Table 1.
Selected Randomized Controlled Studies of Pulmonary Hypertension Therapeutics in CTEPH
| Study | Intervention | No. of Patients | No. of Weeks | Primary Outcome | Other Outcomes and Conclusions |
|---|---|---|---|---|---|
| BENEFiT63 | Bosentan (vs placebo) | 157 | 16 | 6MWD (+2.9 m vs +0.8 m; P = .55); PVR (–146 dynes vs +30 dynes; P < .0001) | No significant difference in FC or time to clinical worsening. Operability was adjudicated centrally retrospectively. |
| CHEST-167 | Riociguat (vs placebo) | 261 | 16 | 6MWD (+39 m vs –6 m; P < .001) | Improved PVR (–226 dyne vs +23 dyne; P < .001), FC, mPAP, NT-proBNP with riociguat. Prospective operability adjudication. First pharmacotherapy with indication for CTEPH, approved worldwide. |
| MERIT-165 | Macitentan (vs placebo) | 80 | 16 | PVR (–206 dynes vs –86 dynes; P = .04) | Improved 6MWD (+35 m vs +1 m; P = .03), NT-proBNP, cardiac output with macitentan. Background therapy (PDE5i, oral or inhaled prostanoids) in 61%. First study with combination therapy for CTEPH (but notably riociguat not allowed). |
| CTREPH64 | Subcutaneous treprostinil (30 ng/kg/min vs 3 ng/kg/min) | 105 | 24 | 6MWD (+45 m vs +4 m; P = .002) | Improved PVR (–214 dyn vs +73 dyn; P < .0001), mPAP, cardiac output, NT-proBNP with higher-dose treprostinil. Technically operable patients included. Approved in Europe. |
| Ogo et al66 | Selexipag (vs placebo) | 78 | 20 | PVR (–98 dynes vs –5 dynes; P = .006) | Improved cardiac index and Borg dyspnea scores with selexipag. No significant difference in mPAP, 6MWD, or FC. 62% receiving background riociguat and 53% previously received BPA. Approved in Japan. |
6MWD = 6-min walk distance; BPA = balloon pulmonary angioplasty; BENEFiT = Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension; CHEST-1 = A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH. (CHEST-1); CTEPH = chronic thromboembolic pulmonary hypertension; CTREPH = Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension; FC = functional class; MERIT-1 = Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension; mPAP = mean pulmonary artery pressure; NT-proBNP = N-terminal pro–brain natriuretic peptide; PDE5 = phosphodiesterase type 5 inhibitor; PVR = pulmonary vascular resistance.