A Bayesian network meta-analysis on the efficacy and safety of eighteen targeted drugs or drug combinations for pulmonary arterial hypertension

Figures & data

Figure 1. Flowchart for the process of screening out the included studies.

Figure 2. Network structure for all outcomes. The network plots show direct comparison of different treatments, with node size corresponding to the sample size. The number of included studies for specific direct comparison decides the thickness of solid lines.

Figure 3. Node-splitting results for outcomes. p < .05 indicates inconsistency between direct and indirect evidence. A: placebo; B: bosentan; C: ambrisentan; D: macitentan; E: sitaxsentan; F: berapost; G: treprostinil; H: epoprostenol; I: ambrisentan + tadalafil; J: vardenafil; K: tadalafil; L: sildenafil; M: sildenafil + bosentan; N: sildenafil + epoprostenol; O: iloprost + bosentan; P: bosentan + epoprostenol; Q: riociguat + sildenafil; R: riociguat; S: selexipag.

Table 1. Surface under the cumulative ranking curve (SUCRA) results for outcomes.

Treatment	6MWD change	WHOFC improvement	BDS change	CI change	mPAP change	mRAP change	PVR change	Clinical worsening	Hospitalization	Death	SAEs	Withdrawal
Placebo	0.0950	0.1247	0.0524	0.1601	0.0792	0.2807	0.2001	0.1298	0.2215	0.3068	0.5331	0.4537
Bosentan	0.5731	0.4197	0.5903	0.7154	0.6424	0.7139	0.8170	0.6550	0.5396	0.5518	0.3437	0.6639
Ambrisentan	0.5679	0.3266	0.5031	–	–	–	–	0.6130	0.4268	0.6676	–	0.6603
Macitentan	0.3047	0.8385	–	–	–	–	–	0.3159	0.4533	0.2015	0.7147	0.5359
Sitaxsentan	0.3808	0.3909	–	0.4171	0.4455	0.5105	0.0139	0.6706	0.7511	0.4933	0.5162	0.6994
Berapost	0.3678	0.2442	0.3283	0.2196	0.1880	0.4511	–	0.4688	–	0.4928	0.8179	0.1360
Treprostinil	0.4376	0.5017	0.8771	0.4501	0.1198	0.4494	0.2346	0.2369	0.2237	0.4417	0.6964	0.2723
Epoprostenol	0.6204	0.9667	–	0.6105	0.6862	0.6160	–	–	–	0.7404	0.1614	0.3889
Ambrisentan + tadalafil	0.8513	0.5071	–	–	–	–	–	0.8467	0.8411	0.5404	–	0.5432
Vardenafil	0.8172	0.3100	0.8802	0.4892	0.5631	0.5595	–	0.8312	–	0.8405	0.6851	0.9813
Tadalafil	–	0.4990	–	–	–	–	–	0.3646	0.5097	0.4045	–	–
Sildenafil	0.5991	0.7901	–	0.5518	0.4654	0.4360	0.4664	0.4411	0.6587	0.2514	0.2311	0.3664
Sildenafil + bosentan	0.7703	0.7008	–	–	–	–	–	–	–	0.3453	0.4775	0.2482
Sildenafil + epoprostenol	0.3194	–	–	–	–	–	–	–	–	0.9712	0.3505	0.6923
Iloprost + bosentan	0.7098	–	–	–	0.9490	–	0.9931	0.9034	–	0.7201	0.5958	0.6885
Bosentan + epoprostenol	0.3651	–	–	0.9900	0.9338	0.7909	–	–	–	0.4084	0.3396	0.2066
Riociguat + sildenafil	–	–	–	–	–	–	–	–	–	0.4603	0.1951	0.3393
Riciguat	0.3183	0.3799	0.2687	0.3375	0.4275	0.5838	0.5608	0.1910	0.4845	0.4999	0.6490	0.5026
Selexipag	0.4022	–	–	0.5588	–	0.1083	0.7141	0.3320	0.3899	0.1623	0.6929	0.6212

6MWD: 6 minutes walking distance; FC: functional class; BDS: Borg dyspnea score; CI: cardiac index; mPAP: mean pulmonary artery pressure; mRAP: mean right arterial pressure; PVR: pulmonary vascular resistance; SAEs: severe adverse event. The bolded value is top three SUCRA under each endpoints.

Figure 4. Heat plots of CI change, clinical worsening, hospitalization and WHO FC improvement. The area of the gray squares displays the contribution of the direct estimate in the design shown in the column to the network estimate in the design shown in the row. The colors are associated with the change in inconsistency between direct and indirect evidence. Blue colors indicate a decrease and warm colors indicate an increase (the stronger the intensity of the color, the stronger the change). A: placebo; B: bosentan; C: ambrisentan; D: macitentan; E: sitaxsentan; F: berapost; G: treprostinil; H: epoprostenol; I: ambrisentan + tadalafil; J: vardenafil; K: tadalafil; L: sildenafil; M: sildenafil + bosentan; N: sildenafil + epoprostenol; O: iloprost + bosentan; P: bosentan + epoprostenol; Q: riociguat + sildenafil; R: riociguat; S: selexipag.

Figure 5. Heat plots for SAEs, withdrawal, and death.