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Turkish Society of Cardiology
Young Cardiologists
President
Dr. Muzaffer Değertekin
Coordinator for the
Board of Directors
Dr. Ertuğrul Okuyan
Coordinator for the
Board of Directors
Dr. Can Yücel Karabay
Members
Dr. Adem Aktan
Dr. Gülşah Aktüre
Dr. Bayram Arslan
Dr. İnanç Artaç
Dr. Ahmet Oğuz Aslan
Dr. Görkem Ayhan
Dr. Ahmet Anıl Başkurt
Dr. Özkan Bekler
Dr. Oğuzhan Birdal
Dr. Yusuf Bozkurt Şahin
Dr. Serkan Bulgurluoğlu
Dr. Ümit Bulut
Dr. Veysi Can
Dr. Mustafa Candemir
Dr. Murat Çap
Dr. Göksel Çinier
Dr. Ali Çoner
Dr. Yusuf Demir
Dr. Ömer Furkan Demir
Dr. Murat Demirci
Dr. Ayşe İrem Demirtola Mammadli
Dr. Süleyman Çağan Efe
Dr. Mehmet Akif Erdöl
Dr. Kubilay Erselcan
Dr. Kerim Esenboğa
Dr. Duygu Genç
Dr. Kemal Göçer
Dr. Elif Güçlü
Dr. Arda Güler
Dr. Duygu İnan
Dr. Hasan Burak İşleyen
Dr. Muzaffer Kahyaoğlu
Dr. Sedat Kalkan
Dr. Yücel Kanal
Dr. Özkan Karaca
Dr. Ahmet Karaduman
Dr. Mustafa Karanfil
Dr. Ayhan Kol
Dr. Fatma Köksal
Dr. Mevlüt Serdar Kuyumcu
Dr. Yunus Emre Özbebek
Dr. Ahmet Özderya
Dr. Yasin Özen
Dr. Ayşenur Özkaya İbiş
Dr. Çağlar Özmen
Dr. Selvi Öztaş
Dr. Hasan Sarı
Dr. Serkan Sivri
Dr. Ali Uğur Soysal
Dr. Hüseyin Tezcan
Dr. Nazlı Turan
Dr. Berat Uğuz
Dr. Örsan Deniz Urgun
Dr. İdris Yakut
Dr. Mustafa Yenerçağ
Dr. Mehmet Fatih Yılmaz
Dr. Yakup Yiğit
Dr. Mehmet Murat Yiğitbaşı
Bulletin Editors
Dr. Muzaffer Değertekin
Dr. Bülent Mutlu
Dr. Süleyman Çağan Efe
Dr. Duygu İnan
Dr. Alper Karakuş
Dr. Sedat Kalkan
Dr. Göksel Çinier
Contributors
Dr. Selin Çakır
Dr. Ezgi Güzel
Dr. Numan Kılıç
Dr. Cansu Öztürk
Dr. Bilal Ülker
Dr. Gözde Yılmaz
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The STELLAR Phase III Trial: A Study Of Sotatercept In Combination With Background Therapy For The Treatment Of Pulmonary Arterial HypertensionTürk Kardiyoloji Derneği Genç Kardiyologlar Bülteni - The STELLAR Phase III Trial: A Study Of Sotatercept In Combination With Background Therapy For The Treatment Of Pulmonary Arterial Hypertension (Dr. Cansu Öztürk)The STELLAR Phase III Trial: A Study Of Sotatercept In Combination With Background Therapy For The Treatment Of Pulmonary Arterial Hypertension
Dr. Cansu Öztürk
Published in Congress: ACC 2023
Link: https://www.acc.org/-/media/Clinical/PDF-Files/Approved-PDFs/2023/03/04/ACC23/06Mar/12pm-STELLAR-Phase-III-acc-2023.pdf
Full text has been published in NEJM.
Background:
Pulmonary Arterial Hypertension (PAH) is a progressive disease caused by pulmonary vascular remodeling due to imbalance in pro-proliferative (ActRIIA-mediated) and anti-proliferative (BMPR-II-mediated) signaling pathways, resulting in excessive proliferation of vessel wall cells. The therapeutic use of Sotatercept, an activin signaling inhibitor, has been proposed to act as a reverse remodeling agent through rebalancing of anti-proliferative and pro-proliferative signaling pathways.
Objective:
The goal of the trial was to compare the safety and efficacy of sotatercept in addition to basic PAH therapy (monotherapy, dual therapy, or triple therapy consisting of endothelin receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE5i), soluble guanylate cyclase stimulator, and/or prostacyclin analogues) in patients with symptomatic PAH.
Methods:
It is a multicenter, double-blind, randomized, placebo-controlled phase 3 study in which a total of 323 subjects were included, with a female ratio of 79% and a mean age of 47.9 years. Patients were randomized 1:1 to sotatercept (n = 163) or placebo (n = 160) for 24 weeks. Sotatercept was administered as an initial dose of 0.3 mg/kg and was increased to 0.7 mg/kg every 3 weeks. Patients were classified according to World Health Organization (WHO) functional class and baseline PAH therapy.
Primary endpoint; It is the change from baseline in the 6MWT distance at week 24. Secondary endpoints were; multicomponent improvement, change in PVR, change in NT-proBNP level, improvement in WHO functional class, time to death or clinical worsening, change in French risk score and PAH-SYMPACT score. Inclusion criteria: Group 1 PAH, WHO functional capacity 2 or 3, ?18 years, baseline PVR?400 dynes/sec/cm-5 and PCWP or LVEDP ?15 mmHg, 6MWD 150-500 m, stable treatment with baseline PAH therapy.
Results:
The median change from baseline in 6MWD distance at week 24 was 34.4 m (95% CI, 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, -0.3 to 3.5) in the placebo group. The Hodges-Lehmann estimate of the difference between these distances is 40.8 m (95% CI, 27.5 vs 54.1; P<0.001). Secondary endpoints other than PAH-SYMPACT improved significantly with sotatercept compared to placebo, while the PAH-SYMPACT Cognitive-Emotional Domain score did not improve. Sotatercept reduced the risk of death and non-fatal clinical worsening events by 84% compared to placebo (HR: 0.16 [95% CI: 0.08 to 0.35]). Side effects that occur more frequently with sotatercept than with placebo; epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.
Conclusion:
In patients with pulmonary arterial hypertension receiving stable baseline PAH therapy, sotatercept resulted in a significant improvement in exercise capacity (6MWD) compared to placebo. These results demonstrated the clinical benefit of sotatercept, approved as a new treatment for PAH, in combination with PAH treatments.
Interpretations:
This study demonstrates that sotatercept, an activin signaling inhibitor, is superior to placebo in improving 6MWD in adults with symptomatic PAH with baseline PAH therapy. There has also been an improvement in all cause mortality and clinical events. However, bleeding events were more frequent with sotatercept. Sotatercept is promising to find a place for itself as a new agent in the treatment of PAH, given its clinical improvement benefit.
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