2) This program is supported by an unrestricted educational grant from Bayer. Statement of accreditation & faculty disclosures at https://t.co/0EkFYk4TZx. Prior programs, still available for FREE CE/#CME, are at https://t.co/Z8M0L9k0hD.
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
4) The main consequence of #PAH is increased right ventricular (#RV) afterload, which can lead to right 🫀failure & ☠️. Fortunately, effective treatment options for PAH have improved outcomes.@MedTweetorials #FOAMcc @PulmCCM @PHAssociation
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
6) The diagnosis of #PAH requires a right heart catheterization #RHC demonstrating a mean pulmonary artery pressure (mPAP) >20 mmHg, a wedge pressure ≤ 15 mmHg, & #PVR > 2 Wood units. Also, other causes of PH (i.e. left heart disease, lung disease, #CTEPH need to be excluded) pic.twitter.com/9N1wD7Rygq
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
7b) The answer is D. In a newly diagnosed pt w/#PAH your initial tx strategy should factor in #1 Risk & #2 comorbidities.
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
8) The most important 1st tx decision depends on whether a pt has an acute vasoreactive response to inhaled nitric oxide #NO. This is defined as all 3 of:
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
i. ⬇️in mPAP by at least 10 mmHg
ii. mPAP reaches an absolute value of ≤40 mmHg
iii. Cardiac output remains stable or ⬆️
10) For #PAH patients without acute #vasoreactivity, there are several approved treatments targeting 3 pathways with in PAH, though a new 4th pathway is on the horizon (more on this later). pic.twitter.com/vYsMEzl6bL
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
12) The 2022 #PH Guidelines treatment algorithm is below. You can see that the first factor to consider is #cardiopulmonary #comorbidity. pic.twitter.com/09xn3AyAwB
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
13b) Based on the #AMBITION trial, #ambrisentan + #tadalafil has the strongest data but other #PDE5i + #ERA combinations can be used.https://t.co/zR7VQ7JTfO
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
14b) This recommendation is based on non-randomized studies that show marked improvement with triple therapy compared to other regimens (acknowledging the biases that come with such designs)
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
🔓 https://t.co/WlYsPKpTon
🔓 https://t.co/69y8zHGRQt pic.twitter.com/ZgRIGhpob7
16) In the #AMBITION trial, pts with risk factors for #heartfailure with #HFpEF were older, had ⬇️ benefit with combination therapy (Ex-Primary analysis set), and ⬆️ rates of drug discontinuation vs those without risk factors.
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
🔓 https://t.co/ZxScLNZcpl pic.twitter.com/nbb62V8dV7
18) Let's pause there and catch our breath. Return tomorrow for more education on Guidelines and Recent Data: Developing Optimal Treatment Plans for Patients with #PAH.
— pulmmed_ce (@Pulmmed_CE) August 1, 2023
👏 to @jeanlucvachiery @SteveMathaiMD @LucillaPiccari @rjbernardoMD @navneetsinghmd @JournalClubPH
20) In today's 🧵we will discuss how to escalate or modify therapy for patients not meeting treatment goals.
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
🫁 Let’s go back to the 2022 @escardio @EuroRespSoc treatment algorithm for #PAHhttps://t.co/OeFW3KbD1Y pic.twitter.com/vWJOe34f0o
22) The European 4-strata risk assessment uses 3 variables: Functional Class, 6-minute walk distance, & #BNP/NT-proBNP. This approach is supported by #COMPERA & French registry studies showing ⬆️risk assessment during follow-up using this 4-strata method.https://t.co/9Z5hsf1rQA pic.twitter.com/PkQIUiDM6N
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
24) An important digression here. While risk scores are associated with survival in #registry-based studies, a recent study of 3 large #RCTs showed that, in fact, risk scores are not adequate surrogates for clinical worsening or mortality.https://t.co/vFS4F7ZOL6 pic.twitter.com/a1ZGpe2UnG
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
26) Back to the Rx algorithm! If your patient is in the intermediate-low risk group, the guidelines suggest two options. Which would you choose?
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
a. Replace the #PDE5i with #riociguat
b. Add #selexipag
28) 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)https://t.co/bzkbeBnzNM pic.twitter.com/PVhxG5b99n
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
30) Additionally, the benefit of switching to #riociguat seemed to be greater in patients on #sildenafil at baseline, rather than those on #tadalafil pic.twitter.com/t93Ahb28T2
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
32) In #GRIPHON, 1156 patients were randomized to #selexipag or placebo. Selexipag reduced the primary endpoint composite of death or complication of #PAH (HR 0.60, 95%CI 0.46-0.78).
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
34) Another option is to ➕oral #treprostinil, if available. It is not approved in Europe, so not part of the European guideline recs. The addition of oral treprostinil to background monotherapy ⬇️clinical worsening by 26% in the #FREEDOM_EV trial.
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
🔓 https://t.co/v18TX65m52
35b) Answer: C. These decisions can be complex. The #guidelines suggest adding a parenteral #prostacyclin (e.g. #epoprostenol i.v., or #treprostinil i.v./s.c.). For those who aren’t eligible for these therapies, #LungTransplant referral is also appropriate
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
37) One study of 126 patients on combination therapy found that adding i.v. #treprostinil improved about 1 in 5 patients who were intermediate or high risk to low risk. Those who didn’t reach low risk had a 9-fold higher mortality.
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
🔓 https://t.co/7NH2i7v7OK pic.twitter.com/mETUhjWchC
39) A new option for #PAH tx is likely also on the horizon. #Sotatercept is the 1st biologic tx for PAH. It is not yet approved for use by regulatory agencies, but the recent phase 3 #STELLAR trial convincingly demonstrated efficacy of sotatercept in PAH. https://t.co/6CUQcqnUhA pic.twitter.com/vIs8Ve5Dp7
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
41) In the STELLAR trial, #sotatercept also improved multiple secondary endpoints including time to death or non-fatal clinical worsening (HR 0.16, 95% CI, 0.08 to 0.35). pic.twitter.com/rHQvUUB3Oe
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
43) That wraps up this section. Tune in for the next 🧵right here TOMORROW about optimizing therapy – tailoring to #PAH etiology, and a link to your 🆓 CE/#CME!
— pulmmed_ce (@Pulmmed_CE) August 2, 2023
Shout outs to @SarahMedrek @TamCardio @kurt_prins @LungTxptMD @thenappanMD @JournalClubPH @PGeorgeMD @mdlizs pic.twitter.com/TWXzqlcFkx
44b) So you have alot of learning but just a few 🖱️ clicks away from bright, shiny, and FREE CE/#CME certificate!
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
Tip o' the 🎩to @viniviodjperez @RogerAlvarezDO @navneetsinghmd @heresi_gustavo @Arunachalam_md
46) Let’s consider the etiology of #PAH and how it can influence tx decisions. Patients with #portopulmonary hypertension (#PoPH) have otherwise unexplained pre-capillary pulmonary hypertension and portal hypertension. pic.twitter.com/46OQQOiG5t
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
48) #PDE5 inhibitors, #ERAs, and PDE5i+ERA combinations are often used in #PoPH. The guidelines suggest starting with monotherapy then sequential combination therapy based on response, liver disease, and liver transplant indications.
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
49b) Answer: A, #Macitentan. #Bosentan was the first #ERA approved for #PAH but has hepatotoxicity occurs in 10-15% of patients. #Sitaxentan was withdrawn from the market due to hepatoxicity concerns. There are limited data with #ambrisentan in PoPH.
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
51) What are treatment goals in #PoPH? This depends on whether liver transplant is being pursued. #PAH improves after liver Tx in some patients with PoPH but this is not universal and PoPH is not considered an indication for liver Tx. https://t.co/AE6zcCmxta pic.twitter.com/gLX8X2lbKE
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
53) What about other causes of #PAH? Should the treatment approach differ for patients with PAH due to congenital 🫀 disease (#CHD)? 🔓https://t.co/70TObM2Mw4 pic.twitter.com/bS9u7JfqyX
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
54b) Answer: C, #Bosentan. The #BREATHE_5 trial showed that bosentan improved PVR and #6MWD: 🔓 https://t.co/A4pWHdpmnh
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
🔃 Conversely the #MAESTRO trial found no effect of #macitentan on 6MWD: 🔓 https://t.co/A4pWHdpmnh pic.twitter.com/Ya4hTfpaEz
56a) Another ❓ that comes up in #PAH due to uncorrected #CHDs: Should you close the defect? Shunt closure should only be considered in pts with systemic-to-pulmonary shunting WITHOUT significantly ⬆️PVR.
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
57) Well, that wraps up part 3. We have discussed the recent @EuroRespSoc and @escardio #PulmonaryHypertension guidelines which can help guide tailored therapy to your patients with #PAH.
— pulmmed_ce (@Pulmmed_CE) August 3, 2023
59) So THANK YOU for joining us! FOLLOW @pulmmed_ce for more expert-led #MedEd in 🫁 medicine! And for now, reward yourself! Go to https://t.co/MGiXKRNYbp and claim your 🆓 0.75hr CE/#CME! This is @AlbertaPHdoc pic.twitter.com/ZWgQQh5iHk
— pulmmed_ce (@Pulmmed_CE) August 3, 2023