Alex Nowbar reviews the latest research from the top medical journals

Annals of Internal Medicine

Coaching for weight maintenance

Conroy et al examine the role of coaching in weight management in a randomised controlled trial of 194 participants who had intentionally lost at least 5% of their body weight in the last two years. They also threw in a bit of electronic health records for good measure. The study arms were: tracking via electronic health records versus the same plus coaching. So really its a trial of a two year coaching programme. Good news, at two years weight regain in the coaching group was lower (2.1kg vs 4.9kg in the tracking only group). Those in the coaching group were more likely to maintain weight loss of at least 5%. The coaching was in the form of personalised health coaching through the electronic health record patient portal, with intensive initial contact (weekly for a month) that tapered off over the two years. The electronic health record served as an important part of the control for those in the tracking group because it was used to send the tracking participants questionnaires on general health. This was a well designed study of an interesting intervention format i.e. an electronic health record-based lifestyle intervention.

JAMA

Bempedoic acid for reducing LDL Cholesterol

If you name a trial CLEAR Wisdom, you should be prepared to be accused of being smug. But perhaps Esperion Therapeutics should be. Bempedoic acid was tested in a double-blind randomised controlled trial of 779 people with high cardiovascular risk and raised LDL-C despite maximally tolerated lipid-lowering therapy. At 12 weeks, it reduced LDL-C levels dramatically compared to placebo and was reasonably well-tolerated and safe. Its now ready for the next stage of clinical trials to establish the impact on cardiovascular outcomes. There are a number of players on this stage though, PCSK-9 inhibitors in particular. In fact there are a spate of new cardiovascular drugs making an appearance and each ones glory is being somewhat diluted by the others. It is therefore unclear which will become commonly prescribed and which will fall by the wayside. Unfortunately I suspect it will be marketing and trendiness that determines how this plays out because the head-to-head data is unlikely to come soon.

Lancet

Hope for NASH

Thyroid hormone analogue, resmetirom, is an oral drug for treatment of NASH fibrosis. Harrison et al tested it in a double-blind Phase 2 randomised controlled trial of 125 patients in the US. Naturally, drug-makers, Madrigal, were closely involved in this studys design and analysis. They found it reduced hepatic fat at 12 weeks as measured by MRI proton-density fat fraction. As well as singing the praises of this new drug, this study highlights the utility of this non-invasive measure of hepatic fat as opposed to biopsy which is not practical for serial monitoring. There were also significant lipid profile improvements with resmetirom compared to placebo. However all the efficacy outcomes assessed in this study were biomarkers not actual outcomes so the clinical benefits are not yet known. But these data are promising and certainly confirm that the thyroid hormone pathway has an important role in NASH fibrosis.

Steroids for the DIPs and PIPs

I hate to stereotype, but Dutch trials are often particularly robustly designed, like this double-blind randomised controlled trial of 6 weeks of prednisolone 10mg once daily versus placebo. The inclusion criteria are important here. Participants had to have symptomatic hand osteoarthritis with signs of inflammation in their distal and proximal interphalangeal joints. Objective evidence was required, including osteoarthritis nodes, swelling, or erythema and synovial thickening on ultrasound. And the inclusion criteria even went one step further to require finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug washout (defined as worsening of finger pain by at least 20 mm on the VAS). The primary endpoint of finger pain improvement on the VAS at 6 weeks was positive with a large effect size with no adverse safety signal. These data are extremely useful for those with this condition, but it sounds like itll be in the rheumatologists domain for now. The inclusion assessment appears too strict to be feasible in primary care.

JAMA Internal Medicine

Testosterone and thromboembolic risk

It seems obvious that testosterone therapy should be used only to treat hypogonadism and even then it should not be taken lightly. It has previously been linked to higher risk of heart attack or stroke. This large US observational study of men with deep vein thrombosis or pulmonary embolism (but without a cancer diagnosis) found an association between short-term testosterone therapy and increased risk of a thromboembolic event. The study design was interesting as each individual acted as their own control by examining them 6-12 months before the thromboembolic event while the 6 month period before the event was considered the case period. Other key findings were that thromboembolic risk was highest in the first 3 months after starting testosterone therapy, that route of testosterone made no difference to the risk and that the risk was present in men with or without hypogonadism.

NEJM

Apple watch rhythm notifications

Can an Apple watch detect atrial fibrillation? Probably. 419,297 young people participated in this study. They were monitored for a median of 117 days. An irregular rhythm was flagged in 0.52% of them (3% in the over 65s). These people got sent an ECG patch to wear for 7 days. Of those, only 21% returned the patch to the researchers. Of those who returned the patch, a third had documented atrial fibrillation. There is no comparator group to know whether the incidence of detected atrial fibrillation would have been similar without using the watch. And there was huge potential for selection bias, for example people who felt symptomatic might have been more likely to participate (so these data represent a skewed population) and people with more irregular rhythm periods and/or more symptoms might have been more likely to return the patch (again skewing the data). These bias issues are the reason studies arent conducted in this manner. This study design neither answers the question it says it set out to answer, nor provides clinically relevant evidence.

The new and improved smallpox vaccine

Pittman et al compared two doses of a new smallpox vaccine called modified vaccinia Ankara (MVA) to an existing vaccine (only requiring one dose) in an open-label randomised controlled trial of 440 people. They were looking for non-inferiority in peak antibody titres and the so-called take reaction which were both assessed in a blinded fashion. It is prudent but alarming that we are preparing our defences against a disease that has supposedly been eradicated. But there could be another outbreak one day. The existing vaccine is effective but carries fairly significant risks and hence the need for something better. MVA won the day with respect to equivalent efficacy and fewer serious adverse events. But do these efficacy endpoints (antibodies and the take) really reflect the protection this vaccine provides? And how long would the protection last? Who knows.

Colchicine after myocardial infarction

The inflammatory hypothesis in atherosclerosis has been bubbling away for many years. COLCOT is the first study that practically applies this with a degree of success. COLCOT was a double-blind randomised controlled trial of colchicine 500mcg once daily versus placebo for cardiovascular risk reduction after an MI. Colchicine started within 30 days of the MI was found to reduce cardiovascular events at 2 years, and surprisingly without substantially increasing diarrhoea rates. The cardiovascular event reduction was mainly driven by fewer strokes and fewer revascularisations for angina though which is a bit disappointing since MI and death prevention is what we were really hoping for. Colchicine for prevention of need for revascularisation doesnt even really make sense because there are plenty of other anti-anginal therapies. Arguably this event shouldnt have been part of the primary endpoint. Overall, there are benefits of colchicine that can justify its use but will patients really find it worth the hassle given all the other medications they get given (and often dont adhere to) after an MI?

Alex Nowbar is a clinical research fellow at Imperial College London

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Alex Nowbar's weekly review22 November 2019 - The BMJ - The BMJ

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