Abstract
Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Methods: Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. Findings: 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Interpretation: Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers.
| Original language | English |
|---|---|
| Pages (from-to) | 372-380 |
| Number of pages | 9 |
| Journal | The Lancet Respiratory Medicine |
| Volume | 4 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2016 |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
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Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension : Data from the CHEST-2 open-label, randomised, long-term extension trial. / Simonneau, Gérald; D'Armini, Andrea M.; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Jansa, Pavel; Kim, Nick H.; Mayer, Eckhard; Pulido, Tomas; Wang, Chen; Colorado, Pablo; Fritsch, Arno; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M.
In: The Lancet Respiratory Medicine, Vol. 4, No. 5, 01.05.2016, p. 372-380.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension
T2 - Data from the CHEST-2 open-label, randomised, long-term extension trial
AU - Simonneau, Gérald
AU - D'Armini, Andrea M.
AU - Ghofrani, Hossein Ardeschir
AU - Grimminger, Friedrich
AU - Jansa, Pavel
AU - Kim, Nick H.
AU - Mayer, Eckhard
AU - Pulido, Tomas
AU - Wang, Chen
AU - Colorado, Pablo
AU - Fritsch, Arno
AU - Meier, Christian
AU - Nikkho, Sylvia
AU - Hoeper, Marius M.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Methods: Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. Findings: 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Interpretation: Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers.
AB - Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Methods: Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. Findings: 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Interpretation: Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers.
UR - http://www.scopus.com/inward/record.url?scp=84963584369&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963584369&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(16)30022-4
DO - 10.1016/S2213-2600(16)30022-4
M3 - Article
AN - SCOPUS:84963584369
VL - 4
SP - 372
EP - 380
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
SN - 2213-2600
IS - 5
ER -