Alex Nowbar reviews the latest research from the top medical journals.
Annals of Internal Medicine
A trial of recommending mask use
The DAN-MASK trial randomised thousands of people in Denmark during the first wave to one of two sets of recommendations. Note, that they weren’t randomised to mask or no mask. The recommendations were either social distancing only or social distancing with masks (with a pack of 50 masks thrown in for that group). Both groups could use masks if they wanted. SARS-CoV-2 rates in the former were 2.1% and 1.8% in the latter and this difference was not statistically significant. This means the additional advice to use masks in that group of participants, at that time, in that setting, did not reduce infection rates. Social distancing was already in place, compliance and follow-up were imperfect, and infection rates weren’t that high. So these data tell us little about the effect of masks themselves. This does not denigrate the trial though. It’s just important to be clear about what the trial did and did not test and what we can therefore take away from it.
Fish oil for the heart
This question keeps coming back. Kalstad et al. randomised over a thousand people with myocardial infarction aged 70 to 82 to n-3 polyunsaturated fatty acids (PUFA) or a corn oil placebo in a double-blind fashion. They call this a trial of older people even though I’d consider this age group not that old, but for trial participation I suppose it is relatively old. There was no difference between groups in the primary endpoint of MI, death, revascularisation, stroke and heart failure hospitalisation at two years. There was a hint at more atrial fibrillation in the PUFA group compared to control. These data do not support use of this supplement for cardiovascular protection. This is in contrast to similar supplements that have been shown to be protective. The jury is still out I think.
AF ablations reduce AF
Ablation for atrial fibrillation is long-standing big business for cardiologists and yet, how best to realise the potential benefits is still subject to much debate. EARLY-AF is a Canadian randomised trial of ablation versus drugs looking at the effect on the rhythm using an implantable cardiac monitor. The rate of recurrence of atrial tachyarrhythmia at one year was 42.9% in the ablation group and 67.8% in the drug group. This is a very significant lowering and supports claims of efficacy of the procedure. Also, adverse events were very rare (although real world outcomes might be different as trial conditions and trials patients are a different kettle of fish). Should ablation therefore be used early on instead of current guideline recommendations for a trial of drugs first? Quite probably, yes, although it doesn’t change results of much larger previous studies that stroke and death risk aren’t reduced by ablation. The main caveats of this trial are lack of blinding meaning that groups could have been differentially treated after randomisation e.g. use of medications, and that one ablation technique was used so the results may not be replicated by other techniques. Lack of blinding particularly calls into question the symptomatic benefit observed as a secondary endpoint.
Another SGLT2 inhibitor
Sanofi/Lexicon Pharmaceuticals tested their SGLT2 inhibitor, sotagliflozin, in two large randomised trials, SCORED for people with diabetes and SOLOIST for people with diabetes and recent worsening heart failure. SCORED stopped early due to covid-19-related loss of funding, but still found a reduction in hospitalisations and urgent visits for heart failure. However, the adverse events were not encouraging: “Diarrhoea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo.” SOLOIST found that sotagliflozin initiated before or shortly after discharge reduced deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure compared to placebo. Again the adverse events were not encouraging but these data do support the overall class effect of SGLT2 inhibitors. I think I’d want dapa or empa long before sota though.
Recurrent pericarditis is challenging to treat; all we really have is colchicine. RHAPSODY was a double-blind randomised trial of a new drug, rilonacept given once a week subcutaneously, in 61 patients. Rilonacept is an Interleukin-1 trap which sounds pretty epic since IL-1 is implicated in so many inflammatory processes. You may feel 61 is a small sample size, but the trial ran until the pre-specified number of post-randomisation events had occurred as required by their power calculation for demonstrating efficacy. They found that rilonacept was associated with a significantly lower risk of pericarditis recurrence than placebo which is great news for affected patients. The methods indicate that “The sponsor directed all aspects of the trial, held the data, and performed the statistical analyses.” They go on, “The academic research organization C5Research provided independent confirmation of the trial analyses.” This seems reasonable. There is huge potential conflict of interest, but we have not been given a reason not to accept the trial’s conclusions.
Alex Nowbar is a clinical research fellow at Imperial College London, UK.
Competing interests: none declared.