Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 10;14(1):e12351.
doi: 10.1002/pul2.12351. eCollection 2024 Jan.

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study

Qin-Hua Zhao  1 , Jun Chen  2 , Fa-Dong Chen  3 , Hong-Yun Ruan  4 , Wei Zhang  5 , Yan-Li Zhou  6 , Qi-Qi Wang  7 , Xiao-Ling Xu  8 , Ke-Fu Feng  9 , Jian-Zhou Guo  10 , Su-Gang Gong  1 , Rui-Feng Zhang  11 , Lan Wang  1
Affiliations

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study

Qin-Hua Zhao et al. Pulm Circ. .

Abstract

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Keywords: event; oral sequential triple combination therapy; pulmonary arterial hypertension; risk stratification; survival.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Comparison of clinical parameters before and after 6 months of treatment in the entire cohort. (a) WHO functional class (WHO‐FC); (b) 6‐min walk distance (6MWD); (c) N‐terminal fragment of probrain natriuretic peptide (NT‐proBNP); (d) The number of low risk criteria. WHO, World Health Organization.
Figure 2
Figure 2
Comparison of changes before and after 6 months of treatment in different risk groups. (a) Change of 6‐min walk distance (6MWD); (b) Change of N‐terminal fragment of probrain natriuretic peptide (NT‐proBNP); (c) Change of WHO functional class (WHO‐FC); (d) Change of pulmonary artery systolic pressure (PASP); (e) Change of left ventricular end diastolic diameter (LVEDD); (f) Change of tricuspid annular plane systolic excursion (TAPSE); (g) Change of eccentricity index (EI).
Figure 3
Figure 3
Cox regression analysis of clinical parameters and survival in the entire cohort. 6MWD, 6‐min walking distance; CO, cardiac output; EI, eccentricity index; LVEDD, left ventricular end‐diastolic dimension; LVEF, left ventricular ejection fraction; mPAP, mean pulmonary artery pressure; mPAWP, mean pulmonary artery wedge pressure; mRAP, mean right atrial pressure; PASP, pulmonary arterial systolic pressure; PE, pericardial effusion; PVR, pulmonary vascular resistance; RA area, right atrium area; RAP, right atrial pressure; RV, right ventricle; Sm, peak systolic velocity of tricuspid annulus; SVO2, mixed venous oxygen saturation; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation; WHO‐FC, World Health Organization functional classification.
Figure 4
Figure 4
The 6‐month event‐free survival and 2‐year survival of patients undergoing oral triple combination therapy. (a) Six‐month event‐free survival in the entire corhot; (b) 2‐year survival rates in the entire corhot; (c) Comparison of the 6‐month event‐free survival in different risk groups; (d) Comparison of 2‐year survival rates in different risk groups.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Leber L, Beaudet A, Muller A. Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review. Pulm Circ. 2021;11(1):1–12. - PMC - PubMed
    1. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano‐Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke‐Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S, Schwerzmann M, Dinh‐Xuan AT, Bush A, Abdelhamid M, Aboyans V, Arbustini E, Asteggiano R, Barberà JA, Beghetti M, Čelutkienė J, Cikes M, Condliffe R, de Man F, Falk V, Fauchier L, Gaine S, Galié N, Gin‐Sing W, Granton J, Grünig E, Hassoun PM, Hellemons M, Jaarsma T, Kjellström B, Klok FA, Konradi A, Koskinas KC, Kotecha D, Lang I, Lewis BS, Linhart A, Lip GYH, Løchen ML, Mathioudakis AG, Mindham R, Moledina S, Naeije R, Nielsen JC, Olschewski H, Opitz I, Petersen SE, Prescott E, Rakisheva A, Reis A, Ristić AD, Roche N, Rodrigues R, Selton‐Suty C, Souza R, Swift AJ, Touyz RM, Ulrich S, Wilkins MR, Wort SJ. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618–3731. - PubMed
    1. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long‐term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL registry. Chest. 2012;142(2):448–456. - PubMed
    1. Gall H, Felix JF, Schneck FK, Milger K, Sommer N, Voswinckel R, Franco OH, Hofman A, Schermuly RT, Weissmann N, Grimminger F, Seeger W, Ghofrani HA. The Giessen pulmonary hypertension registry: survival in pulmonary hypertension subgroups. J Heart Lung Transplant. 2017;36(9):957–967. - PubMed
    1. D'Alto M, Badagliacca R, Argiento P, Romeo E, Farro A, Papa S, Sarubbi B, Russo MG, Vizza CD, Golino P, Naeije R. Risk reduction and right heart reverse remodeling by upfront triple combination therapy in pulmonary arterial hypertension. Chest. 2020;157(2):376–383. - PubMed