Investigative Reviews by Tom Nolan — November 24, 2022

  1. Tom Nolan, clinical editor; GP, Surrey
  1. BMJ, London

New hope for lipid profile discussion

Looking for something new to spice up those cholesterol recommendations? Lipoprotein(a) may be what you are looking for. It is considered to be a marker of cardiovascular disease and therefore a candidate for new preventive treatments. A phase 2 dose study examined the effect of olpasiran (which reduces the synthesis of lipoprotein(s) in the liver) on lipoprotein(a) levels. This small study, which enrolled 281 people with established CVD and high lipoprotein(s), did find a dose-dependent reduction in lipoprotein(s) levels in those treated with olpasira. But it’s early: will this reduction translate into clinically meaningful endpoints? Until then, it’s back to the familiar “good and bad cholesterol” and “let’s take a look at your overall risk” chatter.

N Engl J Med doi:10.1056/NEJMoa2211023

Game of the day

The New England Journal of Medicine makes it to the World Cup in football with research from Qatar. Like the World Cup, this cohort study looking at the effects of covid vaccination on children involved a lot of matching: pairing unvaccinated and vaccinated children and waiting to see which of the paired pair scores its own goal of getting covid. Vaccination was found to be associated with modest, rapidly waning protection against the omicron variant in children 5-11 years of age, with only 2.1% of vaccinated children in this age group developing covid during the 110-day follow-up period, compared to 2.4% of unvaccinated controls. There was a greater reduction in the incidence of covid in adolescents, who received the higher 30 μg dose of the BNT162b2 vaccine – but the benefit of vaccination in the pre-omicron cohort was much greater, estimated at 95%, compared to 30% in the omicron Period.

N Engl J Med doi:10.1056/NEJMoa2210058

Ankle replacement or arthritis?

It must be strange to be a participant in the TARVA study, where the decision to have total ankle replacement or arthritis was made with a sophisticated computerized version of a coin toss. It is no wonder that of the 933 people with end-stage osteoarthritis of the ankle who were eligible for the trial at 17 sites in the UK, only 303 agreed to take part. One year after surgery, both groups of patients showed significant improvement in the study’s primary endpoint—the Manchester-Oxford Foot Questionnaire score in the walking/standing domain—but there were no significant differences in these scores between the two groups.

Ann Intern Med doi:10.7326/M22-2058

What goes up must come down

Using 11 variables commonly available in patient records, such as body mass index and blood pressure, researchers were able to create a predictive score that would identify people at higher risk of developing an ascending aortic aneurysm. Their model had a number needed to screen somewhere between 1.8 and 22.8, depending on the cohort tested and the sensitivity threshold. But how many of those diagnosed would actually benefit? A cutoff of 4 cm was chosen as the lower limit of moderate ascending aortic dilatation because it had been used in other studies. However, surgery is not indicated unless aneurysms are much larger (>5.5 cm according to European Society of Cardiology guidelines, with some exceptions such as Marfan syndrome and rapid growth), and there is no effective medical treatment to slow progression – or, as the authors put it, “evidence of effectiveness [of medical treatment] in non-syndromic aneurysms there is still little research.”

JAMA doi:10.1001/jama.2022.19701

Monoclonal antibodies to prevent malaria

Could monoclonal antibodies be effective in preventing malaria? Results from a phase 2 study of CIS43LS, a monoclonal antibody against sporozoites Plasmodium falciparum, showed some promise, but it may still have a long way to go. Laboratory analysis P falciparum infection was used to determine the efficacy of the 330 study participants in Mali – clinical malaria episodes were not recorded. The higher dose of the two studied was 88% effective at six months compared to placebo. Further research will tell us how this translates into prevention of clinical malaria, but the need for a 30-minute intravenous infusion may limit its potential for widespread use.

N Engl J Med doi:10.1056/NEJMoa2206966


  • Competing interests: None declared.

  • Provenance and peer review: Not commissioned, not peer reviewed.

Leave a Comment

Your email address will not be published. Required fields are marked *