Does combination therapy work in chronic thromboembolic pulmonary hypertension?

OBJECTIVE: The current experience with combination therapy in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. We present the first survival results up to 5 years for dual combination therapy versus monotherapy in CTEPH. METHODS: All consecutive, non-operated CTEPH or residual PH after pulmonary endarterectomy patients treated with PH-specific medical therapy between January 2002 and November 2019 were included. We report and compare survival between monotherapy and (upfront or sequential) dual combination therapy until five years after medication initiation. RESULTS: In total, 183 patients (mean age 65 ± 14 years, 60% female, 66% WHO FC III/IV, 86% non-operated) were included, of which 83 patients received monotherapy and 100 patients received dual combination therapy. At baseline, patients receiving combination therapy had a higher NT-proBNP (p = 0.02) mean pulmonary artery pressure (p = 0.0001) and pulmonary vascular resistance (p = 0.02), while cardiac index was lower (p = 0.03). Total follow-up duration was 3.3 ± 1.8 years, during which 31 (17%) patients died. Estimated 1-, 3- and 5-year survival for monotherapy were 99%, 92% and 79%, respectively. For combination therapy percentages were 98%, 89% and 70%, respectively. Survival did not significantly differ between both groups (p = 0.22). CONCLUSION: Survival up to 5 years for patients treated with combination therapy, regardless of the combination strategy, was similar as patients with monotherapy, despite worse clinical and haemodynamic baseline characteristics.

Long-term real world clinical outcomes of macitentan therapy in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Macitentan treatment for chronic thromboembolic pulmonary hypertension (CTEPH) in the routine clinical setting is increasing. However, 'real world' macitentan experience is scarce and is needed to differentiate from controlled clinical trial settings. OBJECTIVE: We describe our outcomes and clinical 'real world' experience of macitentan mono- and combination therapy with riociguat or sildenafil in CTEPH. METHODS: We included all consecutive CTEPH patients, either non-operated or with residual PH after pulmonary endarterectomy (PEA), treated with macitentan in the St. Antonius hospital in Nieuwegein, the Netherlands, between 01-2014 and 11-2019. We describe clinical outcomes and adverse events (AEs) until 2 years after macitentan initiation. RESULTS: In total 73 CTEPH patients on macitentan were included, of which 18 patients were clinically inoperable (n = 7 declined PEA, n = 11 nonacceptable risk-benefit) and 55 had technically inoperable CTEPH (n = 48)/residual PH (n = 7). Clinically inoperable patients (mean age 72.4 ± 10.2 years, 61% female, 28% macitentan monotherapy, observation period 2.0 (1.9-2.0) years) had a survival of 100% and clinical worsening (CW)-free survival of 88% at 2-year follow-up respectively, with a significant increased 6-min walking distance (6MWD). Technically inoperable/residual PH patients (mean age 62.1 ± 14.1 years, 60% female, 27% macitentan monotherapy, observation period 2.0 (1.0-2.0) years) had a 2-year survival and CW-free survival of 86% and 68% respectively, with significant improved 6MWD and NT-proBNP. Nonsevere AEs were reported in 30% of all patients. CONCLUSION: Macitentan mono- and combination therapy in non-operated CTEPH and residual PH is safe and improves clinical outcomes till 2-year follow-up.

Safety and efficacy of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension in the Netherlands.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an emerging treatment in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease (CTED). We describe the first safety and efficacy results of BPA in the Netherlands. METHODS: We selected all consecutive patients with inoperable CTEPH and CTED accepted for BPA treatment who had a six-month follow-up in the St. Antonius Hospital in Nieuwegein and the Amsterdam University Medical Center (UMC) in Amsterdam. Functional class (FC), N­terminal pro-brain natriuretic peptide (NT-proBNP), 6­minute walking test distance (6MWD) and right-sided heart catheterisation were performed at baseline and six months after last BPA. Complications for each BPA procedure were noted. RESULTS: A hundred and seventy-two BPA procedures were performed in 38 patients (61% female, mean age 65 ± 15 years). Significant improvements six months after BPA treatment were observed for functional class (63% FC I/II to 90% FC I/II, p = 0.014), mean pulmonary artery pressure (-8.9 mm Hg, p = 0.0001), pulmonary vascular resistance (-2.8 Woods Units (WU), p = 0.0001), right atrial pressure (-2.0 mm Hg, p = 0.006), stroke volume index (+5.7 ml/m2, p = 0.009) and 6MWD (+48m, p = 0.007). Non-severe complications occurred in 20 (12%) procedures. CONCLUSIONS: BPA performed in a CTEPH expert centre is an effective and safe treatment in patients with inoperable CTEPH.

Bosentan or Macitentan Therapy in Chronic Thromboembolic Pulmonary Hypertension?

OBJECTIVE: Research comparing bosentan and macitentan in chronic thromboembolic pulmonary hypertension (CTEPH) is scarce, although macitentan might have superior pharmacologic properties. We present the first real-world, 2-year follow-up results and compare clinical outcomes of both drugs in CTEPH. METHODS: All consecutive, technical inoperable or residual CTEPH patients receiving bosentan or macitentan, diagnosed in our multidisciplinary team between January 2003 and January 2019, were included. We report and compare survival, clinical worsening (CW), adverse events, WHO FC, NT-proBNP and 6-min walking test (6MWT) until 2 years after medication initiation. RESULTS: In total, 112 patients receiving bosentan or macitentan (58% female, mean age 62 ± 14 years, 68% WHO FC III/IV, 51% bosentan) could be included. Mean treatment duration was 1.9 ± 0.4 years for bosentan and 1.2 ± 0.6 years for macitentan. Two-year survival rate was 91% for bosentan and 80% for macitentan (HR mortality macitentan 1.85 [0.56-6.10], p = 0.31). Two-year CW-free survival was 81% and 58%, respectively (HR CW macitentan 2.16 [0.962-4.87], p = 0.06). Right atrial pressure, cardiac output (for mortality alone) and 6MWT lowest saturation were multivariate predictors at baseline. Overall adverse event rates were comparable and WHO FC, NT-proBNP and 6MWT distance improved similar for both drugs till 2-year follow-up. CONCLUSION: CTEPH patients receiving bosentan or macitentan have improved clinical outcomes till 2-year follow-up, without significant differences in outcomes between both therapies.

Long-term clinical value and outcome of riociguat in chronic thromboembolic pulmonary hypertension.

BACKGROUND: To improve clinical outcome, patients with inoperable and residual chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with riociguat. The aim of this study is to explore long-term outcomes and to compare our 'real world' data with previous research. METHODS: We included all consecutive patients with technical inoperable and residual CTEPH, in whom riociguat therapy was initiated from January 2014 onwards, with patients followed till January 2019. Survival, clinical worsening (CW), functional class (FC), N-terminal pro brain natriuretic peptide (NT-proBNP) and 6-minute walking distance (6MWD) were described yearly after riociguat initiation. RESULTS: Thirty-six patients (50% female, mean age 64.9 ±â€¯12.1 years, 54% WHO FC III/IV and 6MWD 337 ±â€¯138 m could be included, with a mean follow-up of 2.3 ±â€¯1.2 years. Survival and CW-free survival three years after initiation of riociguat were 94% and 78%, respectively. The 6MWD per 10 m at baseline was a significant predictor (HR 0.90 [0.83-0.97], p = 0.009) for CW. At three years follow-up the WHO FC and 6MWD improved and NT-proBNP decreased compared to baseline. CONCLUSION: Our study confirms that riociguat is an effective treatment in patients with technical inoperable and residual CTEPH at long-term follow-up. Although our results are consistent with previous studies, more 'real world' research is necessary to confirm long-term results.