The impact of delayed treatment on 6-minute walk distance test in patients with pulmonary arterial hypertension: A meta-analysis

Abstract

A short-term delay in PAH targeted therapy may adversely affect functional capacity in patients with PAH. This meta-analysis provides some insight as to whether earlier treatment would benefit stable patients with PAH.

POINT: Should Initial Combination Therapy Be the Standard of Care in Pulmonary Arterial Hypertension? Yes

“…A meta-analysis of six PAH short-term RCTs showed that the placebo group never "caught up" to the active group in terms of 6-min walk distance following open label therapy. 17 This suggests that a treatment delay of 12 to 16 weeks may have a long-term effect on functional capacity and outcome.…”

Evidence synthesis in pulmonary arterial hypertension: a systematic review and critical appraisal

“…The publication year ranged between 2007 [ 43 ] and 2020 [ 39 , 41 , 48 , 67 ] with most studies published in recent years. MAs were conducted in 35 studies [ 17 , 19 , 20 , 22 , 23 , 26 – 29 , 31 , 35 – 41 , 43 – 47 , 49 – 51 , 53 , 56 , 58 – 60 , 63 – 66 , 69 ], NMAs in 15 studies [ 18 , 21 , 24 , 25 , 30 , 32 , 33 , 42 , 48 , 52 , 54 , 57 , 61 , 62 , 67 ], both NMA and MA in one study [ 55 ], and MA and disproportionality analysis in one study [ 34 ]. Of 52 studies, 47 evaluated the impact of PAH interventions in patients with PAH and PAH subgroups (based on aetiology, e.g.…”

“…Further critical appraisal performed based on input from clinical experts. Vizza 2018 [ 56 ] Patients with PAH MA 6 Oral bosentan, oral ambrisentan, oral riociguat, oral tadalafil and oral/inhaled treprostinil 6MWD Not reported Wang 2018 e [ 57 ] Patients with PAH NMA 45 Oral ERAs (ambrisentan, bosentan, macitentan, sitaxsentan), oral PDE5Is (sildenafil, tadalafil, vardenafil d ), prostanoids (IV epoprostenol, oral/IV/inhaled/SC treprostinil, inhaled iloprost, oral beraprost), sGCSs (oral riociguat), sPRA (oral selexipag) 6MWD, WHO FC, BDI, cardiac index, PAP, RAP, PVR, clinical worsening, hospitalization, death, SAEs, and withdrawal Not reported Wei 2016 [ 58 ] Patients with different diseases including PAH MA 24 Oral ERAs (bosentan, ambrisentan and macitentan); EU authorised AEs Cochrane’s risk of bias and GRADE for evidence Xing 2011 [ 59 ] Patients with PAH (including idiopathic PAH, familial PAH, as well as CTD-associated PAH, pulmonary shut, portal hypertension, HIV infection and thyroid disease) MA 10 Prostanoids (IV epoprostenol, IV/SC treprostinil, oral beraprost and inhaled iloprost) 6MWD, BDI, cardiac index, mean PAP, PVR, mortality, clinical worsening and AEs Jadad scores Zhang 2015 [ 60 ] Patients with PAH MA 21 Oral treatments (ambrisentan, bosentan, macitentan, sitaxentan, sildenafil, tadalafil, riociguat, beraprost, epoprostenol, treprostinil, terbogrel d and imatinib d ) CCW or at least all-cause mortality Cochrane’s risk of bias Zhang 2016 [ 61 ] Patients with PAH NMA 14 Prostanoids (IV epoprostenol, inhaled/IV/oral/SC treprostinil, oral beraprost and inhaled iloprost) 6MWD, mortality, Functional Class, and discontinuation Not reported Zhang 2019 [ 62 ] Patients with PAH NMA 10 Oral ERAs (bosentan, ambrisentan, macitentan) Safety outcomes: abnormal li...…”

“…MEDLINE, Embase, CENTRAL [18,29,32,34,35,44,45,52,53,68]. Several studies did not provide details of the search strategy [18-21, 24-26, 29, 31, 32, 35, 36, 39, 40, 44-46, 49, 50, 52-55, 59-61, 63, 67, 68] and one study did not provide any details on the search strategy and searched databases [58]. Although Badiani 2015 reported that prostanoids with IV/inhaled/SC ROA were considered for evaluation, trials on prostanoids with these ROAs were not included in the analysis.…”

Incremental Shuttle Walking Test Distance Is Reduced in Patients With Pulmonary Hypertension in World Health Organisation Functional Class I

“…Despite advances in treatment, pulmonary hypertension (PH) remains a progressive life-limiting disease ( 1 ). Studies have suggested that earlier intervention results in better outcomes ( 2 , 3 ). However, patients are usually diagnosed when the disease is advanced ( 4 , 5 ) and consequently there is interest in developing strategies to enable earlier diagnosis ( 6 ).…”