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In This Issue
- This Week in 30 Seconds
- The Lead: ACC.26 Preview
- Diltiazem + DOACs
- Orforglipron PDUFA
- Diabetic Cardiomyopathy Debate
- New on the Site
- The Week Ahead
- Myth-Buster of the Week
- The Foot Stomper
This Week in 30 Seconds
- ACC.26 opens Saturday in New Orleans — CHAMPION-AF (LAAO vs. DOACs), CORALreef AddOn (oral PCSK9 inhibitor enlicitide), and Heartline (Apple Watch AF detection) lead 27 late-breaking trials across 72 hours.
- Orforglipron PDUFA date is April 10 — the first non-peptide oral GLP-1 receptor agonist could receive FDA approval within days, removing the injection barrier for millions of patients with obesity and type 2 diabetes.
- Diltiazem + DOAC bleeding signal grows — a new Annals of Internal Medicine study quantifies the risk: 5.4 extra serious bleeding events per 1,000 person-years, rising sharply above 120 mg/day of diltiazem.
The Lead
ACC.26: The Trials That Could Change Your Monday Morning
The 76th ACC Annual Scientific Session opens March 28 in New Orleans with a late-breaking program that touches every major domain in cardiovascular medicine. Here are the presentations most likely to change practice:
CHAMPION-AF is the trial the entire atrial fibrillation community is watching. This randomized trial of the WATCHMAN FLX left atrial appendage closure device versus DOACs in 3,000 AF patients without contraindications to anticoagulation will either confirm or challenge the troubling CLOSURE-AF results from last week. If CHAMPION-AF also shows LAAO falling short of medical therapy, expect a fundamental rethinking of when device-based stroke prevention should be offered. If it diverges, the field will need to reconcile two contradictory datasets in real time.
CORALreef AddOn brings Merck’s oral PCSK9 inhibitor enlicitide to the ACC stage. The CORALreef Lipids trial already demonstrated a 57% LDL reduction at 24 weeks. AddOn data will show how enlicitide performs on top of existing statin therapy — a critical question for the millions of patients not reaching their new 2026 guideline LDL targets.
Heartline is the first large-scale randomized trial of consumer-device-driven AF screening. Using Apple Watch and iPhone to detect AF in older adults without a prior diagnosis, this study addresses the fundamental question of whether earlier detection through wearable technology translates into better outcomes — or just more diagnoses.
🏥 What This Means in Clinic
If you manage AF patients who have been offered or are considering LAAO, hold the referral conversation until CHAMPION-AF results are available. For lipid patients not at their 2026 guideline targets despite maximally tolerated statins, CORALreef AddOn data may open a new oral treatment pathway that avoids injections entirely.
🗣 What to Ask Your Doctor
“I heard there are major new heart study results coming out this weekend. Should any of them change my current treatment plan — especially around my cholesterol medication or my blood thinner?”
What’s Hot
💊 Diltiazem + DOACs: A Common Combination With Uncommon Risk
A study published in the Annals of Internal Medicine quantifies what pharmacologists have warned about for years: diltiazem, a moderate CYP3A4/P-glycoprotein inhibitor commonly used for heart rate control in AF, increases plasma concentrations of apixaban and rivaroxaban by 31% and 40%, respectively. The clinical result: 5.4 additional serious bleeding events per 1,000 person-years compared to metoprolol. At diltiazem doses above 120 mg daily, the difference jumps to 9.2 extra events per 1,000 person-years.
This matters because the combination is extraordinarily common. Diltiazem is a first-line rate control agent in AF, and DOACs are standard anticoagulation. Many patients are on both without any dose adjustment or heightened monitoring.
🏥 What This Means in Clinic
Review your AF patients currently on diltiazem plus apixaban or rivaroxaban. For those on diltiazem doses above 120 mg/day, consider switching to a beta-blocker for rate control or, if diltiazem is necessary, discussing the bleeding trade-off explicitly. This is not a reason to stop anticoagulation — it is a reason to optimize the rate control agent.
💊 Orforglipron: The Oral GLP-1 That Could Change Everything — PDUFA April 10
Orforglipron, Eli Lilly’s non-peptide oral GLP-1 receptor agonist, has a PDUFA date of April 10 under the FDA’s National Priority Voucher program. Unlike oral semaglutide, which requires strict fasting conditions, orforglipron can be taken without food restrictions — a meaningful quality-of-life improvement for patients.
Phase 3 ATTAIN-1 data showed the 36 mg dose achieved 11.2% body weight reduction at 72 weeks, with 54.6% of patients losing at least 10% of their body weight. If approved, orforglipron would be the first small-molecule oral GLP-1, potentially removing the injection barrier that has limited uptake for millions of patients with type 2 diabetes and obesity.
🗣 What to Ask Your Doctor
“I’ve been hesitant about GLP-1 medications because of the injections. I heard a pill version might be approved soon. Would I be a candidate for that instead?”
🧠 The “Diabetic Cardiomyopathy” Debate: Does It Actually Exist?
The Heart Failure Association of the ESC has published a clinical consensus statement concluding that evidence for “diabetic cardiomyopathy” as a distinct disease entity remains unconvincing. The argument: after accounting for hypertension, coronary artery disease, obesity, and other comorbidities, there may be no unique myocardial pathology attributable solely to diabetes.
This doesn’t change treatment — SGLT2 inhibitors, GLP-1 RAs, and RAAS blockade remain foundational. But it challenges how we communicate with patients. Telling someone they have “diabetic cardiomyopathy” implies a distinct disease with a distinct pathway — which may oversimplify a much more complex cardiometabolic picture.
New on the Site
Follow the Leader (Dyslipidemia Phenotype) UPDATED
Major refresh incorporating the 2026 ACC/AHA Guideline’s restored LDL targets, new ApoB goals, and the VESALIUS-CV implications for aggressive lowering across all ASCVD patients.
From the Daily Briefs This Week
JenaValve Trilogy FDA approval (first TAVR for aortic regurgitation — a historic structural heart milestone) • Visceral fat outperforming BMI for heart failure risk prediction (EPI|Lifestyle data) • Guideline-at-a-Glance implementation summary in JACC • Expert reactions to the 2026 Dyslipidemia Guideline including removal of mandatory ezetimibe-before-PCSK9i sequencing.
The Week Ahead
ACC.26 Scientific Sessions, New Orleans
Twenty-seven late-breaking presentations. Must-watch: CHAMPION-AF, Heartline, CORALreef AddOn, SCOUT-HCM (mavacamten in adolescent HCM), HI-PEITHO (intermediate-high risk PE), KARDINAL (antisense therapy for uncontrolled hypertension), and acoramidis long-term data in ATTR cardiomyopathy. Full coverage throughout the weekend.
Orforglipron PDUFA Date
FDA decision expected on the first small-molecule oral GLP-1 receptor agonist. If approved, anticipate rapid formulary discussions and prior authorization pathway development.
Lp(a)HORIZON Results Expected
The Phase 3 pelacarsen cardiovascular outcomes trial (NCT04023552) could be the first to demonstrate that lowering Lp(a) reduces cardiovascular events — a potential paradigm shift for the estimated 1 in 5 adults with elevated levels.
Myth-Buster of the Week
“Diltiazem Is Interchangeable With Beta-Blockers for Rate Control in AF”
The Myth
In clinical practice, diltiazem and beta-blockers like metoprolol are treated as largely interchangeable options for heart rate control in atrial fibrillation. The choice often comes down to physician habit, patient tolerance, or formulary availability — with little attention to drug interaction profiles when a DOAC is on board.
The Evidence
The Annals of Internal Medicine study demonstrates this assumption has consequences. Diltiazem inhibits the same metabolic pathways (CYP3A4 and P-glycoprotein) that clear apixaban and rivaroxaban from the body. The result is effectively an unintended dose increase of the anticoagulant — producing 5.4 extra serious bleeding events per 1,000 person-years. For patients on diltiazem above 120 mg/day, the bleeding excess nearly doubles.
The Bottom Line
Diltiazem remains an appropriate rate control option in selected patients, particularly those who cannot tolerate beta-blockers or who have concurrent conditions favoring calcium channel blockade. But when a DOAC is part of the regimen, the bleeding interaction deserves explicit consideration — not an afterthought. Review the rate control agent before escalating the anticoagulant.
🗣 What to Ask Your Doctor
“I take diltiazem for my heart rate and a blood thinner for my atrial fibrillation. I read that this combination might increase bleeding risk. Should we review whether a different heart rate medication would be safer for me?”
🦶 The Foot Stomper
The 2026 guideline restored LDL targets. VESALIUS-CV proved aggressive lowering works in primary prevention. CORALreef showed an oral PCSK9 inhibitor can cut LDL by 57%. And orforglipron may soon give us the first GLP-1 pill without injection barriers.
📌 ACC.26 starts Saturday. Pay attention.
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