Triple therapy for incident pulmonary arterial hypertension in Finland between 2008 and 2020. A descriptive real-world FINPAH cohort study

Abstract

Abstract Background Treatment of pulmonary arterial hypertension (PAH) with triple therapy (TriT) including phosphodiesterase type-5 inhibitors (PDE5), endothelin receptor antagonists (ERA), and prostacyclin receptor agonists (PRA) or analogues (PCA) is indicated in severe PAH. There is evidence of benefit also in intermediate-risk patients. Purpose To describe the real-world use of TriT in a contemporary cohort of Finnish PAH patients. Methods Data was collected via chart review by treating clinicians. Pulmonary hypertension (PH) patients were diagnosed between 2008–19 at the five Finnish university hospitals. Patient characteristics and clinical information were combined with mortality data from Statistics Finland. Persistence and survival were estimated using Kaplan-Meier. Results Out of 493 incident PH patients with medication history available, TriT was recorded for 41 (8%), with a median follow-up of 5.86 years (IQR: 4.12-8.72). TriT patients were predominantly women (73%), mean age 55 years (IQR 46–69) at diagnosis. 35 patients (85%) had PAH (37% iPAH, 27% PAH associated with connective tissue disease and 22% other PAH subclasses), and 6 patients (15%) had other PH types, mostly CTEPH. TriT was started at a median of 2.15 years (IQR: 0.65-3.64) after diagnosis. At the initiation of TriT, 7 patients (17%) had NYHA functional class (FC) IV, 21 (51%) had FC III, 8 (20%) had FC II. Median six-minute walking distance (6MWD) was 360 m (IQR 245-435 m, N=33). Median BNP was 328 pg/mL (IQR 190-723, N=10), and median NT-proBNP was 1082 pg/mL (IQR 745-3420, N=31). Fewer than 3 patients (<7%) were at ESC/ERS 2015 high risk. Initial PRA or PCA in TriT was iloprost (n=21, 51%), selexipag (n=12, 29%), or treprostinil (n=8, 20%). Initial ERA in TriT was macitentan (n=20, 49%), bosentan (n=11, 27%), or ambrisentan (n=10, 24%). Initial PDE5 was sildenafil (n=36, 88%) or tadalafil (n=5, 12%). Estimated persistence with TriT was 88% at 1 year and 84% at 5 years. Selexipag and iloprost were discontinued in <3 (<25% of users) and in 12 (57% of users), respectively, and 10 patients (24%) were switched to treprostinil. 6 TriT patients were listed for lung transplant after start of TriT, and 4 received a lung transplant. Six months after start of TriT, 4 patients (10%) had died and 5 (12%) had discontinued TriT. For the patients with 6 months of recorded TriT use (N=31), NT-proBNP changed by median -184 pg/mL (IQR -689 to +165, N=24), and 6MWD changed by median +20 m (IQR -3 to +35, N=22). In 8 patients (30%) FC improved within 6 months of TriT, was stable in 15 patients (56%) and worsened in 4 patients (15%). After 6 months of TriT, no patient was at high risk. Estimated overall survival was 90% (95%-CI 82-100%) at 6 months and 1 year after start of TriT. Estimated 5-year survival was 52% (95%-CI 38-72%). Conclusion(s) The study shows infrequent use but high persistence of TriT in Finnish PAH patients. TriT patients remained generally stable while on TriT.