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Oct 5Mon
  1. nature.com54

    Oral small-molecule GLP-1RA safiglipron versus dapagliflozin in type 2 diabetes: a randomized, double-blind, active-comparator-controlled phase 3 trial

    Once-daily oral safiglipron, a small-molecule GLP-1RA, was non-inferior to dapagliflozin for HbA1c reduction at all tested doses and superior at 90 mg in adults with type 2 diabetes in a randomized, double-blind, active-comparator-controlled phase 3 trial. Safiglipron gave greater improvements in glycemic control, similar modest weight loss, and an acceptable safety profile. It offers an oral alternative in the GLP-1 receptor agonist class.

    Why it matters: Phase 3 data show an oral GLP-1RA matching and at 90 mg beating dapagliflozin on HbA1c.

Oct 2Fri
  1. Nat Med61

    Effects of semaglutide on kidney disease in type 2 diabetes: a randomized placebo-controlled trial.

    Semaglutide's kidney protection in type 2 diabetes and chronic kidney disease may work through reduced vascular resistance and prevention of fibrosis. In a 52-week randomized trial of 106 participants, semaglutide 1 mg weekly lowered renal artery resistive index and stabilized the apparent diffusion coefficient versus placebo, while MRI coprimary outcomes (R2* oxygenation, perfusion, T1 inflammation) were unchanged. Paired biopsies showed pronounced effects on glomerular endothelial cells with fewer nearby immune cells.

  2. N Engl J Med69

    Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes.

    Once-weekly survodutide, a glucagon receptor-GLP-1 receptor dual agonist, produced mean weight reductions of 8.2% at 3.6 mg and 9.8% at 6.0 mg over 76 weeks in 752 adults with type 2 diabetes and BMI of 27 or more, versus 3.9% with placebo. At least 5% weight loss occurred in 57.6% and 64.5% of the survodutide groups versus 35.1% on placebo, with glycated hemoglobin falling 0.9 and 0.8 percentage points. Gastrointestinal adverse events, mostly mild to moderate, occurred in 72.8% and 77.7% of survodutide recipients.

    Why it matters: Phase 3 data show the dual agonist survodutide beats placebo for weight loss in adults with obesity and type 2 diabetes.

  3. Lancet71

    Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.

    Orforglipron, an oral non-peptide GLP-1 receptor agonist, was non-inferior to insulin glargine for four-component major adverse cardiovascular events in 2749 adults with type 2 diabetes at increased cardiovascular risk: MACE-4 occurred in 57 (4·2%) of 1358 orforglipron participants versus 67 (5·0%) of 1343 insulin glargine participants (HR 0·84; 95% CI 0·59-1·20) over a median follow-up of 2 years. Clinically significant or severe hypoglycaemia was less frequent with orforglipron (93, 6·8%) than insulin glargine (260, 19·2%), while gastrointestinal adverse events were more frequent (62·1% vs 14·2%). The results establish cardiovascular safety for a non-peptide GLP-1 receptor agonist, a class not previously studied for this outcome.

    Why it matters: First cardiovascular safety data for an oral non-peptide GLP-1 receptor agonist, a class not previously studied for cardiovascular outcomes.

  4. nature.com61

    Effects of semaglutide on kidney disease in type 2 diabetes: a randomized placebo-controlled trial

    A randomized placebo-controlled trial in individuals with type 2 diabetes probed the kidney-protective mechanisms of semaglutide using kidney histology, multiparametric MRI and transcriptomics. The findings indicate how semaglutide acts on the kidney in this population, moving the evidence beyond its established glucose-lowering effect toward direct renal mechanisms.

    Why it matters: Mechanistic trial data on semaglutide's kidney protection in type 2 diabetes using histology, MRI and transcriptomics.

Oct 1Thu
  1. JAMA59

    Permissive Blood Pressure Targets in Pediatric Critical Care: The PRESSURE Randomized Clinical Trial.

    A permissive mean arterial pressure target in hypotensive, invasively ventilated children did not change a composite of 30-day mortality and ventilation duration versus usual care (probabilistic index, 0.52; P = .23), while cutting median norepinephrine-equivalent total dose by 37.5%. The trial randomized 1900 patients across 23 PICUs in 3 countries. Kidney replacement therapy, adverse events and most secondary outcomes were similar, though surviving children left the PICU sooner (median 159 vs 166 hours). Clinicians can accept lower MAP targets and reduce vasoactive exposure without worsening outcomes.

    Why it matters: Large multicenter trial showing lower blood pressure targets in PICUs reduce vasoactive drug dose without harming 30-day outcomes.

  2. N Engl J Med82

    Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.

    Once-weekly retatrutide produced mean body-weight reductions of 17.6%, 23.7%, and 25.0% at 4, 9, and 12 mg over 80 weeks in 2339 adults with obesity without diabetes, versus 3.9% with placebo. In subgroups, WOMAC pain fell 3.5 and 3.6 points at 9 and 12 mg versus 1.9 with placebo in 574 participants with knee osteoarthritis, and apnea-hypopnea events per hour fell 34.3 and 31.7 versus 9.9 in 243 participants with obstructive sleep apnea. The phase 3 results extend triple-receptor agonist efficacy beyond weight to obesity-related pain and sleep outcomes.

    Why it matters: Phase 3 data show retatrutide's weight loss and benefits in knee osteoarthritis pain and obstructive sleep apnea.

  3. Lancet73

    Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.

    Once-weekly retatrutide produced dose-dependent weight loss in adults with obesity and type 2 diabetes over 80 weeks: mean bodyweight change was -16·8% with 9 mg and -18·8% with 12 mg versus -5·1% with placebo. In the phase 3 TRIUMPH-2 trial of 1152 participants, gastrointestinal adverse events were the most frequent, and discontinuation due to adverse events or death was higher with 9 mg and 12 mg than with placebo. The findings support retatrutide as a treatment option for obesity in people with type 2 diabetes.

    Why it matters: Phase 3 data show triple-agonist retatrutide achieves up to -18·8% bodyweight change in obesity with type 2 diabetes.

Sep 29Tue
  1. nature.com54

    Oral small-molecule GLP-1 receptor agonist safiglipron in early type 2 diabetes: a randomized, double-blind, placebo-controlled trial

    Once-daily oral small-molecule GLP-1 receptor agonist safiglipron reduced HbA1c by up to 1.45% versus placebo over 32 weeks in people with early type 2 diabetes not taking glucose-lowering medication, in the randomized OUTSTAND-1 trial. Body weight effects were modest. It offers an oral option with glycemic efficacy in this population.

    Why it matters: Oral small-molecule GLP-1 receptor agonists would replace injectable dosing for type 2 diabetes.

Sep 22Tue
  1. JAMA47

    Oxygen vs Air at Birth for Moderate- to Late-Preterm Infants: The AIROPLANE Cluster Randomized Crossover Trial.

    Starting resuscitation of 32-to-35-week neonates with Fio2 0.30 instead of 0.21 did not change the primary outcome: ongoing respiratory support when leaving the delivery room occurred in 72.6% vs 73.3% (risk difference, -0.83). In the cluster randomized crossover trial across 26 Australian maternity hospitals, 1818 newborns were enrolled, and Fio2 0.30 was associated with less escalation of delivery room support and less endotracheal ventilation beyond the delivery room (6.4% vs 9.3%).

    Why it matters: It answers an open question about initial oxygen for moderate- to late-preterm resuscitation with a large randomized comparison.

Sep 11Fri
  1. JAMA45

    Digital Outreach to Improve Statin Refills in Patients With Low Statin Adherence: The ADHERE-ASCVD Randomized Clinical Trial.

    Adaptive, sequential digital outreach modestly improved short-term statin refills among 20,604 adults with established ASCVD or high ASCVD risk and recent statin nonadherence. Initial outreach raised 14-day refill to 14.4% vs 12.0% with usual communication (adjusted risk ratio, 1.20), and second-stage outreach among nonresponders added further gains (13.0% vs 10.4%); switching modalities offered no benefit over repeating the same one. Cumulative 28-day refill was 24.9% vs 21.2%.

Sep 9Wed
  1. nature.com45

    Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial

    Mitiperstat, a myeloperoxidase inhibitor targeting the neutrophil–MPO inflammatory pathway, did not improve symptoms or exercise function in patients with heart failure with preserved or mildly reduced ejection fraction in a phase 2 randomized clinical trial. The finding argues against this anti-inflammatory approach as a symptomatic therapy in this population.

    Why it matters: Phase 2 trial of a neutrophil–MPO pathway inhibitor in HFpEF shows no benefit, informing drug development direction.

Sep 8Tue
  1. N Engl J Med63

    Tozorakimab to Prevent COPD Exacerbations.

    Add-on tozorakimab, an interleukin-33 inhibitor, cut the annualized rate of moderate or severe COPD exacerbations by roughly 30% in two replicate phase 3 trials, OBERON and TITANIA, with no eosinophil-count eligibility criteria. Among former smokers, rates fell from 1.90 to 1.34 events per year (rate ratio 0.71) in OBERON and from 2.07 to 1.37 (rate ratio 0.66) in TITANIA. It offers a biologic option for exacerbation prevention independent of eosinophil status.

    Why it matters: Phase 3 data show an IL-33 biologic reduces COPD exacerbations regardless of eosinophil count.

Sep 7Mon
  1. N Engl J Med50

    Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

    Balanced crystalloid fluid did not improve outcomes over 0.9% saline in children with septic shock. In the PRoMPT BOLUS trial, conducted at 47 emergency departments in five countries, a major adverse kidney event occurred in 3.4% of the balanced-fluid group (137 of 4235 patients) versus 3.0% of the saline group (124 of 4247 patients) (risk ratio, 1.10; 95% CI, 0.88 to 1.40). Hyperchloremia was more frequent with saline, 49.0% versus 31.4%, without affecting the primary outcome.

    Why it matters: Large multinational trial finds no kidney-outcome benefit of balanced fluid over saline in pediatric septic shock.

Sep 3Thu
  1. N Engl J Med47

    Targeted Use of Computed Tomographic Coronary Angiography in Acute Chest Pain.

    Routine outpatient CT coronary angiography did not reduce cardiac events in emergency department patients with suspected acute coronary syndrome after myocardial infarction had been ruled out and high-sensitivity troponin indicated intermediate risk. In the TARGET-CTCA trial of 3170 patients across 14 UK hospitals, the composite of myocardial infarction or death from cardiac cause occurred in 7.1% with CT angiography-guided care versus 7.3% with standard care over a median 3.0 years (adjusted hazard ratio 0.95, P = 0.71). The finding indicates further CT investigation of these intermediate-risk patients does not improve outcomes.

  2. N Engl J Med72

    Survodutide Once Weekly for the Treatment of Adults with Obesity.

    Once-weekly survodutide, a glucagon receptor-GLP-1 receptor dual agonist, produced mean body-weight reductions of 12.2% at 3.6 mg and 13.0% at 6.0 mg at week 76, versus 5.4% with placebo, in 725 adults with obesity but no diabetes. Weight loss of at least 5% occurred in 72.6% and 71.9% of the survodutide groups versus 46.3% on placebo (P<0.001). Gastrointestinal symptoms were the most common adverse events, and no deaths were reported.

    Why it matters: Phase 3 data show a dual glucagon-GLP-1 agonist outperforming placebo for weight loss in adults with obesity without diabetes.

Sep 2Wed
  1. Nat Med59

    Intramyocardial injection of allogeneic human induced pluripotent stem cell-derived cardiomyocytes in advanced ischemic heart failure: an early-stage randomized trial.

    Allogeneic human induced pluripotent stem cell-derived cardiomyocytes injected into the myocardium during CABG met the safety primary endpoint in the HEAL-CHF trial (n = 20): no sustained ventricular tachycardia in the 1- to 6-month window and no tumorigenicity at 12 months. All 10 cell-treated patients developed accelerated idioventricular rhythm within 4 weeks, and 2 had ventricular tachycardia over 140 bpm that resolved after cardioversion. Cell therapy improved 6-min walk distance, myocardial perfusion and relative wall thickening beyond CABG alone, but not ejection fraction, ventricular volumes, scar size, NYHA class or quality-of-life scores.

    Why it matters: First randomized evidence on safety and early efficacy of allogeneic hiPSC-derived cardiomyocyte injection in ischemic heart failure.

Sep 1Tue
  1. BMJ48

    Intravenous iron to treat anaemia before cardiac surgery (ITACS): international, double blind, placebo controlled randomised trial.

    Preoperative intravenous iron 1000 mg given 1-26 weeks before elective cardiac surgery to 955 adults with anaemia increased days alive and at home up to 90 days after surgery by a median of 1.0 day (95.4% CI 0.0 to 2.1, P=0.041) versus placebo. Red cell transfusion during hospital stay fell from 68.2% to 61.1% (relative risk 0.90, 95% CI 0.82 to 0.99, P=0.027). Major complications and length of stay did not differ.

  2. JAMA66

    Dapagliflozin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

    Dapagliflozin started one day before elective cardiac surgery cut postoperative acute kidney injury nearly in half. Among 784 adults randomized at Dutch hospitals, AKI within 7 days occurred in 28% of the dapagliflozin group versus 52% on placebo (relative risk, 0.54; P < .001). Four perioperative doses of 10 mg offer a preventive strategy where none had been identified.

    Why it matters: It identifies the first medication shown in a randomized trial to prevent AKI after elective cardiac surgery.

Aug 31Mon
  1. N Engl J Med64

    Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism.

    Catheter-directed thrombolysis with alteplase plus anticoagulation reduced the composite of death, recurrent pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days in intermediate-high-risk acute pulmonary embolism: 0.7% vs 6.8% with anticoagulation alone (relative risk 0.10, P<0.001). In 558 randomized patients, clinically relevant bleeding occurred in 4.6% vs 5.0% and major bleeding in 1.4% vs 2.2%; intracranial hemorrhage occurred in 2 thrombolysis patients and none on standard care.

    Why it matters: Randomized trial showing a large 7-day benefit of catheter-directed thrombolysis in intermediate-high-risk PE without excess clinically relevant bleeding.

  2. N Engl J Med60

    Timing of PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation.

    In patients with severe aortic stenosis and coronary artery disease undergoing transcatheter aortic-valve implantation (TAVI), doing TAVI before PCI was noninferior to the conventional PCI-first approach. At 1 year, the composite endpoint of death, myocardial infarction, ischemia-driven revascularization, rehospitalization, or major bleeding occurred in 22.2% of the TAVI-first group versus 24.2% of the PCI-first group (risk difference -2.0 percentage points; 95% CI -7.4 to 3.4). This randomized trial of 986 patients at 48 European centers supports resequencing the two procedures.

    Why it matters: It provides randomized evidence on procedural sequencing in a common TAVI population where practice has been unestablished.

  3. JAMA60

    Anticoagulation Monotherapy vs Antiplatelet Monotherapy After Transcatheter Aortic Valve Implant: The ACASA-TAVI Randomized Clinical Trial.

    Oral anticoagulation with a factor Xa inhibitor after transcatheter aortic valve implant reduced leaflet thrombosis compared with acetylsalicylic acid, in a randomized trial of 360 patients aged 65 to 80 with severe aortic valve stenosis. HALT on 12-month 4-dimensional CT occurred in 16.2% of the NOAC group vs 28.6% of the ASA group (risk ratio 0.55; 95% CI 0.37-0.82). The composite safety endpoint of VARC-3 bleeding, thromboembolic events, and all-cause death met noninferiority (7.5% vs 10.6%).

    Why it matters: It compares two monotherapy strategies after TAVI on valve leaflet thrombosis and clinical safety outcomes.

Aug 30Sun
  1. N Engl J Med63

    Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients.

    Clopidogrel monotherapy was noninferior to extended dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin for net adverse clinical events in high-ischemic-risk patients 12 months after drug-eluting stent implantation: 5.0% versus 5.1% at 24 months (risk difference, -0.1 percentage points; 90% CI, -1.3 to 1.2). The trade-off was clear, as the key secondary ischemic end point occurred in 3.7% with monotherapy versus 1.6% with DAPT (hazard ratio, 2.33), while BARC type 2, 3, or 5 bleeding occurred in 1.8% versus 4.1% (hazard ratio, 0.43).

    Why it matters: It shows clopidogrel monotherapy spares bleeding but raises ischemic events in high-risk patients after stenting.

  2. N Engl J Med62

    Prasugrel versus Ticagrelor in Acute Coronary Syndromes.

    A default prasugrel policy did not reduce ischemic events compared with a default ticagrelor policy after percutaneous coronary intervention for acute coronary syndrome. In 17,095 Swedish patients, the composite of death, myocardial infarction, or stroke at 1 year occurred in 11.1% under prasugrel versus 11.8% under ticagrelor (adjusted OR 0.90; 95% CI 0.77 to 1.06), with less major bleeding under prasugrel (4.2% vs 4.4%; OR 0.80).

    Why it matters: Head-to-head registry-based randomized comparison of the two preferred P2Y12 inhibitors in routine care.

  3. JAMA48

    124I-Evuzamitide Positron Emission Tomography/Computed Tomography for Diagnosing Cardiac Amyloidosis: The REVEAL Nonrandomized Clinical Trial.

    124I-evuzamitide PET/CT diagnosed cardiac amyloidosis with 94% sensitivity (95% CI, 85%-98%) and 86% specificity (95% CI, 77%-92%) among 170 adults with suspected disease evaluated at 18 US centers. Positive predictive value was 85% and negative predictive value 94%. The tracer offers a noninvasive test that directly images cardiac amyloid across amyloid types, beyond the transthyretin-restricted approaches currently available.

  4. N Engl J Med72

    Tricuspid-Valve Intervention in Heart Failure.

    Transcatheter tricuspid-valve repair plus medical therapy beat medical therapy alone in patients with symptomatic severe tricuspid regurgitation at high risk of heart-failure events. In 360 randomized patients, the win ratio for the hierarchical composite of death, heart-failure hospitalization, and quality-of-life improvement at 1 year was 2.42 (95% CI, 1.76 to 3.33). Freedom from death or heart-failure hospitalization through 3 years was 52.4% with repair versus 21.0% without (hazard ratio 0.40).

    Why it matters: Randomized evidence that tricuspid-valve repair reduces death and heart-failure hospitalization in severe tricuspid regurgitation.

  5. JAMA59

    Low-Voltage Ablation in Persistent Atrial Fibrillation: The IDEAL-AF Randomized Clinical Trial.

    Adding individualized low-voltage zone ablation to pulmonary vein isolation substantially improved rhythm outcomes in persistent atrial fibrillation patients with low-voltage zones of 3.0 cm2 or greater. In the IDEAL-AF trial, 209 patients at 5 Swedish centers were randomized after pulmonary vein isolation to adjunctive low-voltage zone ablation or no further ablation. Arrhythmia-free survival off antiarrhythmic drugs at 12 months was 67.6% vs 37.4% (odds ratio 3.5; P < .001), with greater quality-of-life gains and no excess serious adverse events.

    Why it matters: First randomized evidence that low-voltage zone-guided ablation improves persistent AF outcomes beyond pulmonary vein isolation.

  6. N Engl J Med69

    Pulmonary Denervation for Heart Failure-Related Pulmonary Hypertension.

    Pulmonary-artery denervation plus guideline-directed medical therapy cut clinical worsening in heart failure-related pulmonary hypertension associated with left heart disease. In 264 randomized patients, the 2-year Kaplan-Meier incidence of clinical worsening was 25.7% with denervation versus 51.5% with medical therapy alone (hazard ratio 0.49, P = 0.006). It offers a procedural option beyond drugs for this population.

    Why it matters: First multicenter randomized trial to show pulmonary-artery denervation reduces clinical worsening in left heart disease-associated pulmonary hypertension.

  7. nature.com59

    Eplontersen with and without background transthyretin stabilizers in transthyretin amyloid cardiomyopathy: secondary analysis of a phase 3, randomized controlled trial

    A secondary analysis of the CARDIOTTRansform phase 3 randomized controlled trial found that eplontersen, a transthyretin-targeting antisense oligonucleotide, benefited patients with transthyretin amyloid cardiomyopathy who were not on transthyretin stabilizers at baseline, but showed no such effect in those already taking stabilizers. The result separates responders from non-responders by background therapy. Findings were presented at the 2026 ESC Congress.

    Why it matters: It identifies baseline transthyretin stabilizer use as a factor determining which cardiomyopathy patients benefit from eplontersen.

Aug 29Sat
  1. N Engl J Med55

    Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event.

    Adding milvexian, an oral factor XIa inhibitor, to standard antiplatelet therapy within 7 days after an acute coronary syndrome did not reduce recurrent ischemic events. In 14,194 patients followed for a median of 12.2 months, the composite of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 5.4% with milvexian versus 5.1% with placebo (hazard ratio, 1.05; 95% CI, 0.91 to 1.21). The trial was stopped for futility at a planned interim analysis; major bleeding rates were 0.3% in both groups.

    Why it matters: A large phase 3 trial shows factor XIa inhibition with milvexian failed to improve outcomes after acute coronary syndrome.

  2. Lancet49

    Safety and efficacy of the 0/1 h pathway for myocardial infarction in the emergency department: an international, pragmatic, stepped-wedge, cluster-randomised, controlled trial.

    Implementing the guideline-recommended 0/1 h troponin pathway was non-inferior to a 0/3 h pathway for the 30-day composite of death from any cause or new type 1 myocardial infarction, meeting the prespecified non-inferiority margin, in 67 624 emergency department presentations with suspected myocardial infarction at 19 hospitals in ten countries. It did not shorten emergency department length of stay, with a median of 309 min in both groups. Faster blood draws alone should not be expected to improve emergency department throughput.

  3. JAMA50

    Pulmonary Vein Isolation Using Pulsed Field Ablation With vs Without Posterior Wall Isolation in Patients With Symptomatic Persistent Atrial Fibrillation: The PIFPAF-PFA Randomized Clinical Trial.

    Adding posterior left atrial wall isolation to pulsed field ablation-based pulmonary vein isolation did not significantly reduce atrial tachyarrhythmia recurrence in persistent atrial fibrillation. Among 206 randomized patients, recurrence by day 91 to 365 occurred in 50.6% with posterior wall isolation vs 60.6% without (RR 0.75; P = .13). Mean atrial arrhythmia burden was lower with posterior wall isolation (6.9% vs 11.0%; P = .04), a secondary finding the authors call hypothesis generating.

  4. JAMA72

    LDL Cholesterol Lowering With Evolocumab Before Percutaneous Coronary Intervention for Acute Myocardial Infarction: The AMUNDSEN Randomized Clinical Trial.

    Evolocumab started in the catheterization laboratory before PCI for high-risk acute MI did not change clinical outcomes at 1 year. All-cause death or unplanned cardiovascular hospitalization occurred in 14.6% of 1087 patients given evolocumab plus standard care vs 15.4% of 1074 given standard care alone (adjusted odds ratio 0.94; P = .59). It did, however, achieve the LDL-C target (<55 mg/dL and at least 50% reduction) in 82% vs 40% of patients at 12 months, with median LDL-C of 16 vs 56 mg/dL at 6 weeks.

    Why it matters: Tests whether immediate PCSK9 inhibition after acute MI affects outcomes, not just LDL-C, in a 2161-patient randomized trial.

  5. N Engl J Med65

    Atorvastatin, Cardiovascular Events, and Disability-free Survival in Older Adults.

    Atorvastatin 40 mg daily lowered major cardiovascular events versus placebo in community-dwelling adults 70 and older without cardiovascular disease, diabetes, or dementia (hazard ratio 0.70, 95% CI 0.61 to 0.82) over a median 5.9 years in the STAREE trial of 9971 participants. It did not extend disability-free survival: death, dementia, or persistent physical disability occurred at similar rates (hazard ratio 0.94, P=0.25). Serious adverse events occurred in 2.7% of each group.

    Why it matters: First trial to test statins for primary prevention and disability-free survival in adults 70 and older.

  6. nature.com62

    Dual antithrombotic therapy using potent antiplatelet inhibitors in atrial fibrillation and acute coronary syndrome: a randomized controlled trial

    Dual antithrombotic therapy combining direct oral anticoagulants with potent P2Y12 inhibitors in patients with atrial fibrillation and acute coronary syndrome was associated with higher bleeding rates than direct oral anticoagulants with clopidogrel and aspirin, with no evidence of reduced ischemic events. The randomized controlled trial results were presented at the 2026 European Society of Cardiology Congress.

    Why it matters: It reports that potent P2Y12 inhibitors increased bleeding without ischemic benefit in this population.

Aug 28Fri
  1. Lancet61

    Safety and lipoprotein(a)-lowering effects of Kylo-11, a non-canonical, long-duration small interfering RNA targeting lipoprotein(a): a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial.

    A single subcutaneous dose of Kylo-11, a very long-acting small interfering RNA targeting lipoprotein(a), cut median serum lipoprotein(a) by up to -97% at 48 weeks in healthy adults with elevated concentrations, with reductions of -53% at 9 mg and -96% in participants above 200 nmol/L given 225 mg. In the 70 dosed participants, adverse events occurred in 53%, mostly grade 1-2 and deemed unrelated; there were no serious or drug-related events. The findings support durable lipoprotein(a) lowering from one dose.

    Why it matters: It shows a single siRNA dose can durably lower lipoprotein(a) for up to 48 weeks in humans.

  2. JAMA59

    Cardiovascular Magnetic Resonance to Guide Defibrillator Implantation for LVEF of 36% to 50%: The CMR GUIDE Randomized Clinical Trial.

    ICD implantation did not reduce the composite of sudden cardiac death or hemodynamically significant ventricular arrhythmia in patients with LVEF of 36% to 50% and CMR-defined myocardial scar. In the randomized trial of 353 patients followed for a median of 6.3 years, the composite occurred in 7.8% with an ICD vs 9.2% with an implantable loop recorder (HR 0.76; 95% CI, 0.37-1.58), though sudden cardiac death alone was lower with ICDs (1.7% vs 5.8%; HR 0.26). A scar-based selection strategy beyond the LVEF 35% cutoff did not change the primary outcome overall.

    Why it matters: It tests whether CMR scar can expand ICD eligibility above the LVEF 35% threshold, a question guidelines leave open.

  3. N Engl J Med60

    Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy.

    Aficamten, a cardiac myosin inhibitor, improved both exercise capacity and symptoms in symptomatic nonobstructive HCM, a condition with no previously proven medical therapy. In the phase 3 ACACIA-HCM trial, 258 patients received aficamten and 259 received placebo; at 36 weeks, peak oxygen uptake differed by a least-squares mean of 0.67 ml per kilogram per minute (P = 0.003) and KCCQ-CSS by 3.0 points (P = 0.02) in favor of aficamten. Reversible ejection fraction reductions below 50% occurred in 10.5% of aficamten patients versus 0.8% on placebo.

    Why it matters: First proven drug therapy for nonobstructive HCM, a common condition with no established treatment.

  4. N Engl J Med57

    Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis.

    Stopping antibiotics early based on clinical response was safe and effective in left-sided infective endocarditis caused by S. aureus, E. faecalis, or streptococcus species. In the POET II trial of 508 stabilized adults, response-tailored therapy gave a median 183 days alive without antibiotics within 6 months versus 169 days with standard 4-to-6-week therapy, and was noninferior for the safety composite (8.2% vs. 10.7%). Relapse of bacteremia or endocarditis was more frequent with tailored therapy (5.1% vs. 1.6%).

    Why it matters: It challenges the consensus of up to 6 weeks of antibiotics for left-sided infective endocarditis with randomized noninferiority data.

Aug 26Wed
  1. JAMA55

    Sodium Bicarbonate for In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

    Sodium bicarbonate did not improve sustained return of spontaneous circulation in adults with in-hospital cardiac arrest. In this double-blind trial at 21 Danish hospitals, 372 patients given up to 100 mmol of sodium bicarbonate and 407 given placebo achieved sustained ROSC at similar rates (39% vs 37%; risk ratio 1.05, P = .62), with no significant differences in 30-day survival or favorable neurologic outcome. The findings do not support routine administration of sodium bicarbonate during in-hospital cardiac arrest, and alkalosis and hypernatremia were more common with it.

    Why it matters: Randomized evidence against a common cardiac arrest intervention that clinicians routinely administer.

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