The MI paradox of risk scores, the CELEBRATE trial of a new subcutaneous glycoprotein IIb/IIIA inhibitor (with its funny endpoint), the SURPASS CVOT trial, and the bad story of andexanet alfa are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I What do risk scores mean for individuals? Or perhaps a better question: Is a first MI preventable?

• Limitations of Screening in Predicting First MI https://www.jacc.org/doi/10.1016/j.jacadv.2025.102361
• Sudden Death Due to Cardiac Arrhythmias https://www.nejm.org/doi/abs/10.1056/NEJMra000650
• UMC Amsterdam group (EHJ) https://academic.oup.com/eurheartj/article/46/38/3762/8181058

II CELEBRATE Trial

• CELEBRATE Trial https://evidence.nejm.org/doi/full/10.1056/EVIDoa2500268

III SURPASS CVOT Trial Published

Aug 01, 2025 This Week in Cardiology Podcast

https://www.medscape.com/viewarticle/1002781

• SURPASS-CVOT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2505928
• REWIND Trial 10.1016/S0140-6736(19)31149-3 External Link

IV FDA Pulls Andexanet Alfa From the Market

• ANNEXA 4 https://www.nejm.org/doi/10.1056/NEJMoa1814051
• ANNEXA I https://www.nejm.org/doi/full/10.1056/NEJMoa2313040
• Richard Buka Tweet https://x.com/richardbuka/status/2001045834050216327?s=20

V Mandrola's Top Cardiovascular Stories of 2025

https://www.medscape.com/viewarticle/mandrolas-top-10-cardiovascular-stories-2025-2025a1000yuh

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An elegant study in post-TAVI atrioventricular block, a PSA for my structural colleagues, revascularization in women, and a CTO PCI trial are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I AV Block After TAVR

Heart Blocks During vs After TAVR Show Distinct Patterns

https://www.medscape.com/viewarticle/heart-blocks-during-vs-after-tavr-show-distinct-patterns-2025a1000ypp

• Mechanisms Underlying Alterations in Cardiac Conduction After TAVR https://jamanetwork.com/journals/jamacardiology/fullarticle/2842748

II Related PSA Announcement to My Structural Colleagues

III Revascularization Strategies in Women with Severe Chronic CAD

Women With Chronic Severe CAD Fare Better With CABG vs PCI

https://www.medscape.com/viewarticle/women-chronic-severe-cad-fare-better-cabg-vs-pci-2025a1000ygd

• PCI vs CABG in Women With Chronic CAD https://doi.org/10.1093/eurheartj/ehaf806
• PCI vs CABG - Meta-Analysis of 4 RCTs https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02334-5/abstract
• CABG vs Drug-Eluting Stent Implantation for CAD - Meta-Analysis https://www.jacc.org/doi/10.1016/j.jcin.2016.10.008
• RECHARGE trial https://therechargetrial.com/

IV A CTO PCI RCT – But don't get your hopes up

• Early vs Late-Staged PCI After Subintimal Tracking and Re-entry for CTO https://doi.org/10.1016/j.jacc.2025.09.1598
• DECISION CTO trial https://pubmed.ncbi.nlm.nih.gov/30813758/
• National Inpatient Sample Database PCI CTO Associated With Higher Mortality https://pubmed.ncbi.nlm.nih.gov/37356643/

V Mandrola's Top 10 Stories

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Less is more after PCI, the TARGET-FIRST trial, a negative blood pressure trial that is actually positive, aspirin vs OAC for bleeding, AEDs, and Factor XI is not dead yet are the topics discussed by John Mandrola, MD, on this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Less is More: TARGET-FIRST

• TARGET-FIRST Trial https://www.nejm.org/doi/10.1056/NEJMoa2508808
• STOPDAPT-2 ACS Trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2789701

II A Negative Trial That Is Actually Positive

• The RETREAT-FRAIL Study https://www.nejm.org/doi/full/10.1056/NEJMoa2508157

III Major Bleeding With Aspirin vs Apixaban

• Subanalysis of ARTESiA https://jamanetwork.com/journals/jamacardiology/fullarticle/2841075
• ARTESiA Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2310234
• AVERROES Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1007432

IV High Value Interventions – The AED

• Experts Call for AED Placement on All Commercial Aircraft https://www.medscape.com/viewarticle/experts-call-aed-placement-all-commercial-aircraft-2025a1000xzf

• In-Flight Sudden Cardiac Arrest and AED Use 10.1016/j.cjca.2025.10.010 External Link

V Factor XI Inhibitors – OCEANIC STROKE trial

• Bayer Press Release on Asundexian https://www.bayer.com/en/us/news-stories/oceanic-stroke

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Listener feedback, huge news in the world of carotid disease with the CREST-2 publication, prasugrel beats ticagrelor again, and a big coffee trial are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Listener Feedback

• Complete Revascularization for Acute MI Meta-analysis https://doi.org/10.1016/S0140-6736(25)02170-1

II A Sea Change in the Treatment of Carotid Artery Disease — CREST-2 Published

• ECST-2 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(25)00107-3/fulltext
• SPACE-2 https://pubmed.ncbi.nlm.nih.gov/36115360/
• CREST-2 Trial www.nejm.org/doi/full/10.1056/NEJMoa2508800
• CREST Protocol paper https://pmc.ncbi.nlm.nih.gov/articles/PMC5987521/

III Prasugrel Beats Ticagrelor in High-Risk Patients With Diabetes After PCI https://www.medscape.com/viewarticle/prasugrel-beats-ticagrelor-high-risk-patients-diabetes-after-2025a1000wbt

• PLATO trial https://www.nejm.org/doi/full/10.1056/NEJMoa0904327
• Ticagrelor or prasugrel vs clopidogrel in PCI https://eurointervention.pcronline.com/article/ticagrelor-or-prasugrel-versus-clopidogrel-in-patients-undergoing-percutaneous-coronary-intervention-for-chronic-coronary-syndromes
• ISAR-REACT 5 trial https://www.nejm.org/doi/full/10.1056/NEJMoa1908973

IV Another Coffee and AF study

Can Coffee Cut the Risk for Atrial Fibrillation?

https://www.medscape.com/viewarticle/can-coffee-cut-risk-atrial-fibrillation-2025a1000w11

A Coffee a Day to Keep the AFib Away? The DECAF Trial Discussed https://www.medscape.com/viewarticle/coffee-day-keep-afib-away-decaf-trial-discussed-2025a1000v5z

• DECAF trial https://jamanetwork.com/journals/jama/fullarticle/2841253

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Listener feedback on the PISCES trial, AHA news (including a big PCSK9i trial), beta-blockers post MI, LAAC, and post-AF ablation OAC use are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Listener Feedback

Why I Believe Fish Oil's Big CV Benefit in Dialysis Patients https://www.medscape.com/viewarticle/why-i-believe-fish-oils-big-cv-benefit-dialysis-patients-2025a1000uzg

• PISCES trial https://www.nejm.org/doi/full/10.1056/NEJMoa2513032

II PCSK9 Inhibitor News

In Global Trial, PCSK9 Inhibitor Provides Major Protection Against First CV Event https://www.medscape.com/viewarticle/global-trial-pcsk9-inhibitor-provides-major-protection-2025a1000uzp

• VESALIUS-CV trial https://www.nejm.org/doi/full/10.1056/NEJMoa2514428
• ODYSSEY trial https://www.nejm.org/doi/full/10.1056/NEJMoa1801174
• FOURIER https://www.nejm.org/doi/full/10.1056/NEJMoa1615664
• Anish Koka Tweet on LDL-lowering https://x.com/anish_koka/status/1987280506937909326?s=20

III Beta-Blockers After MI and John Cleland

• Beta-Blockers after MI with normal EF https://www.nejm.org/doi/full/10.1056/NEJMoa2512686
• REBOOT-CNIC trial https://www.nejm.org/doi/full/10.1056/NEJMoa2504735
• REDUCE AMI trial https://academic.oup.com/ehjcvp/article/9/2/192/6895544?login=false
• ABYSS trial https://www.nejm.org/doi/full/10.1056/NEJMoa2404204
• CAPITAL RCT trial https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199347
• Beta-Blockers after MI with mildly reduced EF https://pubmed.ncbi.nlm.nih.gov/40897190/
• John Cleland Clinical Outlook https://www.nature.com/articles/s41569-025-01228-w

IV Left Atrial Appendage Closure – The CLOSURE-AF trial

Percutaneous LAAC in AF Falls Short Again in CLOSURE-AF https://www.medscape.com/viewarticle/percutaneous-left-atrial-appendage-closure-af-falls-short-2025a1000uzu

• Prague-17 Trial https://www.jacc.org/doi/10.1016/j.jacc.2020.04.067
• OPTION trial https://www.nejm.org/doi/full/10.1056/NEJMoa2408308

V Oral AC after AF ablation – the OCEAN Trial

Anticoagulation After AF Ablation: The OCEAN Trial Still Leaves Questions https://www.medscape.com/viewarticle/anticoagulation-after-af-ablation-ocean-trial-still-leaves-2025a1000v4t

• OCEAN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2509688
• ALONE-AF trial https://jamanetwork.com/journals/jama/fullarticle/2838294

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Listener feedback on non-culprit PCI in STEMI, a major cardiac result in patients on hemodialysis, news on GLP-1 agonists, a dubious stroke trial, and an AHA preview are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Listener Feedback

• Meta-analysis of MI as a surrogate https://pubmed.ncbi.nlm.nih.gov/34694318/
• Compare Acute Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1701067
• DANAMI-3–PRIMULTI 10.1016/S0140-6736(15)60648-1 External Link
• CULPRIT-SHOCK https://www.nejm.org/doi/full/10.1056/NEJMoa1710261

II Huge Cardiac News for Patients with ESRD PISCES article EMBARGOED Till 1130 AM EST

• PISCES Trial www.nejm.org/doi/full/10.1056/NEJMoa2513032
• REDUCE-IT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1812792
• STRENGTH Trial https://jamanetwork.com/journals/jama/fullarticle/2773120
• FISH trial https://jamanetwork.com/journals/jama/fullarticle/1150094

III Obesity Agents

• White House announces deal with Lilly and Novo on GLP-1 drugs https://www.reuters.com/business/healthcare-pharmaceuticals/novo-lilly-shares-rise-trump-obesity-drug-deal-nears-2025-11-06/

Amylin Agonists

• Amylin Analog Eloralintide Reduces Weight in Phase 2 Trial

https://www.medscape.com/viewarticle/amylin-analog-eloralintide-reduces-weight-phase-2-trial-2025a1000uqf

• Eloralintide Phase 2 Study https://doi.org/10.1016/S0140-6736(25)02155-5

GLP-1 Comparisons

• SURMOUNT-5 Trial https://www.nejm.org/doi/10.1056/NEJMoa2416394
• Tirzepatide vs Semaglutide in 10-year CVD Risk Reduction https://doi.org/10.1093/ehjopen/oeaf117

IV A Problematic Trial in Stroke Care

• LAMP trial https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2840370

V AHA Preview

AHA 2025: Mandrola's Four Trials to Look For https://www.medscape.com/viewarticle/aha-2025-mandrolas-four-trials-look-2025a1000u80

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Four pillars of cardiology today, stable coronary artery disease, severe aortic stenosis, the evaluation of chest pain, and best therapies for atrial fibrillation are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Stable CAD Complete vs culprit-only revascularization at time of STEMI

• iMODERN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2512918
• PRAMI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1305520
• COMPLETE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1907775
• FULL REVASC Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2314149
• PCI Revascularization Strategies After MI https://www.jacc.org/doi/10.1016/j.jacc.2024.04.051
• CULPRIT SHOCK Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1710261
• How a Meta-Analysis Can Mislead https://www.sensible-med.com/p/how-a-meta-analysis-can-misleadthe

II SEVERE Aortic Senosis

7-Year PARTNER 3 Results – TAVI vs SAVR

• 7-year results PARTNER 3 https://www.nejm.org/doi/full/10.1056/NEJMoa2509766
• PARTNER 3 at 1 year https://www.nejm.org/doi/10.1056/NEJMoa1814052
• PARTNER 3 at 5 years https://www.nejm.org/doi/10.1056/NEJMoa2307447

III Functional vs Anatomic Assessment in Suspected CAD

• 10-year follow-up of PROMISE trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2838118
• PROMISE Trial https://www.nejm.org/doi/10.1056/NEJMoa1415516
• CCTA vs Functional Stress Test – Meta-Analysis https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2655243

IV ARREST AF

• ARREST AF trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2840225

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The PREVENT score in hypertension, GLP-1 mechanism of action in cardiovascular disease, CAD type and statin benefit, and the problem with hospitalization endpoints in HF trials are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Is the PREVENT Calculator Best for Determining CVD Risk? Insights From a Post Hoc Analysis of SPRINT Trial

https://www.medscape.com/viewarticle/prevent-calculator-best-determining-cvd-risk-insights-post-2025a1000svo

• PREVENT Calculator https://doi.org/10.1016/j.jacc.2025.07.037
• SPRINT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1511939

II GLP-1 Mechanism of Action in CV Disease

• Analysis of SELECT Trial 10.1016/S0140-6736(25)01375-3 External Link
• SELECT trial https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

III Statins and CAD Phenotype on CTA and Outcomes

• Interactions Between Statin Use, CAD Phenotypes on CTA https://www.jacc.org/doi/10.1016/j.jcmg.2025.05.018
• Statin Use for Primary Prevention of CVD https://jamanetwork.com/journals/jama/fullarticle/2795522

IV HHF Endpoints in Heart Failure Trials

• The Problem with Hospitalization Endpoints in HF Trials https://onlinelibrary.wiley.com/doi/10.1002/ejhf.70070

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Another knock against the antiplatelet/anticoagulant combo, polypills in HF, the physical exam of the future, and the problem of underpowered trials that even Bayesian analyses cannot rescue are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Listener Feedback

• Trends Study https://www.heartrhythmjournal.com/article/S1547-5271(11)00496-6/fulltext

II Another knock against the Antiplatelet/Anticoagulation combination

"Antiplatelet Plus Oral Anticoagulant Lowers Stroke, Raises Bleeding Risk" https://www.medscape.com/viewarticle/antiplatelet-plus-oral-anticoagulant-lowers-stroke-raises-2025a1000re0

• ATIS-NVAF Trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2839511
• AQUATIC trial https://www.nejm.org/doi/abs/10.1056/NEJMoa2507532

III Polypill for HFrEF

• A Multilevel Polypill for Patients With HFrEF https://www.jacc.org/doi/10.1016/j.jacadv.2025.102195

IV The Physical Exam of the Future

• Point-of-Care Ultrasound https://doi.org/10.1016/j.jchf.2025.102707

V More on Underpowered Trials – GA vs Moderate Sedation in IV stroke

• SEGA Trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2839838
• Bayesian Analyses of CV Trials https://doi.org/10.1016/j.cjca.2021.03.014

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GLP-1 use in HFrEF, left atrial posterior wall isolation during AF ablation, peri-device leaks for LAAO, new findings in post-cardiac surgery AF, and imaging before AF ablation are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I. Listener Feedback

HYPERION trial https://www.nejm.org/doi/10.1056/NEJMoa2508170

ZENITH trial https://www.nejm.org/doi/full/10.1056/NEJMoa2415160

II GLP1 Use in HFrEF

Effects of GLP-1s in Patients With HFrEF https://doi.org/10.1016/j.jchf.2025.102573

FIGHT Study https://jamanetwork.com/journals/jama/fullarticle/2540402

FIGHT Study Post-hoc Analysis https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14862

Substudy of EXSCEL Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.041659

III LA Posterior Wall Isolation Saga

Failure of PW Wall Isolation by PFA with Epicardial Mapping https://doi.org/10.1016/j.jacep.2025.08.017

IV Peridevice Leaks After LAAO

IMPRESSION LAAC Study https://doi.org/10.1016/j.jacep.2025.08.014

V Post Cardiac Surgery AF

Monitoring of New-Onset AF After CABG https://jamanetwork.com/journals/jama/fullarticle/2839710

PACES trial https://clinicaltrials.gov/study/NCT04045665

VI TEE vs ICE Before AF ablation

ICE vs TEE Study https://jamanetwork.com/journals/jamacardiology/fullarticle/2839370

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