Less after a heart plug, more against pancreatic cancer: a digest of four

In 1,857 people with atrial fibrillation, aspirin alone after appendage closure was no worse than two antiplatelet drugs

On 2 November 2026 JAMA published SIMPLAAFY, an open-label randomised trial at 87 US sites in 1,857 people with atrial fibrillation not caused by valve disease who had undergone a successful left atrial appendage closure. Mean age was 76 and 42.9% were women. After the procedure antithrombotic drugs are given to allow time for tissue to cover the device, and the best regimen for this period was unknown.

Participants were assigned to one of three regimens: two antiplatelet drugs for 6 months and then aspirin (624 people), a reduced-dose oral anticoagulant for 3 months and then aspirin (620), or aspirin alone for 12 months (613). At 6 months the combined outcome of death, stroke, systemic embolism or major bleeding occurred in 6.9%, 5.1% and 3.3% respectively. Both simpler regimens met the pre-set criterion for being no worse than the two-drug regimen. Major bleeding occurred in 4.5%, 2.7% and 1.7%.

The trial was open-label, lasted 6 months and was designed to show "no worse", not "better"; bleeding and clots on the device (3.4%, 0.9% and 2.7%) were exploratory outcomes without adjustment for multiple comparisons. The results apply to people after an uncomplicated procedure who could take any of the three regimens. Several authors are employees of Boston Scientific.

In a phase 2 trial of 392 people with pancreatic cancer, adding an immune drug to chemotherapy improved event-free survival

On 2 November the Journal of Clinical Oncology published a randomised phase 2 trial led from Zhejiang University in Hangzhou, China, in 392 people with borderline resectable or locally advanced pancreatic cancer. Participants were randomly assigned to modified FOLFIRINOX chemotherapy alone or combined with toripalimab, which blocks the PD-1 protein.

After a median follow-up of 39.6 months, median event-free survival was 11.1 months with the combination and 9.6 months with chemotherapy alone (hazard ratio 0.74; 95% CI 0.60 to 0.92). Median overall survival was 20.6 versus 17.1 months, but this difference was not statistically significant (hazard ratio 0.81; 95% CI 0.63 to 1.03). Tumours shrank more often with the combination (30.1% vs 18.9%), while the share of patients who had their tumour removed was similar (42.3% vs 43.9%). Severe adverse events occurred in 47.9% and 49.2%.

This is an open-label phase 2 trial from one country. Prespecified subgroup analyses suggested better event-free and overall survival in borderline resectable but not in locally advanced cancer; these findings need confirmation.

In 592 people with heart failure on modern treatment, an old drug pair did not change the main outcome

On 4 November the European Heart Journal published H-HeFT, a double-blind placebo-controlled trial at 23 Danish hospitals in 592 people with heart failure and a left ventricular ejection fraction of 40% or less who were already on contemporary treatment. Median age was 72, 18% were women and most participants were White. They received hydralazine with isosorbide dinitrate, a combination that had shown benefit in earlier randomised trials, or placebo, and were followed for a mean of 3.7 years.

The main outcome, a composite of hospital admission for worsening heart failure, an urgent visit requiring intravenous treatment, heart transplantation, a left ventricular assist device or death, occurred in 30.6% with the combination and 30.5% with placebo (hazard ratio 0.90; 95% CI 0.67 to 1.21; P = .48). Worsening heart failure events occurred in 52 and 47 patients.

There were fewer deaths with the combination, 57 versus 72, but the confidence interval crosses no effect (hazard ratio 0.72; 95% CI 0.51 to 1.02), and as a secondary outcome this cannot be read as a benefit. Most participants were men and predominantly White.

The UK extended a gene-editing treatment for two inherited blood disorders to eligible children from age five

On 30 October the UK medicines regulator, the MHRA, announced that it had extended the authorisation of exagamglogene autotemcel (Casgevy, Vertex) on 29 October to children aged five and over with severe sickle cell disease or transfusion-dependent beta-thalassaemia who meet the eligibility criteria. Previously it was authorised in the UK from age 12.

In both disorders a gene error disrupts haemoglobin, the protein red blood cells use to carry oxygen. In beta-thalassaemia patients often need a blood transfusion every 3 to 5 weeks. The treatment uses the patient's own bone marrow stem cells: they are collected, edited in a laboratory so that the body produces functioning haemoglobin, and infused back after conditioning treatment that prepares the bone marrow. A hospital stay may follow while the cells settle. About 15,000 people in the UK have sickle cell disorder.

The announcement gives no efficacy or safety figures for children aged 5 to 11; the MHRA says the product information will be published within 7 days of approval. The side effects it names are nausea, fatigue, fever and an increased risk of infection.

This article is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.

Sources

• Reddy VY, Saliba WI, Waggoner T, et al. Antithrombotic Therapy After Left Atrial Appendage Occlusion: The SIMPLAAFY Randomized Clinical Trial. JAMA. 2026. PMID 42970643, doi:10.1001/jama.2026.21361, NCT06521463

• Bai X, Li X, Chen Y, et al. Immunochemotherapy for Borderline Resectable or Locally Advanced Pancreatic Cancer: A Randomized Controlled Trial. J Clin Oncol. 2026. PMID 42970668, doi:10.1200/JCO-26-01393

• Køber L, Skak-Hansen KW, Larsen AH, et al. Hydralazine-isosorbide dinitrate in chronic heart failure with reduced ejection fraction: the H-HeFT trial. Eur Heart J. 2026. PMID 42978512, doi:10.1093/eurheartj/ehag773

• MHRA. MHRA approves gene-editing treatment for children aged five and over with serious inherited blood disorders. Press release, 30 October 2026. gov.uk