk of all-cause hospitalization was reduced by 18.9% (p = 0.1208) and 32.3% (p = 0.0051) in the macitentan 3-mg and 10-mg arm, respectively. Rates of all-cause hospitalizations and numbers of hospital days were reduced by 20.5% (p = 0.0378) and 30.6% (p = 0.0278), respectively, with 3 mg of macitentan and by 33.1% (p = 0.0005) and 31.0% (p = 0.0336), respectively, with 10 mg of macitentan. Risk of PAH-related hospitalizations were reduced by 42.7% (p = 0.0015) and 51.6% (p < 0.0001) in the macitentan 3-mg and 10-mg arms, respectively. Rate of PAH-related hospitalizations and numbers of hospital days were reduced by 44.5% (p = 0.0004) and 53.3% (p = 0.0001), respectively, with 3 mg of macitentan, and reduced by 49.8% (p < 0.0001) and 52.3% (p = 0.0003), respectively, with 10 mg of macitentan. Risk of non-PAH-related hospitalization was similar between treatment arms.
CONCLUSIONS:
Macitentan 10 mg significantly reduced the risk and rate of all-cause hospitalization, which was driven by reductions in the risk and rate of PAH-related hospitalization. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertensio
Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial
No full textBackground Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. Methods Patients were randomized to placebo, macitentan 3 mg, or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline, at month 6 and month 12, and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed. Results At month 6, macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio [HR], 0.60; 95% CI, 0.47-0.76; P < .0001) and MCS scores (HR, 0.76; 95% CI, 0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score. Conclusions Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown. Trial Registry ClinicalTrials.gov; No.: NCT00660179; URL: clinicaltrials.gov
Incident and prevalent cohorts with pulmonary arterial hypertension: Insight from SERAPHIN
No full textAbstract
In SERAPHIN, a long-term, randomised, controlled trial (NCT00660179) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation. We evaluated disease progression and the effect of macitentan in treatment-naïve incident and prevalent cohorts.Patients allocated to placebo, or macitentan 3 mg or 10 mg were classified by time from diagnosis to enrolment as incident (≤6 months; n=110) or prevalent (>6 months; n=157). The risk of morbidity/mortality and PAH-related death/hospitalisation was determined using Cox regression.The risk of morbidity/mortality (Kaplan-Meier estimates at month 12: 54.4% versus 26.7%; p=0.006) and PAH-related death/hospitalisation (Kaplan-Meier estimates at month 12: 47.3% versus 19.9%; p=0.006) were significantly higher for incident versus prevalent patients receiving placebo, respectively. There was no significant difference in the risk of all-cause death between incident and prevalent cohorts (p=0.587). Macitentan 10 mg significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation versus placebo in incident and prevalent cohorts.Incident patients had a higher risk for PAH progression compared with prevalent patients but not a higher risk of death. Macitentan delayed disease progression in both incident and prevalent PAH patients
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