Don't miss the launch of our new #accredited feed for 🆓 CE/#CME on #obesity management! A worthy companion to @pulmmed_ce!.Launched today from @obesity_ce. FOLLOW US NOW!. XOXO, @academiccme

RT @jeanlucvachiery: @ISHLT @AssociationWsph @sbonnet2.

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44) And WHEW!! That was like TEN #6MWT because you just earned a full HOUR of 🆓 CE/#CME! Claim your certificate now at and then FOLLOW US for more expert-authored #MedEd! Thanks to outstanding faculty @jeanlucvachiery for joining our @pulmmed_ce team!.

43) That’s a wrap! 🔑 learnings:.🫁 NO-PDE5i-sGCs important in #PAH.🫁 #PDE5i are widely used, especially in initial combo tx.🫁 #sGCs have a different mode of action, though lumped in the same pathway.🫁 switching from PDE5i to sGCs should be considered in pts not at goal.

42c) Once the “ideal” dose has been established, the second cohort of 286 patients will be initiated (placebo-controlled, 2 arms) with changes in #6MWD at W12 being the primary EP. The whole cohort will be eventually analyzed for efficacy and safety across a broad range of EP.

41c) The first cohort of 164 patients will be randomized in 4 arms (3 doses vs placebo) with #PVR at 12 weeks as primary endpoint.

41b) The efficacy and safety of #MK_5475 in #PAH is being tested in the Ph 2/3 #INSIGNIA_PAH study. In an adaptative design, a total of 450 patients with persistent symptoms with be included in sequence.

41a) What does the future hold? Novel tx for #PAH aims to explore 🆕 pathways but also ⬆️ safety/tolerability profiles of currently available compounds (big focus on inhaled therapies!). #MK_5475 is a small molecule designed for inhaled delivery via a dry-powder inhaler device.

40) Standing still is not an option! Patients deserve treatment escalation or switch (do not combine #PDE5i with #sGCs!). Of note, this is the perfect time to engage in a discussion on participation in clinical trials!

39) Next step requires a reassessment, treatment decisions being based on a 4-strata evaluations. What are the options if low risk at 3-6 months is not achieved ?.a. Wait and see.b. oral prostanoids receptor agonist.c. IV prostanoids and consider transplantation.d. Not a.

38c) What about high-risk patients? Well, they should be on parenteral #prostacyclin, together with oral combination therapy with #ERA and #PDE5i

38b) But which #PDE5i? The wealth of evidence is in favor of #tadalafil (from large trials #PHIRST, #AMBITION, #TRITON, open label #OPTIMA)

38a) Let’s focus on initial tx for pts without comorbidities. Based on the revised table, it is recommended that patients in low/intermediate risk receive initial combination therapy with an #ERA and a #PDE5i

37) Let’s wrap up and see what the #ESC/#ERS GL say about the NO-#PDE5i-#sGC pathway…here is the “strategic” treatment algorithm. Evidence has been shown for #iPAH, #hPAH and #PAH associated with drugs/toxins and #CTD.

36) Two long-term registries confirmed the safety of #riociguat for the treatment of #PAH: #CAPTURE (switch from #PDE5i to rio) and #EXPERT (all indications).🔓 🔓

35) Thus, the recommendation to switch a #PDE5i to #riociguat is less strong in the guidelines than the option to add #selexipag. Adding #selexipag is supported by the #GRIPHON #RCT.🔓

34) Additionally, the benefit of switching to #riociguat seemed to be greater in patients on #sildenafil at baseline, rather than those on #tadalafil

33) In #REPLACE, patients were not blinded to whether they switched to #riociguat or continued on a #PDE5i. This could have influenced how @WHO functional class was reported or influenced performance on the #6MWD.

32) Switching a #PDE5i to #riociguat was studied in the #REPLACE trial. REPLACE was an open label #RCT: those switching to riociguat more often achieved the ‘multi-component improvement’ endpoint (improvement in 2/3 of #NYHA, #6MWD & #NTproBNP).