2) This program for #healthcare providers is supported by an unrestricted educational grant from Bayer. Statement of accreditation & faculty disclosures at https://t.co/gvXca4G9Xm. Prior programs, still available for FREE CE/#CME, are at https://t.co/9HIu7bdHQV.
— cardio-met (@cardiomet_CE) January 3, 2024
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) January 3, 2024
6) The pathobiology of #PAH involves several mechanisms contributing to vascular remodeling: 1) a dysfunctional pulmonary #endothelium 2) a dysfunctional vascular smooth muscle 3) persistent #inflammation and immune dysregulation
— cardio-met (@cardiomet_CE) January 3, 2024
🔓 https://t.co/aozPev5MyL pic.twitter.com/u4pH4vHh4x
7b) The answer is D. Several drugs are approved worldwide under each category…but it is not as simple as it looked!
— cardio-met (@cardiomet_CE) January 3, 2024
7d) The correct answer is b. (c. is acceptable, thank you for being honest!). This is the whole purpose of this #tweetorial. pic.twitter.com/ZYwOh1e0Sp
— cardio-met (@cardiomet_CE) January 3, 2024
9) Let’s have a closer look on the NO-sGC-cGMP pathway in PH, shall we? The next illustration will be discussed in more detail.
— cardio-met (@cardiomet_CE) January 3, 2024
🔓 https://t.co/3GfcJrOkX6 pic.twitter.com/6vLhPht3l1
11) Although the total #sGC expression is ⬆️, alteration of the redox state of sGC through oxidative stress may lead to ⬇️ levels of the NO-sensitive form of sGC. pic.twitter.com/UFTU8vt4AD
— cardio-met (@cardiomet_CE) January 3, 2024
13) ⬆️ NO level can be accomplished by inhalation of NO. In #PAH, this option is critical to identify “responders” to acute #vasoreactivity testing who will receive calcium channel blockers #CCB.
— cardio-met (@cardiomet_CE) January 3, 2024
14b) #Sildenafil and #tadalafil are the two approved #PDE5i for the treatment of #PAH
— cardio-met (@cardiomet_CE) January 3, 2024
15b) #Riociguat is the only #sGC stimulator approved for the treatment of #PAH
— cardio-met (@cardiomet_CE) January 3, 2024
17a) A quick refresher…in #PAH, NO is primarily used in the following:
— cardio-met (@cardiomet_CE) January 3, 2024
a. chronically, as a treatment of PAH
b. acutely, to treat PH crisis
c. acutely to identify “responders” in idiopathic, drug-induced or heritable PAH
d. none of the above
17c) When a responder is identified, chronic therapy with a #CCB is recommended. Now…should such patient be reevaluated?—the answer is ABSOLUTELY YES.
— cardio-met (@cardiomet_CE) January 3, 2024
See #guidelines at 🔓https://t.co/AeXg1QqVlM if unsure! pic.twitter.com/RfbPGJ8DPx
19a) The combo of #sildenafil with #epoprostenol in the #PACES trial is sometimes forgotten. 267 PAH patients already on epo received 16W sild vs placebo (up to 80mg) resulting in a #6MWD placebo-adjusted increase of 28.8 meters (95% CI, 13.9-43.8 meters)https://t.co/k23W1KKqKa pic.twitter.com/5873SvuMvt
— cardio-met (@cardiomet_CE) January 3, 2024
20a) Then there was the #AMBITION trial: initial combo tx (#PDE5i + #ERA) in PAH pts at low-intermediate risk.#ambrisentan + #tadalafil vs pooled monotherapy resulted in a delayed time to clinical failure (HR 0.50 – 95% CI, 0.35-0.72; P<0.001).
— cardio-met (@cardiomet_CE) January 3, 2024
🔓 https://t.co/YqS197gu31
20c) The combination of AMB + TAD was well tolerated, although more patients presented peripheral edema compared with both monotherapies. AMBITION set the stage of a new era in the management of #PAH
— cardio-met (@cardiomet_CE) January 3, 2024
21b) Triple therapy was no better to decrease PVR, improve 6MWD, or decrease #NTproBNP
— cardio-met (@cardiomet_CE) January 3, 2024
🔓 https://t.co/4yRRjwFg8s pic.twitter.com/qTOzuJws6h
22a) So where do we stand with combo #PDE5i + an #ERA?
— cardio-met (@cardiomet_CE) January 3, 2024
a. initial combination therapy (low – intermediate risk status)
b. sequential combination therapy in patients not at goal
c. initial combination therapy with IV #prostanoids (high risk status)
d. all of the above
23) Large multicenter clinical trials with #riociguat are supporting the inclusion of the drug in the treatment algorithm of #PAH. In which specific setting?
— cardio-met (@cardiomet_CE) January 3, 2024
a. Sequential combination on oral ERA background
b. Replacement of PDE5i
c. Both a and b
d. Initial combination therapy
25a) In PATENT-1, 443 #PAH patients were randomized to receive placebo vs #riociguat in individually adjusted doses up to 2.5 mg TID, or riociguat capped at 1.5 mg TID (for exploratory purposes). Background PAH therapy was allowed, with oral #ERA or non parenteral #prostanoids
— cardio-met (@cardiomet_CE) January 3, 2024
26) The study population was predominantly female (79%), aged 51±17 y, mostly #iPAH (61%) or associated with #CTD (25%), in @WHO FC II (42%) or III (53%) on background therapy in 50% (44% ERA). Baseline #6MWD was 363±69 m
— cardio-met (@cardiomet_CE) January 3, 2024
28) What about dosing? At week 12, 75% of the patients were receiving #riociguat 2.5 mg TID and 15% 2.0 mg TID, or 90% at least 2 mg TID. A decrease in dose was observed in only 12% vs 9% in the placebo group
— cardio-met (@cardiomet_CE) January 3, 2024
30) Clinical worsening and adverse events are presented below. Patients on rio had more hypotension vs placebo, but more discontinuations due to AE were observed in the latter group (7% vs 3%). pic.twitter.com/DzWlaFsJsA
— cardio-met (@cardiomet_CE) January 3, 2024
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)https://t.co/00ps8yg6x7 pic.twitter.com/nVuNndQ4dW
— cardio-met (@cardiomet_CE) January 3, 2024
34) 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/YIukUMbs4j
— cardio-met (@cardiomet_CE) January 3, 2024
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)
— cardio-met (@cardiomet_CE) January 3, 2024
🔓 https://t.co/4rkNr7fYoe
🔓 https://t.co/MUnZPdQ0aS
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 pic.twitter.com/xDF7ez5r03
— cardio-met (@cardiomet_CE) January 3, 2024
38c) What about high-risk patients? Well, they should be on parenteral #prostacyclin, together with oral combination therapy with #ERA and #PDE5i pic.twitter.com/8uj7T45gfv
— cardio-met (@cardiomet_CE) January 3, 2024
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! pic.twitter.com/9uecBnzY07
— cardio-met (@cardiomet_CE) January 3, 2024
41b) The efficacy and safety of #MK_5475 in #PAH is being tested in the Ph 2/3 #INSIGNIA_PAH study. In an adaptive design, a total of 450 patients with persistent symptoms will be included in sequence.
— cardio-met (@cardiomet_CE) January 3, 2024
42) 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
— cardio-met (@cardiomet_CE) January 3, 2024
44) And WHEW!! That was like TEN #6MWT because you just earned a full HOUR of 🆓 CE/#CME! Claim your certificate now at https://t.co/UkyF9yFvwc and then FOLLOW US for more expert-authored #MedEd! Thanks to outstanding faculty @jeanlucvachiery for joining our @cardiomet_ce team!
— cardio-met (@cardiomet_CE) January 3, 2024