The five most important cardiology papers of the week, summarised and analysed for cardiologists, trainees and cardiovascular clinicians. See what's advancing the field, why it matters, and what to do with it. Every Monday.
Launch offer: first month free. Cancel any time.
The Rhythm is an editorially independent digest with no commercial relationships with pharmaceutical or device companies.
How it works
Every week we scan hundreds of publications: NEJM, JACC, Circulation, Lancet and more. We then hand-pick the five papers that matter most for clinical practice.
Our Cardiology Intelligence Briefing does the reading for you. Each paper is summarised, contextualised and assessed for clinical relevance so you stay current without spending hours in journals.
In your inbox before your week begins. Read it over coffee. Stay ahead of your colleagues. Never miss a landmark trial again.
Sample issue: Week of 10 November 2025 · AHA Scientific Sessions, New Orleans
AHA 2025 will not be remembered for a single disruptive trial. It will be remembered for a collective shift in how cardiology thinks about evidence and restraint. Three themes define this week: Prevention is being pushed upstream into populations who have never had a heart attack or stroke.1 Device therapy is being held to the same evidential standard as drug therapy, and in at least one high-profile case it has failed that test.2 Long-established prescribing habits are being dismantled by evidence that finally separates the patients who benefit from those who do not.3 The message from New Orleans is that smarter treatment, not more treatment, is the direction of travel. This week gives you the evidence to practise accordingly.
If you read one thing this week
This week's five papers
What they studied
12,257 patients with established atherosclerosis or high-risk diabetes but no prior MI or stroke were randomised to evolocumab 140mg every two weeks or placebo, added to standard lipid-lowering therapy, over a median follow-up of 4.6 years.
What they found
Evolocumab reduced the 3-point major adverse cardiac events (MACE) composite by 25% versus placebo (6.2% vs 8.0%; hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.65-0.86). First MI was reduced by 36%. Adverse event rates were similar between the two groups with no safety concerns identified. Median LDL was reduced to 45 mg/dL in the evolocumab arm versus 109 mg/dL with placebo.
Why it matters clinically
This is the first major randomised trial to show PCSK9 inhibitor benefit specifically in patients with no prior MI or stroke, providing Level 1 evidence for a population previously without it. VESALIUS-CV fills an important evidence gap, providing a clear randomised evidence base for patients with atherosclerosis or high-risk diabetes who remain above LDL targets on maximally tolerated statins. The trial was funded by Amgen, manufacturer of evolocumab, though the double-blind design mitigates the most significant concerns around industry sponsorship.
In context
FOURIER established PCSK9 inhibition in secondary prevention. VESALIUS-CV extends that benefit upstream, before the first event occurs, making the case for treatment across the full continuum of high-risk patients.
Should this change your practice?
Yes. For patients with established atherosclerosis or high-risk diabetes who remain above LDL targets despite maximally tolerated statin therapy, evolocumab now has a clear randomised evidence base. Guideline updates from the European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) are anticipated. The cost-effectiveness question remains relevant in the UK context but the clinical evidence is now compelling.
Read the paper →Study type: Phase 3 randomised double-blind placebo-controlled trial
References cited in this section
FOURIER: Sabatine MS et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. NEJM 2017;376:1713. https://www.nejm.org/doi/full/10.1056/NEJMoa1615664
What they studied
912 patients with atrial fibrillation (AF) at high risk of both stroke (mean CHA2DS2-VASc 5.2) and bleeding (mean HAS-BLED 3.0) were randomised to LAA closure or physician-directed best medical care including direct oral anticoagulants (DOACs) where appropriate, at centres in Germany. Mean age was 78 years. Median follow-up was 3 years.
What they found
LAA closure failed to meet non-inferiority for the composite primary endpoint of stroke, systemic embolism, cardiovascular or unexplained death, or major bleeding. Event rates were 16.8 per 100 patient-years with the device versus 13.3 per 100 patient-years with medical therapy (difference in restricted mean survival time -0.36 years; 95% CI -0.70 to -0.01; P=0.44 for non-inferiority). The increase was driven largely by embolic events and procedural complications.
Why it matters clinically
This is a strongly negative trial in the exact population where LAA closure is currently most widely used. In older patients at very high combined stroke and bleeding risk, the device not only failed to demonstrate benefit but was associated with significantly worse outcomes than optimised medical management. This challenges the fundamental premise that a procedural, one-time intervention is safer than lifelong anticoagulation in the highest-risk patients.
In context
This sets a critical contextual boundary ahead of the CHAMPION-AF results expected at ACC.26 in 2026. The two trials enrolled fundamentally different populations: CLOSURE-AF patients were older, with far higher bleeding and stroke risk, and the device arms included older-generation devices. Together they may help define who, if anyone, benefits from LAA closure.
Should this change your practice?
For clinicians considering LAA closure referral in older patients with very high combined stroke and bleeding risk (mean CHA2DS2-VASc 5.2, HAS-BLED 3.0), this trial should give considerable pause. LAA closure is not supported by current evidence in this population, and the data raise the possibility of net harm. Optimised medical therapy including DOACs where appropriate remains the better-evidenced strategy. Referral should be approached with considerable caution pending further data.
Read the paper →Study type: Prospective randomised controlled trial
What they studied
A patient-level meta-analysis of five randomised trials (REBOOT, REDUCE-AMI, BETAMI, DANBLOCK and CAPITAL-RCT; n=17,801) examined whether long-term beta-blocker therapy reduces outcomes in patients with a preserved left ventricular ejection fraction (LVEF) of 50% or above after MI, with no other indication for beta-blockade. Median follow-up was 3.6 years.
What they found
Beta-blocker therapy did not reduce the composite of all-cause death, MI, or heart failure in patients with preserved LVEF of 50% or above (8.1% vs 8.3%; HR 0.97; 95% CI 0.87-1.07; P=0.54). This was consistent across all five trials and across subgroups. Notably, the same research group separately reported in The Lancet at ESC 2025 that beta-blockers do confer benefit in patients with mildly reduced LVEF of 40-49% (HR 0.75; 95% CI 0.58-0.97).
Why it matters clinically
Beta-blocker prescription after MI has been near-universal for 40 years, based on pre-reperfusion era evidence. This is the largest and most definitive analysis to date showing no benefit in the largest subgroup of contemporary post-MI patients, those with preserved ejection fraction. The majority of patients successfully treated with PCI have preserved LVEF, meaning most patients currently on beta-blockers after MI may derive no benefit from continuing them.
In context
Taken together with the ESC 2025 Lancet meta-analysis, the picture is now substantially clearer: benefit appears to exist in mildly reduced LVEF (40-49%) and the most rigorous randomised data show no benefit in preserved LVEF (50% or above). The post-MI beta-blocker debate has been meaningfully advanced by this evidence, though formal guideline updates are still anticipated.
Should this change your practice?
Yes. For patients with preserved LVEF (50% or above) after MI with no other indication for beta-blockers, long-term therapy is not supported by the most recent randomised evidence. De-prescribing should be considered on a case by case basis, particularly in patients experiencing side effects or where no other indication exists. For patients with LVEF 40-49%, the Lancet meta-analysis supports continued use. Guideline revisions are anticipated from both the American College of Cardiology/American Heart Association (ACC/AHA) and ESC on the basis of these combined data.
Read the paper →Study type: Individual patient-level meta-analysis of five randomised controlled trials
References cited in this section
ESC 2025 Lancet meta-analysis: Rossello X et al. Beta-blockers after myocardial infarction with mildly reduced ejection fraction. Lancet 2025;406:1128. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01592-2/abstract
What they studied
Two parallel double-blind randomised trials (CORE-TIMI 72a and 72b; combined n=1,061) of olezarsen, an RNA-targeted therapy inhibiting apolipoprotein C-III, in patients with severe hypertriglyceridaemia (above 500 mg/dL) randomised to olezarsen 50mg, 80mg, or placebo for 12 months.
What they found
Placebo-adjusted triglyceride reductions of 50-72% were seen across both trials and both doses (P less than 0.001 for all comparisons). Crucially, acute pancreatitis events were reduced by 85% in the olezarsen arms. Reductions in apolipoprotein C-III, remnant cholesterol, and non-HDL cholesterol were also significant.
Why it matters clinically
Severe hypertriglyceridaemia affects a small but high-risk population where pancreatitis is the primary clinical threat. Current therapies achieve modest reductions and none have previously demonstrated a reduction in acute pancreatitis in a randomised trial. Olezarsen represents a genuinely new category of therapy for this population.
In context
This follows the ANGPTL3 and apoC-III inhibitor class of RNA-targeted therapies redefining treatment of genetic lipid disorders. Olezarsen targets the same apoC-III pathway as volanesorsen but with a significantly better tolerability profile.
Should this change your practice?
Not yet for most cardiologists. This is a subspecialty indication. For patients with confirmed severe hypertriglyceridaemia and recurrent pancreatitis despite current therapy, olezarsen represents a meaningful new option. Watch for regulatory submissions. Refer to a specialist lipid clinic.
Read the paper →Study type: Two parallel Phase 3 randomised double-blind placebo-controlled trials
What they studied
CELEBRATE randomised 2,467 patients with STEMI presenting within 4 hours of symptom onset to subcutaneous zalunfiban (either 0.11 or 0.13 mg/kg, pooled for analysis) or placebo, administered at first medical contact by emergency services before primary PCI. The hierarchical composite primary endpoint at 30 days included all-cause death, stroke, recurrent MI, acute stent thrombosis, new or recurrent heart failure, large infarct size, or no major event.
What they found
The primary composite endpoint significantly favoured zalunfiban (adjusted OR 0.79; 95% CI 0.65-0.98; P=0.028). Severe or life-threatening bleeding (GUSTO criteria) was not significantly different between groups (1.2% vs 0.8%; P=0.4). However, mild to moderate bleeding was significantly increased with zalunfiban (6.4% vs 2.5%), as was access site bleeding. 13.3% of patients in the zalunfiban group had no major adverse endpoint at 30 days compared with 9.8% in the placebo group, an absolute difference of 3.5 percentage points.
Why it matters clinically
This is a conceptual revival of pre-hospital pharmacology, largely abandoned after the bleeding problems of earlier intravenous glycoprotein (GP) IIb/IIIa inhibitors. Zalunfiban's short half-life and subcutaneous delivery make it genuinely feasible for paramedic administration before the patient reaches the cath lab, potentially improving microvascular reperfusion at the time of primary PCI.
In context
Earlier agents in this class showed modest benefit but significant bleeding. Zalunfiban's pharmacology is specifically designed to overcome those limitations. This is the proof-of-concept trial and a larger confirmatory study is needed before this enters practice.
Should this change your practice?
Not yet. The absolute benefit is modest and the composite includes soft endpoints. This is a watch-this-space result that identifies a promising direction. If a larger confirmatory trial replicates these findings with a mortality benefit, pre-hospital GP IIb/IIIa inhibition may re-enter guidelines for the first time in over a decade.
Read the paper →Study type: Phase 3 international randomised double-blind placebo-controlled trial
What will change practice in the next 12 months
Coming up
The American Heart Association Scientific Sessions continue through 10 November with further major trial results still to come. Next week, we will cover any additional findings from the final sessions. Looking further ahead, the American College of Cardiology Scientific Session takes place in late March 2026 in New Orleans, where major trial data are anticipated including the CHAMPION-AF results on LAA closure versus NOACs, which will be one of the most consequential readouts in atrial fibrillation for several years.
The Rhythm is an independent cardiology research digest. Summaries are for informational purposes only and do not constitute medical advice. Always exercise your own clinical judgement. · © 2026 The Rhythm · rhythmcardio.co
Pricing
Launch offer: first month free on the monthly plan.
per month, cancel anytime
per year, saving £45
Launch offer: first month free. Annual plan from less than £2 a week.