Tom Nolan’s research reviews—23 March 2023

Target practice

NICE recommends that we prescribe atorvastatin 80 mg for secondary prevention of cardiovascular disease. An open-label randomised trial set in Japan asked whether a treat-to-target approach starting with a moderate intensity statin dose may be as effective as a high intensity dose for preventing death, myocardial infarction, stroke, or coronary revascularisation at three years in people with coronary artery disease. The treat-to-target approach—where the dose of statin is titrated to low density lipoprotein cholesterol (LDL-C) levels—was found to be non-inferior to a fixed dose of atorvastatin 40 mg or rosuvastatin 20 mg. Although the study found the primary outcomes from the two approaches were similar, the treat-to-target approach seems to be more resource intensive (needing more blood tests and appointments for titrating doses). Only 60% of the treat-to-target group achieved their target level of LDL-C.

JAMA doi:10.1001/jama.2023.2487

Active monitoring of prostate cancer trial continues

The headline news from the latest publication from the Prostate Testing for Cancer and Treatment (ProtecT) trial is that, after 15 years, there was no difference in prostate cancer-specific mortality in men found to have localised prostate cancer after PSA screening, regardless of whether they were randomised to active monitoring, prostatectomy, or radiotherapy. There’s a striking figure in this paper that shows how prostate cancer-specific survival stayed close to 100% for the whole 15 year follow-up, only falling to around 97% in each arm of the trial.

Active monitoring didn’t mean no radical therapy, however: by 10 years, around half of patients had received radiotherapy or prostatectomy. Advances in treatments for metastatic disease likely contributed to the finding that 86% of those in the active monitoring group diagnosed with metastasis at 10 years survived to 15 years. The study’s authors conclude that men with newly diagnosed localised prostate cancer can take the time needed to consider each of these treatment options in relation to their own circumstances, values, and preferences.

N Engl J Med doi:10.1056/NEJMoa2214122

Non-hormone options for vasomotor symptoms

Non-hormone based medication for vasomotor symptoms as a result of the menopause can include selective serotonin reuptake inhibitors (SSRIs), clonidine, and the prescriber’s version of clutching at straws—gabapentin. Might the neurokinin-3 receptor antagonist fezolinetant offer a more effective option? A phase 3, placebo controlled trial shows promise, in women with seven or more moderate to severe hot flushes a day. Those randomised to receive fezolinetant 30 mg once daily experienced a reduction in the number of hot flushes from an average of 10.7 to 4.5 per 24 hours after 12 weeks (versus a reduction from 10.5 to 6.9 per 24 hours in the placebo group). As ever, more studies are needed to establish the drug’s long term efficacy and safety.

Lancet doi:10.1016/S0140-6736(23)00085-5

In the loop

A study of a closed loop insulin system in children aged between 2 and 6 years old with type 1 diabetes opened my eyes to how challenging it must be to manage. Not only are kids at this age unpredictable in what they eat—from my experience, a mealtime could be over after anything from a few peas to four helpings of pasta—but their insulin requirements are apparently small, making dosing difficult. Unsurprisingly, perhaps, many children in this age group have blood glucose levels above their target range. Children in the closed loop system arm of the study, in which an insulin pump adjusts insulin delivery in response to continuous glucose monitoring, saw an average increase in the time that glucose levels were within the target range of about 3 hours a day (from 57% to 69%), whereas those in the control group (standard care) didn’t see any meaningful improvement in this measure (55% to 56%).

N Engl J Med doi:10.1056/NEJMoa2210834

Chair pose

I’m not one for eavesdropping on people’s conversations, but whenever I do happen to overhear what people talk about—in a cafe or at the school gate, for instance—they’re usually talking about when they last saw their GP. And often not in a good way: “I went to the doctor about my back, and they just told me to do some yoga.” I’ve made many a misjudged or mistimed suggestion to try a non-medical approach and no doubt have been the subject of many such conversations.

A systematic review of randomised controlled trials of yoga based interventions on measures of frailty gives some more evidence to keep going. It found moderate certainty evidence that yoga improved gait speed, lower extremity strength, and endurance compared with education or inactive controls. For yogis out there, most of the studies used hatha yoga and Iyengar or chair-based methods.

Ann Intern Med doi:10.7326/M22-2553