Ruey Hu: Hello, everyone, and welcome back to my channel. Today we're going to talk about the 2025 American College of Cardiology and American Heart Association guideline for the management of patients with acute coronary syndromes which were released on February 27.th Ruey Hu: What do you need to know? The document is packed with valuable information spanning 72 pages, excluding references. So I want to break it down for you and highlight the most important changes. Ruey Hu: My focus on this talk is not to go through every single statement in every area. Instead, I'm going to do a side by side comparison of the new and old guidelines. So we can focus on what changed because most viewers of this channel are already familiar with the existing standard of care. Ruey Hu: The 2025 acs. Guideline updates recommendations from 5 previous guidelines, the 2013 guideline on stemi, the 2014 guideline on nstemi, the 2015 focused update on Pci in stemi, the 2016 focused update on dapt in CAD and the 2021 revascularization guidelines. Ruey Hu: An audio version of this lecture is also available on spotify and apple podcasts. Ruey Hu: I'm going to do a deep dive on 4 key pillars that were updated. Revascularization, strategy, dual antiplatelet therapy, lipid management and mechanical circulatory support. Ruey Hu: Let's start with revascularization strategy. Ruey Hu: Previously the 2021 guideline for revascularization said in selected hemodynamically stable patients with stemi and multivessel disease after successful primary pci stage Pci, of a significant non-infarct artery stenosis is recommended to reduce the risk of death, or mi. That was a class one recommendation, the 2025 guideline is pretty much the same thing Ruey Hu: in selected hemodynamically stable patients with stemi and multivessel disease, after successful pci of the infarct related artery, pci of significantly stenosed non-infarct related arteries is recommended to reduce the risk of death or mi and improve angina related quality of life. Ruey Hu: Why? Ruey Hu: Because recent studies suggest a lower risk of mace predominantly driven by a lower rate of recurrent ischemia and recurrent mi. When multivessel stenting occurs, the guideline made this recommendation on the basis of the results of the Prami trial and the complete trial. Ruey Hu: the Prami trial which stands for preventive, angioplasty and acute myocardial infarction, randomized patients with stemi and multivessel disease to complete revascularization versus culprit, artery, only revascularization. Ruey Hu: The trial was stopped early, due to a significant reduction in the primary composite endpoint, cardiovascular death non-fatal mi or refractory angina, with complete revascularization, with significant reductions in non-fatal mi and refractory angina, and had a trend in reduction in the rates of cardiovascular death Ruey Hu: the complete trial which stands for complete versus culprit. Only your vascularization strategies Ruey Hu: to treat multivessel disease after early pci or stemi randomized patients with stemi and significant multivessel disease to stage Pci. Of the non-infrag-related artery performed up to 45 days post-mi or culprit vessel, only revascularization with Pci reserved for patients with refractory symptoms here's a visual abstract from cardiomerds Ruey Hu: at a medium follow-up of 3 years. Multivessel Pci reduced cardiovascular death, or mi and cardiovascular death mi or ischemia-driven revascularization this benefit was consistent across all subgroups. Of course, the benefits of complete revascularization with multivessel Pci should not be extrapolated to patients with disease more suited to cabbage surgery because they were excluded from these trials Ruey Hu: previously, the 2015 focus. Update on Pci for Stemi, said Pci, of a non-infarcted artery may be considered in selected patients with stemi and multivessel disease, who are hemodynamically stable, either at a time of primary pci or as a planned stage procedure. Class 2 B Ruey Hu: for the non infarc lesions. The 2025 guideline no longer considers stage revascularization to be the same as revascularization. At the time of primary Pci. The latter is given a gentle bump up, although the overall recommendation remains weak as a 2 b recommendation. Ruey Hu: Specifically, the 2025 guideline says, in selected hemodynamically stable patients with stemi and low complexity, multivessel disease, those not intended for cabbage, surgery, multivessel pci of significantly stenosed, non-infrac-related arteries at the time of primary Pci may be prepared over a stage approach to reduce the risk of cardiovascular events. 2. B. Ruey Hu: What's the rationale for this? Ruey Hu: They say, performing multivessel Pci, at a time of primary Pci offers the convenience of a single procedure, allowing for faster recovery, without the risk of repeated arterial access, or the potential for recurrent ischemia before the stage. Pci. Ruey Hu: The guideline made this recommendation on the basis of the results of the Biovast trial and the multistars ami trial. So let's take a look at those Ruey Hu: the biovasc trial which stands for direct, complete versus stage complete revascularization in patients presenting with acute coronary syndromes and multivessel disease, randomized patients with acs, including 40%, with stemi and multivessel disease to a strategy of single setting immediate multivessel, pci, or stage multivessel pci. Here's an abstract from acc visual abstract from Acc. Ruey Hu: At one year immediate multivessel Pci was not inferior to stage multivessel pci for the primary endpoint of all-cause death, mi unplanned ischemia-driven revascularization or cerebrovascular events when compared with stage Pci. A single procedure, Multivessel Pci was associated with lower rates of recurrent mi and lower rates of unplanned ischemia-driven revascularization Ruey Hu: the multistars ami trial which stands for multivessel immediate versus stage revascularization and acute myocardial infarction compared a strategy of single procedure. Multivessel Pci with stage multivessel Pci in patients with stemi and multivessel disease. Here's the visual abstract from esc Ruey Hu: immediate multivessel Pci was non-inferior and superior to stage multivessel Pci for the primary endpoint of death reinfarction stroke unplanned ischemia-driven revascularization or hospitalization for heart failure. At one year this was largely driven by a lower rate of recurrent ischemia and recurrent infarction in the immediate group Ruey Hu: in a network meta-analysis. Comparing all strategies for managing the non-infrat-related artery. A single procedure approach for immediate multivessel Pci was preferred followed by stage multivessel Pci. Ruey Hu: What do they mean by patients who are ideally suited for immediate, complete revascularization? Ruey Hu: They're referring to patients with uncomplicated pci of the infarct related artery and low complexity, non-infarct related artery disease with stable hemodynamics, normal Lv filling pressures and normal renal function. So there are a bunch of caveats to that. Ruey Hu: Now the above statements were for Stemi. What about nstemi? Ruey Hu: Previously the wisdom to revascularize non-infarct lesions was only for Stemi, and was much weaker in nstemi. Now they have upgraded the recommendation to encourage revascularizing non-infarct lesions. In nstemi. The 2014 nstemi guidelines had previously said. Ruey Hu: a strategy of multivessel pci in contrast to culprit lesion only Pci may be reasonable in patients undergoing coronary vascularization as part of treatment for Nst. Elevation Acs. Class 2 B. At the time. Ruey Hu: The 2025. Guideline now says, in stable patients with Nst. Elevation. Ruey Hu: acs with multivessel disease, but without left main stenosis, who are not intended for cabbage, surgery, and undergoing culprit lesion, pci, pci, of significant non-culprit lesions at the time of index procedure, or as a stage procedure, is recommended to reduce the risk of mace. That's a class one recommendation. Ruey Hu: So note that not only have they upgraded the recommendation to encourage revascularizing non-infarct lesions in nstemi, they have updated the class recommendation from 2 B to one. Ruey Hu: Also pay attention to the fact that the 2025 guideline says that in n-stemi you can revascularize the non-culprit lesions, either at the time of the index procedure, or as a stage procedure, but for stemi revascularization of the non-infarct lesions at the time of index Pci is preferred over a stage approach to reduce the risk of cardiovascular events. As long as you meet the caveats that I mentioned in the Prior Slide. Ruey Hu: when it comes to Pci of non-infarct lesions. In patients who present with cardiogenic shock the guidance remains the same as before. Ruey Hu: The 2021 guideline for revascularization, said in patients with Stemi, complicated by cardiogenic shock, routine pci of a non-infarcted artery at the time of primary pci should not be performed because of the higher risk of death or renal failure. That's class 3 harm Ruey Hu: the 2025. Guideline still says the same thing in patients with Stemi, complicated by cardiogenic shock, routine pci of non-infarct related. Artery at the time of primary Pci should not be performed because of the higher risk of death or renal failure. Class 3. Harm. The guideline made this recommendation on the basis of the results of the culprit shock trial. So let's take a look at that. Ruey Hu: The culprit shock trial which stands for culprit lesion only pci versus multivessel, pci and cardiogenic shock. Randomized patients with acute myocardial infarction, approximately 60% with stemi and cardiogenic shock to a strategy of complete multivessel, pci, or culprit vessel only. Pci. Here's a visual abstract from Acc Ruey Hu: at 30 days and one year the rates of death or need for renal replacement therapy were significantly higher in the group of patients randomized to multivessel Pci. Ruey Hu: That being said, it should also be noted that the culprit shock trial only permitted enrollment. If there was an identifiable culprit lesion in situations where an unstable appearing non-culprit artery lesion was observed, or in those patients with an uncertain culprit lesion. The decision to proceed with multivessel pci may be more nuanced Ruey Hu: for nstemi, the 2021 revascularization guidelines said in patients with nst elevation acs who present in cardiogenic shock. Routine multivessel pci, of non-culprit lesions in the same setting should not be performed. Class 3. Harm. Ruey Hu: the 2025. Guideline still says the same thing in patients with Nst. Elevation acs complicated by cardiogenic shock. Routine Pci of a non-culprit artery at the time of index procedure, should not be performed because of the higher risk of death or kidney failure class 3. Harm Ruey Hu: that covers the updates regarding revascularization strategy. Now we will move on to the second update area, dapt Ruey Hu: the 2016, focus guideline update on dwell antiplatelet therapy said in patients with Acs that's stemi or non-st elevation acs treated with dapt after Bms. Or des Stent. Implantation, p. 2, y. 12. Inhibitor therapy with clopidogrel, prazogrel, or Ticagalor, should be given for at least 12 months. That's a class one recommendation. Ruey Hu: the 2025 guideline made minimal changes to this one Ruey Hu: in patients with Acs who are not at high bleeding, risk death with aspirin and an oral. P. 2 y. 12. Inhibitor should be administered for at least one year to reduce mace class one recommendation. So they just added that last part about reducing mace. Ruey Hu: Regarding the choice of dapt agent. The 2016 focus update on dapt said in patients with Acs, that's nst elevation acs or Stemi treated with dapt after coronary stent implantation. It is reasonable to use Ticagalor in preference to clopidogrel for maintenance of p. 2 y. 12. Inhibitor therapy that's a class 2, a recommendation. Ruey Hu: The 2025. Guideline has bumped this preference up from class 2 a. To class one in 2 statements in patients with Nst. Elevation undergoing Pci. Prasagrel, or Ticlor, is recommended to reduce mace and stent thrombosis. Class one, and in patients with Stemi managed with primary Pci prasagrel or ticlor should be administered to reduce mace and stent thrombosis class one. Ruey Hu: Regarding early de-escalation from Dapt to Sapt, the 2021 revascularization guidelines said in selected patients undergoing Pci. Shorter duration, dapt of one to 3 months, is reasonable. With subsequent transition to p. 2, i. 12. Inhibitor monotherapy, to reduce the risk of bleeding events. Class 2. A. Ruey Hu: The 2025. Guideline refines the transition period from one to 3 months to one month, specifically suggestlor as a monotherapy agent instead of clopidogrel or prasigol, and bumps this up from Class 2. A to class one. Ruey Hu: they say, in patients with acs who have tolerated daft with ticagalor transition to ticagular monotherapy at one month. Post. Pci is useful to reduce bleeding risk class. One recommendation Ruey Hu: results from several randomized trials, including twilight acs. Ultimate dapt Tpas and Tico have consistently shown that in patients who underwent pci for acs after one to 3 months of ticagular-based dapt aspirin withdrawal, followed by ticagular monotherapy, results, in less bleeding without clear excess. Mace, as compared with continued dapt. Ruey Hu: Although studies examining this strategy were previously critiqued for having relatively low rates of ischemic events, meta-analyses conducted at the study level and individual patient level, pooled across studies have yielded similar results. Ruey Hu: The guideline specifically recommends Ticagalor as a monotherapy agent based on our results for clopidogrel as monotherapy that have been mixed. The stop Dapt 2 acs. Trial showed that de-escalating from dapt to clopidogrel monotherapy at one to 2 months is associated with increased risk of mace compared to continued dapt. Ruey Hu: Some have posited that this excess thrombotic risk might be due to patient heterogeneity in inadequate platelet inhibition to Clopidogrel observed in 30 to 40% of patients after Pci. Ruey Hu: Although the on-treatment, pharmacodynamic effects of Ticaglore and Prasagrel are similar. The safety of Prasagrel monotherapy has not been established in patients after one month post acs. So the guideline does not explicitly mention prazogrel as a monotherapy option. And here's a visual abstract from esc on the stop dap. 2 acs. Trial that compared one month dual antiplate therapy, followed by clopidogrel, monotherapy, and acs Ruey Hu: regarding patients who undergo pci for Acs, but who have high bleeding risk. The 2016 focus guideline update on Dapt said in patients with Acs treated with dapt after des implantation, who develop a high risk of bleeding. Ruey Hu: such as treatment with oral anticoagulant therapy. Ruey Hu: are at high risk of severe bleeding complications, such as major intracranial surgery or develop significant overt bleeding. This continuation of p. 2, i. 12. Inhibitor therapy after 6 months may be reasonable. That's a class 2 B recommendation. Ruey Hu: The 2025 guideline allows a single antiplatelet agent to either be aspirin or a p. 2 y. 12. Inhibitor, and has brought forward the transition time from dap to single antiplatelet therapy from 6 months to one month Ruey Hu: in patients with acs undergoing pci, who are at high bleeding risk transition to single antiplatelet therapy. That's aspirin or p. 2 y. 12. Inhibitor after one month may be reasonable to reduce bleeding risk. That's a class 2 B. Recommendation Ruey Hu: in the master dapt trial which stands for management of high bleeding risk patients. Post bioresorbable Polymer coated stent implantation with an abbreviated versus standard dapt regimen Ruey Hu: patients at high risk of bleeding who had completed a four-week course of dapt after successful pci with drug-eluting stents, were randomly allocated to single antiplatelet therapy, or more prolonged dap, defined as at least 2 additional months. Compared with standard therapy. An abbreviated antiplatelet strategy demonstrated non-inferiority with respect to composite ischemic events and superiority regarding clinically relevant bleeding over one year Ruey Hu: of note. In the absence of oral anticoagulant use, the choice of discontinuing aspirin, or p. 2. A. 12. Inhibitor, and the choice of p. 2. A. 12. Inhibitor was at the discretion of the treating physician. Ruey Hu: Although the trial demonstrated non-inferiority for abbreviated daft with respect to mace in patients with high bleeding risk. Ruey Hu: it was underpowered to determine the relative safety of discontinuing aspirin. Versus p. 2, i. 12. Inhibitor. Ruey Hu: and I have to acknowledge the Esc Congress for giving this visual abstract here. Ruey Hu: Note that there are 2 statements here, because one is going from dual antiplatelet therapy to single antiplatelet therapy, and the other is going from a stronger. P. 2, i. 12. Inhibitor to a less strong. P. 2, i. 12. Inhibitor. Specifically the 2025. Guideline says in patients with Acs undergoing Pci, the escalation of dapt switching from Ticaglo or Prasagrel to Clopidogrel after one month may be reasonable to reduce bleeding risk. That's a class 2 B recommendation Ruey Hu: now, the de-escalation from higher to lower intensity. P. 2, y. 12. Inhibitor in general can be guided by the results of platelet function assays that quantify the degree of platelet inhibition among patients treated with clopidogrel or be unguided in the guided method. Patients with adequate response may continue to receive clopidogrel, whereas non-responders are switched to a more potent. P. 2 y. 12. Inhibitor Ruey Hu: clopidogrel responsiveness may also be inferred with the use of genotyping assays that identify polymorphisms in genes involved in clopidogrel metabolism. Ruey Hu: clinical trials, examining guided de-escalation of p. 2, y. 12. Inhibitor therapy. Intensity after pci have either shown a lack of benefit, as in the antarctic trial non-inferiority as in the tropical Acs, trial or reductions in minor bleeding, as in a popular genetics trial. Because of the mixed nature of these results, guided de-escalation of p. 2, y. 12. Inhibitor. Intensity is not explicitly recommended in the 2025. Guideline. Ruey Hu: In contrast, unguided de-escalation refers to p. 2. I. 12. Inhibitor intensity, de-escalation that is performed without antecedent knowledge of platelet responsiveness. Ruey Hu: the topic and tailless ami trials suggested that unguided de-escalation of p 2 i. 12 inhibitor intensity one month after Pci reduces bleeding without incurring ischemic risk compared with longer-term, prasigrel, or Techagolor-based dapt. Meanwhile Triton Timi and Pegasus Timi trials suggested that the benefit of more potent. P. 2, i. 12. Inhibitor therapy extends beyond the early phase post Acs, but with increased bleeding. Ruey Hu: Because of the mixed nature of these results, unguided de-escalation of p. 2, i. 12. Inhibitor intensity has a weak 2 B recommendation. In the 2025 guidelines. Ruey Hu: Patients with acs frequently also have indications for anticoagulant therapy, such as Doaccowarfarin, including afib venous thromboembolism and prosthetic heart valves Ruey Hu: regarding the duration of triple therapy in patients who are already on an antithrombotic agent. The 2014 nstemi guidelines said, the duration of triple antithrombotic therapy with a vitamin K. Antagonist aspirin, and a p. 2 i 12. Receptor inhibitor in patients with Nst. Elevation acs should be minimized to the extent possible to limit the risk of bleeding. That was Class one. Ruey Hu: the 2025 guideline now explicitly suggests a transition time, and also suggests which p. 2, i. 12. Inhibitor to use, they say, in patients with Acs who require oral anticoagulant therapy aspirin should be discontinued after one to 4 weeks of triple antithrombotic therapy, with continued use of p. 2. I. 12. Inhibitor therapy, preferably clopidogrel and oral anticoagulant to reduce the bleeding risk class. One recommendation. Ruey Hu: Several randomized trials have demonstrated that the discontinuation of aspirin, one to 4 weeks after Pci reduces the risk of bleeding in patients with Afib, with an indication for dapt and an oral anticoagulant, including redwhile, Pci, pioneer, Afib, Pci, and Augustus. Ruey Hu: Although individual studies were not powered for ischemic endpoints. Meta-analyses across randomized trials suggest no difference in mortality stroke and overall mace when aspirin is discontinued for patients on an oral anticoagulant albeit with a marginal apparent increase in mi and synthrombosis. Ruey Hu: reflecting the part that some trials gave triple therapy for one week, while others gave triple therapy. For 4 weeks the guideline does not explicitly dictate whether to go with one week or 4 weeks. It says that in patients with a high risk of stent throbrosis, triple therapy with aspirin, for up to 30 days after Pci could be considered. Ruey Hu: p. 2, i. 12. Inhibitor therapy should be continued for at least 12 months after Pci. Following aspirin discontinuation, but could be discontinued earlier in those with multiple risk factors for bleeding. Ruey Hu: regarding which, p. 2 i. 12. Inhibitor agent to use alongside the antithrombotic agent. Trials of more potent. P. 2. I. 12. Inhibitors, such as Prasagrel and Ticragilor, excluded patients requiring long-term anticoagulation. Therefore clopidogrel is generally favored as the p. 2, i. 12. Inhibitor. In this setting for most patients. Ruey Hu: I will close off this section by giving you the Flowchart Ruey Hu: for most patients for all patients with Acs. The default strategy is at least 12 months of dapt in the leftmost column with Ticlo or Prasaglo bring preferred post. Pci. That's a class one recommendation in green Ruey Hu: for patients with high bleeding risk. Post Pci. For Acs. In the rightmost column. Either the aspirin or p. 2, i. 12. Inhibitor, can be stopped at one month, transitioning to single antiplatelet therapy, using either the remaining aspirin or p. 2, i. 12. Inhibitor class 2 B Ruey Hu: in the second column for Acs patients post-pci in general, it is okay to transition from dap to sap single antiplatelet therapy. But the monotherapy agent during the period of sap should be Ticagalor. Specifically, that's a class one recommendation Ruey Hu: in a 4th column, doing a Ruey Hu: unguided de-escalation of p. 2, i. 12. Inhibitor therapy from aspirin plus ticagula or prasagrel to aspirin plus clopidogrel is also something that can be considered. That's a class 2 B recommendation Ruey Hu: in the middle column for Acs. Patients who have a need to be on an antithrombotic triple therapy with an antithrombotic. P. 2, i. 12. Inhibitor and aspirin can be transitioned to single antiplatelet plus antithrombotic anywhere between one to 4 weeks. Post Pci. This is Class One Ruey Hu: and credit to American Heart Association for contributing this slide Ruey Hu: that covers the updates regarding dapt. The next area is about lipid management. Ruey Hu: This time I will start by giving you the Flowchart. Then I will go through the individual statement updates, and why they made them Ruey Hu: credit to the Acc slide deck for this particular slide Ruey Hu: for every patient hospitalized with Acs. If the patient is not on a statin yet, or if they are only on a low intensity or moderate intensity. Statin then initiate a high intensity. Statin. That's a class one recommendation and consider concurrent edition of Ezetimibe. That's a class 2. B recommendation. Ruey Hu: If the patient's already on a maximally tolerated statin regimen, if the Ldl is still more than 70 inclusive, add a non-statin therapy that's a class one recommendation. If the Ldl is 55 to 69, consider adding a non-statin. Ldl lowering therapy, that's a class 2, a recommendation. Ruey Hu: If the Ldl. Is less than 55. Then there's nothing to add. Just continue the statin class. One recommendation. Ruey Hu: if the patient is statin intolerant, or declines to take a statin, add a non-statin Ldl lowering therapy. That's the class. One recommendation Ruey Hu: for all of the above. You should reassess the lipid profile in 4 to 8 weeks after discharge and adjust therapy as needed to achieve lipid targets. Class one recommendation. Ruey Hu: the 2025 acs. Guideline makes 4 statements about lipids that had no corresponding statement in earlier guidelines. Ruey Hu: The 1st statement about lipids is just a minor rewording Ruey Hu: from the prior 2014 N. Stemi guideline, and 2013 stemi guideline. High intensity. Statin therapy should be initiated or continued in all patients with Stemi 2013. Class one, or N. Stemiacs, 2014. Class one, and no contraindications to its use. The 2025 guidelines. Minor rewarding update is in patients with acs. High intensity. Statin therapy is recommended to reduce the risk of Mace class one recommendation. Ruey Hu: So it is added that mace part Ruey Hu: here is the 1st of the 4 guideline recommendations, with no prior equivalent in patients with Acs, who are already on maximally tolerated statin therapy with Ldl of 70, and above adding a non-satin lipid lowering agent is recommended to further reduce the risk of Mace class. One recommendation. Ruey Hu: non-statin lipoloring agents include Ezetamime, Evalocamab, Aliracumab incluserin, and bepidoric acid. Most of these medications were not routinely available at the time of the 2013 stemi and 2014 nstemi guidelines. Ruey Hu: The 2025 guideline notes that incluseran lowers Ldl-c levels by 50%. But clinical outcome studies were still pending at a time of guideline writing. Ruey Hu: second in patients with acs who are statin intolerant non-statin, lipid lowering therapy is recommended to lower Ldl and reduce the risk of mace. That's a class. One recommendation to consider a patient as having statin intolerance. A minimum of 2 statins should be attempted, including at least one at the lowest approved daily dose. So the definition of that still has not changed. Ruey Hu: 3rd in patients with Acs. The concurrent initiation of Azitamib in combination with maximally tolerated statin may be considered to reduce the risk of mace. That's a class 2 B recommendation. Ruey Hu: This 2 B recommendation is supported by the results that improve it. Trial which studied the combination of Simvastatin and Azitami, 40 milligrams and 10 milligrams respectively versus simvastatin, and placebo. That's simvastatin monotherapy in patients hospitalized with an Acs. In the past 10 days. The addition of azitamime reduced the relative risk of mace by 6.4% compared with placebo. That's a hazard ratio of 0 point 9 3 6 over a median of 6 years follow-up. Ruey Hu: 4, th in patients with Acs who are already on maximally tolerated statin therapy with Ldl. Cholesterol, 55 to 69, Ruey Hu: adding a non-statin. Lipid lowering therapy is reasonable to reuse the risk of mace. That's a class 2. A recommendation Ruey Hu: prior to this guideline, no guideline explicitly addressed a population of patients who were already at an Ldl. Level of 55 to 69 at the time of Acs. Ruey Hu: This 2. A recommendation is supported by the fact that in improveit, which randomized patients post Acs with Ldl levels between 50 and 125 to Simvastatin and Azitami versus Simvastatin placebo. The benefit of Azitamib addition in post Acs, period was similar among patients with Ldl. Of 50 to 70 versus 70, and up Ruey Hu: the Pcsk. 9. Inhibitor trials Foray and Odyssey outcomes enrolled patients with Ldl. Cholesterol of 70 and above, and thus did not specifically assess outcomes associated with adding Pcsk. 9. Inhibitor therapy among patients with Ldl levels of 55 to 70. Ruey Hu: However, secondary analyses of both Fourier and Odyssey showed better outcomes in patients with achieved Ldl levels under 50 versus those with achieved Ldl levels above 50 inclusive with monotonic relationships suggesting better outcomes with progressively lower Ldl cholesterol even well below 50, Ruey Hu: and that covers the updates regarding lipid management. Ruey Hu: The 4th key area and the last one is regarding mechanical circulatory support. Ruey Hu: The 2025 guideline includes a new recommendation about using the impella or microaxial flow. Pump device in cardiogenic shock. Ruey Hu: Cardiogenic shock is a core part of the acs. Guidelines. As cardiogenic shock occurs in 10% of patients with Stemi and has an early mortality rate of 40% to 50%. Ruey Hu: Impela was previously not mentioned in the 2013 Stemi guideline, or the 2014 nstemi guideline Ruey Hu: impella, was mentioned indirectly in a 2021 revascularization guideline, but for a different indication that is for complex Pci. Specifically the 2021 revascularization, Guideline had said, and sorry I didn't paste it in here, but it said in selected high-risk patients. Elective insertion of an appropriate hemodynamic support device as an adjunct to pci may be reasonable to prevent hemodynamic compromise during pci Ruey Hu: the 2025 guideline explicitly mentions impella in selected patients with stemi, and severe or refractory cardiogenic shock. Insertion of a microaxial intravascular flow pump is reasonable to reduce death Ruey Hu: the guideline made this recommendation on the basis of the results of the danger shock trial, which we will look at right after this Ruey Hu: and this slide I obtained from the Acc slide deck for their guidelines. Ruey Hu: Previously, small studies of Impella did not demonstrate clinical benefit for patients with acute mi and cardiogenic shock, including Isar shock which stands for efficacy. Study of Lv. Assist. Device to treat patients with cardiogenic shock. Ruey Hu: The impress and severe shock trial which stood for impella versus iabp reduces mortality. In Stemi patients treated with primary pci in severe cardiogenic shock and impelastic, which was impella program. The Sutien O techniques in avant e co twose Ruey Hu: the dangerous shock trial which was the Danish German cardiogenic shock trial at 14 centers across Europe enrolled patients with stemi and cardiogenic shock of less than 24 h duration and randomized them to use a microaxial flow. Pump or standard of care, use of a microaxial flow pump significantly reduced the risk of all-cause mortality at 180 days by 26%, which corresponded to a hazard ratio of 0 point 7 4, and a number needed to treat of 8, Ruey Hu: and here is a visual abstract of danger shock from American College of cardiology. Ruey Hu: However, although there was a mortality benefit, the class of recommendation is limited at 2 B. Due to the increased risk of serious complications like bleeding limb, ischemia and renal replacement therapy with impelas seen in the danger, shock, trial. Ruey Hu: use of an impella is reasonable to reduce mortality in patients with stemi and cardiogenic shock, who have clinical features consistent with the inclusion criteria of the danger shock trial. Ruey Hu: What are the gist of these criteria? Cardiogenic shock was defined as hypotension, systolic blood pressure? Less than 100 or vasopressor support and organ hyperperfusion that's an arterial lactate of 2.5 or higher, and or Svo 2 less than 55% with normal Pao 2 and Lv ejection fraction less than 45% Ruey Hu: patients who are comatose. That's a Glasgow scale score of less than 8 after out of hospital cardiac arrest and patients with overt right ventricular failure were excluded. Ruey Hu: Patients with Stemi, who present with sky shock stages, CD. Or E, who are non-comatose and have adequate peripheral vasculature to accommodate large bore access are reasonable candidates for microaxial flow. Pump. Ruey Hu: Note that the timing of Impella placement was not specified by the trial protocol, so the preferred timing of impella placement is unclear Ruey Hu: overall. More data are needed to guide selection of patients for Mcs. The timing of Mcs placement and duration of support and strategies to reduce the risk of vascular complications, bleeding and limb. Ischemia. Ruey Hu: apart from the new statement about Impella, the 2025 guideline also includes a statement recommending against the routine use of balloon pump and va ecmo in acute mi and cardiogenic shock. Ruey Hu: Specifically, it says in patients with ami and cardiogenic shock, the routine use of intraaortic balloon pump or Va ecmo is not recommended due to a lack of survival. Benefit class 3. Ruey Hu: No benefit. Ruey Hu: Previously Ruey Hu: the 2013 stemi Guideline had said, the use of iabp is reasonable in patients with cardiogenic shock after Stemi, who do not quickly stabilize with pharmacologic therapy. Class 2. A Ruey Hu: previously the 2015 Aha! Scientific statement on mechanical circulatory support, had said, Va ecmo can be considered in patients through refractory cardiogenic shock. However, there is a paucity of randomized clinical trial data to support its routine use. There's no class of recommendation with that statement, since that was a scientific statement. Instead of a guideline. Ruey Hu: the 2025 guideline made the class 3. Recommendation about balloon pump on the basis of the results of the Iabp shock. 2. Trial. This is a figure I took from the main paper of the Iabp shock, 2 trial which stands for intraaortic balloon pump and cardiogenic shock. 2. Ruey Hu: That trial randomized patients with acute mi and severe or refractory cardiogenic shock, in whom early revascularization was planned to intraaortic balloon pump or no iabp Ruey Hu: at 30 days, and at 6 years follow-up no differences were observed between the Iabp and no Iabp arm in the primary outcome of all-cause death. Nor were there differences in recurring myocardial infarction stroke repeat revascularization, rehospitalization for cardiac reasons or quality of life. Ruey Hu: The guideline made the classy recommendation about Va. Ecmo on the basis of the results of the Ecmo. Cs. And ecls shock trials. Ruey Hu: Here's a visual abstract from Cardio nerds, the Ecmo Cs trial. Ruey Hu: which stands for extracorporeal membrane oxygenation in the therapy of cardiogenic shock randomized patients with rapidly deteriorating or severe cardiogenic shock to immediate or no immediate Va ecmo. At 30 days no differences were observed in the primary composite endpoint of all-cause death resuscitated cardiac arrest and implementation of another Mcs device. Ruey Hu: Here's a visual abstract of the Acls shock trial from visual med Ruey Hu: the trial which stands for extracorporeal life support and infarct-related cardiogenic shock randomized patients with acute myocardial infarction and severe or refractory cardiogenic shock, in whom early vascularization was planned to early ecls or no ecls. Ruey Hu: no differences were observed between the Ecls versus no ecls arm in the primary outcome of the 30 day mortality rate, or secondary outcomes, moderate or severe bleeding and peripheral vascular complications requiring intervention were higher in the Ecls versus no Ecls arm Ruey Hu: overall va ecmo has not been shown to reduce death compared with medical therapy alone in patients with cardiogenic shock in the setting of Mi, but increases major bleeding and vascular complications. Ruey Hu: So if balloon pump and Va Ecmo are no longer recommended for routine use in acute mi with cardiogenic shock, as of 2025. What other situations are we still allowed to use it in. Ruey Hu: So I searched all of the Haacc sky and Hfsa guidelines that are still valid and not replaced by a subsequent guideline, and I found 3 scenarios where use is still supported by the guideline scenario, one Ruey Hu: per the 2021. Revascularization guideline in selected high-risk patients, elective insertion of an appropriate hemodynamic support devices in adjunctive Pci may be reasonable to prevent hemodynamic compromise during Pci. That's a class 2 B recommendation. Ruey Hu: That being said, this statement mainly applies to Impella as the 2021 guideline notes, intraaortic balloon pump. Contrapulsation provides minimal hemodynamic support for Pci, but improves coronary and cerebral perfusion Ruey Hu: scenario. 2. Per the 2022 heart failure, guideline in patients with advanced hfref and hemodynamic compromise and shock. Temporary Mcs, including percutaneous and extracorporeal ventricular assist devices are reasonable as a bridge to recovery or bridge to decision. Class 2. A Ruey Hu: scenario, 3 per the 2025 acs. Guideline in patients with mechanical complication of Acs. Short-term Mcs. Devices are reasonable for hemodynamic stabilization as a bridge to surgery. That's a class 2. A recommendation. Ruey Hu: Now, how about Va ecmo? I searched the same guideline sets from Aha, Acc. Sky and Hfsa, and found 2 scenarios that are still supported by the guidelines. Scenario one per the 2020. Resuscitation guideline. There's insufficient evidence to recommend the routine use of extracorporeal Cpr. For patients with cardiac arrest. Ruey Hu: But Ecpr. May be considered for select cardiac arrest patients for whom the suspected cause of the cardiac arrest is potentially reversible during a limited period of mechanical cardiorespiratory support. That's a class 2. B recommendation Ruey Hu: scenario, 2 for the 2022 heart failure, guideline in patients with advanced hfref and hemodynamic compromise and shock. Temporary Mcs, including percutaneous and extracorporeal ventricular assist devices are reasonable as a bridge to recovery, a bridge to decision. That's a class 2, a recommendation Ruey Hu: that covers the updates regarding mechanical circulatory support. Ruey Hu: I will end by giving you the top take-home messages from the guideline writers themselves. Ruey Hu: Their 1st take-home message is the following, dual antiplatelet therapy is recommended for patients with acute coronary syndromes, ticagolor or prasigrel is recommended in preference to clopidogrel in patients with Acs who are undergoing Pci in patients with Nst. Elevation acs who are scheduled for an invasive strategy with timing and Angiography to be more than 24 h upstream. Treatment with Clopidogrel or Ticagolor may be considered to reduce mace. Ruey Hu: next, which we also talked about dapt with aspirin and an oral. P. 2 y. 12. Inhibitor is indicated for at least 12 months as the default strategy in patients with Acs who are not at high bleeding risk. Ruey Hu: Several strategies are available to reduce bleeding risk in patients with Acs who have undergone pci and required antiplatelet therapy. Ruey Hu: A in patients at risk of gastrointestinal bleeding. A proton pump inhibitor is recommended. Ruey Hu: B. In patients who have tolerated daft with ticagalor transition to tricagular monotherapy is recommended after one month of Pci. After Pci or C. In patients who require long-term anticoagulation. Aspirin discontinuation is recommended, one to 4 weeks after Pci. With continued use of a p. 2 y. 12 inhibitor. Ruey Hu: preferably clopidogrel, 3, rd one. Ruey Hu: High intensity. Statin therapy is recommended for all patients with acs, and with the option to initiate concurrent azitami a non-statin, lipid lowering agent, such as azitamime, evalacam, aliracumab, and glycerin, or bempidoric acid, is recommended for patients already on maximally tolerated statin who have a low density Ldl. Of 70 or above. Ruey Hu: It is reasonable in this high risk population to further intensify lipid lowering therapy. If the Ldl level is 55 to 70, and already on maximally tolerated Ruey Hu: Statin. Ruey Hu: Next in patients with Nst. Elevation Acs. Who are at high or intermediate risk of ischemic events, an invasive approach with intent to proceed with revascularization is recommended during hospitalization, to reduce mace in patients with Nst. Elevation acs who are at low risk of ischemic events, routine, invasive or selective, invasive approach with further risk. Stratification is recommended to help identify those who may require revascularization and to reduce major adverse cardiovascular events. Ruey Hu: Note that for some of these take home messages. They're covering topics which I did not explicitly address and compare to the old guidelines. But these are not, you know, controversial. Take home messages, which is why I did not spend time kind of dissecting them. Ruey Hu: Next, 2 procedural strategies are recommended in patients with Acs, who are undergoing Pci. A. A radial approach is preferred over thermal approach in patients with acs undergoing pci to reduce bleeding, vascular complications, and death and intravascular imaging is recommended to guide Pci in patients with Acs with complex coronary lesions. So also not controversial. Ruey Hu: We've known that for a while. Ruey Hu: Next, a strategy of complete revascularization is recommended in patients with St. Elevation Mi. Or Nst. Elevation acs. The choice of revascularization method, that is, cabg versus multivessel Pci. In Nsc elevation acs and multivessel disease should be based on the complexity of the coronary, artery, disease, and comorbid conditions. Ruey Hu: Pci, of significant non-culprit stenosis for patients with St. Elevation, Mi can be performed in a single procedure or stage, with some preference towards performing multivessel Pci in a single procedure Ruey Hu: in patients with Acs and cardiogenic shock. Emergency revascularization of the culprit vessel is indicated, however, routine pci of the non-infart-related arteries at the time of pci is not recommended. Ruey Hu: Next, based on one trial use of the microaxial flow pump in selected patients with cardiogenic shock related to acute mi is reasonable to reduce death. Ruey Hu: however, complications such as bleeding limb, ischemia, and renal failure, are higher with a microaxial flow pump reduced compared with usual care. Therefore, careful attention to vascular access and weaning of support is important to appropriately balance the benefits and risks Ruey Hu: next, red blood cell transfusion to maintain a hemoglobin of 10 milligrams. Sorry 10 grams per deciliter may be reasonable in patients with acs and acute or chronic anemia who are not actively bleeding. Ruey Hu: Finally, after discharge Ruey Hu: focus on secondary prevention is fundamental, a fasting lipid panel is recommended 4 to 8 weeks after initiating or adjusting the dose of lipid lowering therapy Ruey Hu: referral to cardiac rehabilitation is also recommended with the option for home-based programs for patients unable or unwilling to attend in person. Ruey Hu: I think that's very important. Ruey Hu: Thank you very much for listening. That is the summary and comparison of the 2025 American College of Cardiology and American Heart Association, guideline for the management of patients with acute coronary syndromes