Эффективность интермиттирующего режима ингаляционного илопроста при неоперабельной хронической тромбоэмболической легочной гипертензии
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Background : Specific pulmonary arterial hypertension (PAH) drug therapy may play a role in chronic thromboembolic pulmonary hypertension (CTEPH) patients, if they are not considered candidates for surgery. Given the limited number of approved for CTEPH specific PAH treatments, reliable long-term data are necessary on the effects of medical therapies in patients with CTEPH. We aimed to evaluate the efficacy and safety of i ntermittent inhaled iloprost in inoperable CTEPH. Methods : 22 inoperable CTEPH patients [aged (Me [25%; 75%]) 48,3 [38,4; 59,5] years; 63.6% females; 9.1% WHO functional class (FC) IV, 72.7% WHO-FC III, 18.2% WHO-FC II; 6-minute walking test (6-MWT) distance 348 [145; 443] m; mean pulmonary artery pressure (PAPm) 41.8 [29.3; 52.8] mmHg; tricuspid annular plane systolic excursion (TAPSE) 16.3 [14.5; 18.2] mm; plasma NT-proBNP 853.8 [562.2; 1124.2] pg/mL] 3–6 months after acute pulmonary embolism were randomized 1:1 to receive either standard therapy with adjusted-dose vitamin K antagonists and, if indicated – oxygen and diuretics or inhaled iloprost 5.0 µg/inhalation 4 times a day for 2 weeks every 3 months repetitive for 2 years added to conventional treatment. Efficacy endpoints included changes from baseline in 6-MWT, WHO-FC, echo-parameters, inflammatory markers, time to clinical worsening, and all-cause mortality. Results : At baseline (prior to therapy), there were no significant differences between iloprost and control groups. Levels of C-reactive protein and the cytokines interleukin (IL)-1b, IL-6, IL-8, γ-IF and TNF-α were increased. At month 24, patients receiving inhaled iloprost had a mean 6-MWT distance increase of 215 m (p<0.001); control patients had a mean increase in 6-MWT of 137 m (p<0.01), with a control-adjusted difference of +78 m (p=0.03). WHO-FC improved by two classes in 63.6% of iloprost vs. 0 of controls (p=0.028), by one class in 36.4% vs. 30% (p=0.091), remained the same in 0 vs. 70% (p=0.018), respectively. I nhaled iloprost delayed the time to clinical worsening (p=0.0064). Improvements were noted in control-adjusted changes in ePASP (–18.6 mmHg; p=0.0065), TAPSE (+2.4 mm; p=0.028) and plasma NT-proBNP (–256.9 pg/mL; p<0.01). Inflammatory markers levels significantly decreased in the iloprost group, while they remained unchanged in the controls. Combination therapy with inhaled iloprost was well tolerated. One patient died in the control group (p=0.093). Conclusion : Long-term i ntermittent inhaled iloprost for patients with inoperable CTEPH may improve symptom status, haemodynamics , and anti-inflammatory status.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.