2) This program is supported by an unrestricted educational grant from Bayer. Statement of accreditation & faculty disclosures at https://t.co/rrev7r5sxk. Prior programs, still available for FREE CE/#CME, are at https://t.co/DZztOofO5J.
— cardio-met (@cardiomet_CE) August 15, 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.#pulmtwitter @MedTweetorials #FOAMcc
— cardio-met (@cardiomet_CE) August 15, 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/araQze2GKw
— cardio-met (@cardiomet_CE) August 15, 2023
7b) The answer is D. In a newly diagnosed pt w/#PAH your initial tx strategy should factor in #1 Risk & #2 comorbidities.
— cardio-met (@cardiomet_CE) August 15, 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:
— cardio-met (@cardiomet_CE) August 15, 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 within PAH, though a new 4th pathway is on the horizon (more on this later). pic.twitter.com/Yq9c0NVhah
— cardio-met (@cardiomet_CE) August 15, 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/e3Uek4tSss
— cardio-met (@cardiomet_CE) August 15, 2023
13b) Based on the #AMBITION trial, #ambrisentan + #tadalafil has the strongest data but other PDE5i+ERA combinations can be used.https://t.co/MF6M6lEiXB pic.twitter.com/dZU3smG1Oz
— cardio-met (@cardiomet_CE) August 15, 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)
— cardio-met (@cardiomet_CE) August 15, 2023
🔓 https://t.co/4gky55JdPz
🔓 https://t.co/tadcPH03mi pic.twitter.com/pTCRQrnKos
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.
— cardio-met (@cardiomet_CE) August 15, 2023
🔓 https://t.co/jyDLUscQZI pic.twitter.com/oakd9gfwbA
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.
— cardio-met (@cardiomet_CE) August 15, 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.
— cardio-met (@cardiomet_CE) August 16, 2023
🫁 Let’s go back to the 2022 @escardio @EuroRespSoc treatment algorithm for #PAHhttps://t.co/AeXg1QqVlM pic.twitter.com/IOl9jxRPsB
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/D1XcC5vRMf pic.twitter.com/6PRErBEomZ
— cardio-met (@cardiomet_CE) August 16, 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/dtJX1JFEy1 pic.twitter.com/cb87rCww3n
— cardio-met (@cardiomet_CE) August 16, 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?
— cardio-met (@cardiomet_CE) August 16, 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/00ps8yg6x7 pic.twitter.com/F0EANiXD6b
— cardio-met (@cardiomet_CE) August 16, 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/UIdFtvu5CI
— cardio-met (@cardiomet_CE) August 16, 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).
— cardio-met (@cardiomet_CE) August 16, 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.
— cardio-met (@cardiomet_CE) August 16, 2023
🔓 https://t.co/4vFMHffKwd
35b) Answer: C. These decisions can be complex. The #guidelines suggest adding a parenteral #prostacyclin (e.g. #epoprostenol i.v., or #treprostinili.v./s.c.). For those who aren’t eligible for these therapies, #LungTransplant referral is also appropriate
— cardio-met (@cardiomet_CE) August 16, 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.
— cardio-met (@cardiomet_CE) August 16, 2023
🔓 https://t.co/pofFYpK3ZK pic.twitter.com/tcv4vuJvbr
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/qqyftFTrzG pic.twitter.com/ELcSDIOEBr
— cardio-met (@cardiomet_CE) August 16, 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/rnPjO5pgMw
— cardio-met (@cardiomet_CE) August 16, 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!
— cardio-met (@cardiomet_CE) August 16, 2023
Shout outs to @SarahMedrek @TamCardio @kurt_prins @LungTxptMD @thenappanMD @JournalClubPH @PGeorgeMD @mdlizs pic.twitter.com/OZJ1ysg7MC
44b) So you have alot of learning but just a few 🖱️ clicks away from bright, shiny, and FREE CE/#CME certificate!
— cardio-met (@cardiomet_CE) August 17, 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/GCJUYsX4xy
— cardio-met (@cardiomet_CE) August 17, 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.
— cardio-met (@cardiomet_CE) August 17, 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.
— cardio-met (@cardiomet_CE) August 17, 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/wp6DnQ8fsD pic.twitter.com/OVrqasvqKx
— cardio-met (@cardiomet_CE) August 17, 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/VeGyqANzsN pic.twitter.com/Si629Dcd1r
— cardio-met (@cardiomet_CE) August 17, 2023
54b) Answer: c, #Bosentan. The #BREATHE_5 trial showed that bosentan improved PVR and #6MWD: 🔓 https://t.co/pTX0TGnhfz
— cardio-met (@cardiomet_CE) August 17, 2023
🔃 Conversely the #MAESTRO trial found no effect of #macitentan on 6MWD: 🔓 https://t.co/pTX0TGnhfz pic.twitter.com/yAVqYbDkcX
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.
— cardio-met (@cardiomet_CE) August 17, 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.
— cardio-met (@cardiomet_CE) August 17, 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/CSZQjQ3eRC and claim your 🆓 0.75hr CE/#CME! This is @AlbertaPHdoc pic.twitter.com/03DDq9COvM
— cardio-met (@cardiomet_CE) August 17, 2023