Knees, cholesterol and an AI ECG: what four new trials showed

In 445 adults with knee osteoarthritis and excess weight, an experimental weekly injection eased pain and cut weight by about a fifth

On 8 November 2026 the New England Journal of Medicine published the knee osteoarthritis results of retatrutide, an experimental once-weekly injection that acts on three hormone receptors at once: GIP, GLP-1 and glucagon. In TRIUMPH-4, 445 adults with painful knee osteoarthritis and obesity or overweight were randomly assigned to retatrutide 9 mg, 12 mg or placebo for 68 weeks. A second, prespecified group of 574 people with knee osteoarthritis and obesity was enrolled within the larger TRIUMPH-1 trial and followed for 80 weeks.

In TRIUMPH-4, according to the developer, knee pain on the WOMAC pain scale fell by about 4.0 points on 9 mg and 3.7 points on 12 mg, against 2.1 points on placebo, and body weight fell by 20.0% and 23.7%, against 4.6%. In the TRIUMPH-1 group, whose average pain score at the start was about 6, pain fell by 3.66, 4.19 and 4.30 points on 4, 9 and 12 mg, against 2.24 points on placebo, at week 80, and weight fell by 18.6% to 28.7%, against 1.5%. Gastrointestinal effects were the most common adverse events.

Pain also eased noticeably on placebo, and the trials were not designed to separate the effect of weight loss from any direct effect on the joint. Retatrutide is an investigational phase 3 medicine and is not approved for clinical use; the trials were funded by its developer, Eli Lilly.

In 3048 people with heart and artery disease, starting a statin with ezetimibe did not lower events more than a statin alone

On 7 November 2026 Circulation published a prespecified second randomisation of the Ez-PAVE trial, run at 17 centres in South Korea. All 3048 participants had atherosclerotic cardiovascular disease and were already being treated to an LDL cholesterol target, either below 55 or below 70 mg/dL (1.4 or 1.8 mmol/L). On top of that, half started on two long-approved cholesterol-lowering medicines at once, a statin plus ezetimibe, and half started on a statin alone; treatment was then adjusted by a set protocol to reach the target. Mean age was 64.4 years and 20.9% were women.

Over three years the combined outcome of cardiovascular death, heart attack, stroke, any revascularisation or hospital admission for unstable angina occurred in 8.5% of people who started on the combination and 7.9% of those who started on a statin alone (hazard ratio 1.07; 95% CI 0.83 to 1.37). The combination did reach lower LDL: a median of 53 versus 62 mg/dL in the lower-target group and 63 versus 70 mg/dL in the conventional-target group. Safety outcomes were similar.

Both drugs are long approved, so this is a test of strategy, not of a new medicine. The study was open-label, and ezetimibe was eventually added for 34.3% and 24.8% of the statin-first patients in the two target groups, which reduced the separation between the two starting strategies. Three years of follow-up do not show whether the gap in LDL would change event rates over a longer period.

In 14,665 adults, AI-guided ECG monitoring found slightly more early heart rhythm problems, but the result hangs on a single event

On 7 November 2026 Circulation published LATENT, a single-centre, open-label randomised trial of an artificial intelligence model that reads ordinary 12-lead ECGs recorded in normal sinus rhythm and flags ECGs at high risk of atrial fibrillation for targeted rhythm monitoring. A total of 14,665 adults aged 40 to 85 with no known atrial fibrillation or flutter were assigned to AI-guided monitoring or usual care. People the AI marked as high risk were offered a Holter monitor for up to 7 days, and each was matched to a control of the same age and sex who received the same monitoring.

The AI marked 1.1% of each group as high risk. Within 90 days, new atrial fibrillation, atrial flutter or early warning rhythms were found in 0.74% of the AI group versus 0.48% of controls (odds ratio 1.54; 95% CI 1.01 to 2.37; P = 0.046). Among high-risk people the difference was large, 32.1% versus 2.6%; among low-risk participants it was 0.4% versus 0.5%. Atrial fibrillation or flutter on its own was found in 0.3% versus 0.2%, and the start of rhythm-control drugs by 180 days did not differ.

The authors themselves call the result statistically fragile: reclassifying one event would move the P value to 0.057. Only 57% of high-risk people agreed to monitoring, and skin reactions or discomfort from monitoring were reported by 22.9% of monitored participants in the AI group and 18.8% of matched controls. The trial counted detections, not strokes or deaths, so it does not show that AI-ECG screening improves health.

After a single infusion of either of two experimental antibodies, clots linked to arm catheters fell from 43% to 20% in a phase 2 trial

On 7 November 2026 The Lancet Haematology published ROXI-CATH, a double-blind, placebo-controlled phase 2 trial in 12 hospitals in Bulgaria, Canada, Israel, Romania, the UK and the USA. It tested two experimental monoclonal antibodies against clotting factor XI, amrecibart and cenvacibart, given once intravenously, in 195 adults who were having a peripherally inserted central catheter (PICC), a thin line placed through an arm vein, expected to stay in for at least 14 days. No drug is approved to prevent clots around these catheters.

By day 14, adjudicated venous thromboembolism, including catheter-linked thrombosis with or without symptoms and pulmonary embolism, occurred in 20% of people on either antibody, against 43% on placebo (odds ratios 0.37 and 0.36). Nobody had major bleeding up to day 14, and clinically relevant non-major bleeding occurred in 3% of each group. Serious adverse events occurred in 14% on amrecibart, 9% on cenvacibart and 16% on placebo.

Ultrasound was scheduled on days 7 and 14, so the main outcome counted clots without symptoms as well as those with them. The trial randomised 195 people, assessed the main outcome only to day 14, and 99% of participants were white. Both antibodies are experimental and not approved; the trial was funded by their developer, Regeneron. Whether blocking factor XI prevents clots without raising bleeding risk will need larger trials with clinical outcomes.

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

• Schnitzer TJ, Hunter DJ, Conaghan PG, Sharma AM, et al. Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity. N Engl J Med. 2026. doi:10.1056/NEJMoa2610676, NCT05931367, NCT05929066

• Eli Lilly and Company. Press release on the TRIUMPH-4 phase 3 results of retatrutide. Press release

• Three Doses of Once-Weekly Retatrutide in Adults with Knee Osteoarthritis and Obesity: An 80-Week Phase 3 Randomized Clinical Trial. ACR Convergence 2026 abstract. ACR abstract

• Lee SH, Byun YS, Kim JW, et al. Statin-Ezetimibe Combination Therapy versus Statin Monotherapy in Atherosclerotic Cardiovascular Disease: A Prespecified Secondary Analysis of the Randomized Ez-PAVE Trial. Circulation. 2026. PMID 42998308, doi:10.1161/CIRCULATIONAHA.126.083811, NCT04626973

• Lee CC, Lin WY, Liu WT, et al. Leveraging AI-ECG Technology for Early Notification and Tracking of AF Development (LATENT): A Randomized Controlled Trial. Circulation. 2026. PMID 42998297, doi:10.1161/CIRCULATIONAHA.126.083540, NCT06847932

• Zwicker JI, Kithcart AP, Kaplan J, et al. Amrecibart and cenvacibart for the prevention of catheter-related thrombosis (ROXI-CATH): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Haematol. 2026. PMID 42998669, doi:10.1016/S2352-3026(26)00249-8, NCT06299111