Ann Robinson’s research reviews—20 November 2020

Ann Robinson reviews the latest research from the top medical journals

A new equation for measuring kidney function

Estimates of glomerular filtration rate (eGFR) use equations based on serum creatinine, but they don’t account for transitions from adolescence to adulthood, resulting in overestimation of GFR in young adults. A full age spectrum (FAS) equation has addressed this anomaly, but still overestimates GFR when serum creatinine levels are low. This study found that a new equation (EKFC) was more accurate than other commonly used equations. It’s not perfect; like all creatinine-based GFR estimation equations, EKFC overestimates GFR in people with low muscle mass. Adding an equation based on cystatin C, which isn’t as influenced by muscle mass, to EKFC would enhance the accuracy. A major limitation is that this Swedish study did not have any black participants. It will need to be tested in more diverse populations before being widely adopted.

Ann Intern Med doi:10.7326/M20-4366

Rivaroxaban for valvular atrial fibrillation?

Warfarin monitoring and dose adjustment can be tricky at the best of times, and covid-19 restrictions haven’t helped. Most of our patients who need anticoagulation, usually because they have non valvular atrial fibrillation, are already taking an oral agent such as rivaroxaban rather than warfarin. Until now, however, guidance has said that those with an artificial heart valve must remain on warfarin. This helpful, though small, randomised study found that rivaroxaban was non-inferior to warfarin in patients with atrial fibrillation and a bioprosthetic mitral valve in terms of death from cardiovascular or thromboembolic events (3.4% v 5.1%), stroke (0.6% v 2.4%), or major bleeding (1.4% v 2.6%) at 12 months. The trial had some limitations: the open-label design may have introduced some bias, and the findings can’t be extrapolated to bioprosthetic aortic valves, mitral stenosis, or mechanical valves. Trials are under way in these other groups.

N Engl J Med doi:10.1056/NEJMoa2029603

A daily polypill and aspirin is no panacea

This complicated study randomly assigned people with a raised risk of heart disease (using INTERHEART score), but no overt signs, into three paired groups, each matched with its own placebo control: those given a daily polypill (simvastatin, atenolol, hydrochlorothiazide, and ramipril), daily aspirin, or monthly vitamin D. The impact of adding aspirin to the polypill was also measured. The results were underwhelming: the polypill-aspirin combination reduced events (death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularisation) in those at intermediate risk of cardiovascular disease compared with placebo by a modest amount (4.1 v 5.8%) after a mean follow-up of 4.6 years. Other risk groups or interventions didn’t show significant benefit, and the polypill was associated with more reported dizziness and hypotension. The authors wonder whether their results underestimate the true effect of a polypill and aspirin because of the high rate of discontinuation (unrelated to side effects), drug supply problems, and the impact of covid-19. Wishful thinking perhaps.

N Engl J Med doi:10.1056/NEJMoa2028220

Clopidogrel remains the standard for elective percutaneous coronary intervention

Platelet inhibitors prasugrel and ticagrelor seem to work better and faster than clopidogrel in acute coronary syndrome. However, clopidogrel remains the standard in patients with stable coronary disease undergoing elective percutaneous coronary intervention (PCI). This study found that, although ticagrelor showed higher levels of platelet inhibition than clopidogrel, there was no reduction in myocardial infarction or injury within 48 hours of high risk PCI in stable coronary patients, and no significant difference in 30 day outcomes. Analysis of a previous study (stopped prematurely because of problems with enrolment) that compared prasugrel with clopidogrel showed similar results; more potent platelet inhibition didn’t translate into clinical benefit. On the plus side, prasugrel and ticagrelor didn’t cause more major bleeds than clopidogrel, but that’s not enough to change practice. The open-label design of this trial meant a risk of inherent biases, hard clinical outcomes were difficult to determine, and half the study population was already on long term clopidogrel, which might have blunted the effect compared with ticagrelor. For now, however, clopidogrel remains the treatment of choice for stable coronary patients undergoing elective PCI.

Lancet doi:10.1016/S0140-6736(20)32236-4

An antidepressant that may help with covid-19? Too early to say

This small, preliminary randomised trial found that fluvoxamine, an SSRI antidepressant and σ-1 receptor (S1R) agonist, seemed to reduce clinical deterioration in outpatient covid-19 patients compared with placebo. S1R agonism has a modulatory effect on the immune system, which explains the interest in fluvoxamine in this setting. A larger trial with more defined outcomes and longer follow-up is needed before any claims can be made. This population was relatively young (mean age 46 years), female (72%), and not seriously unwell (not needing hospitalisation and oxygen saturation >92%). The study was more interesting for being a fully remote (contactless) study of self quarantining adults, which was handy for participants but required a vast amount of staff time to organise.

JAMA doi:10.1001/jama.2020.22760

Ann Robinson is an NHS GP and health writer and broadcaster