JC: Aspirin is not effective for hospitalised COVID19 patients. St Emlyn’s

We’ve reported on the RECOVERY trial several times already on the blog. It stands out as the most important trial of therapeutics in hospitalised patients with COVID19.

This week the RECOVERY trial has released the first results from the Aspirin arm of the trial. We await the peer reviewed paper, but we are already very familiar with the trial and it’s processes having reported the results on the blog already. We are therefore pretty confident about the methodology.

To briefly summarise the trial so far

Eligibility: Hospitalised patients with COVID19.

Principle Outcome: 28 day mortality

Aspirin was removed from the trial about 6 weeks ago, with the results coming out today.

To quote the RECOVERY team

The RECOVERY trial was established as a randomised clinical trial to test a range of potential treatments for patients hospitalised with COVID-19. Patients with COVID-19 are at increased risk of blood clots forming in their blood vessels, particularly in the lungs. Between November 2020 and March 2021, the RECOVERY trial included nearly 15,000 patients hospitalised with COVID-19 in an assessment of the effects of aspirin, which is widely used to reduce blood clotting in other diseases.

RECOVERY TRIAL TEAM

In terms of the results then the trial has reported the following through press release on the main trial website. As always we need to be cautious about interpreting data based on a press release, but as we have previously seen the trial methodology in a number of previous publications we are confident that the trial is well designed and delivered.

A total of 7351 patients were randomised to aspirin 150 mg once daily and compared with 7541 patients randomised to usual care alone. There was no evidence that aspirin treatment reduced mortality. There was no significant difference in the primary endpoint of 28-day mortality (17% aspirin vs. 17% usual care; rate ratio 0.96 [95% confidence interval 0.89-1.04]; p=0.35). The results were consistent in all pre-specified subgroups of patients.

Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1·06; 95% CI 1·02-1·10; p=0·0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who progressed to invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·96; 95% CI 0·90-1·03; p=0·23). For every 1000 patients treated with aspirin, approximately 6 more patients experienced a major bleeding event and approximately 6 fewer experienced a thromboembolic (clotting) event.

RECOVERY TRIAL TEAM

So the findings suggest no benefit in terms of the primary outcome of mortality and no real benefit in terms of thromboembolism vs. major bleeding (secondary outcomes). On this basis we cannot recommend Aspirin as a treatment for hospitalised COVID19 patients.

As ever there are a few caveats. We must remember that RECOVERY is an open label trial and at the moment we only have results up to the 28-day point (further analyses at 6 months will eventually be available). However, the margins seen in this trial result make the likelihood of any meaningful difference very unlikely indeed.

This afternoon the pre-print of the paper has gone up on the MedRxiv server.

What is very reassuring is the difference in mortality in this cohort as compared to the first trial results seen in June last year when we first learned of the benefits of Dexamethasone. Back in June last year the mortality for trial patients was 24% in the usual care group. In this cohort mortality is 17%. So, in a year we have probably reduced mortality by 7%. That is truly remarkable and something that all of us involved in the care and research of COVID19 should be proud of.

In the sub group analyses there are some interesting findings. The aspirin group had a shorter hospital stay (8 vs 9 days). In addition there was a statistically greater likelihood of being discharged alive in the aspirin group within 28 days (75% 238 vs. 74%, rate ratio 1·06, 95% CI 1·02 to 1·10, p=0·0062).

Where next?

Sadly it looks as though we are at risk of another wave of cases in the UK. In the last week I’ve seen a real uptick in the number of terrible looking COVID19 chest X-rays in the ED. Alarmingly they are predominantly in the younger aged patients, presumably because they are less likely to have been vaccinated. It does mean that COVID19 is far from beaten in my part of the world and we must remain vigilant in our clinical assessment and in our use of PPE.

vb

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References

  1. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. https://www.medrxiv.org/content/10.1101/2021.06.08.21258132v1.full.pdf
  2. RECOVERY trial closes recruitment to colchicine treatment for patients hospitalised with COVID-19 https://www.recoverytrial.net/news/recovery-trial-closes-recruitment-to-colchicine-treatment-for-patients-hospitalised-with-covid-19
  3. Simon Carley, “JC: RECOVERY trial shows Tocilizumab effective for COVID19. St Emlyn’s,” in St.Emlyn’s, February 11, 2021, https://www.stemlynsblog.org/jc-recovery-trial-shows-tocilizumab-effective-for-covid19-st-emlyns/.
  4. Simon Carley, “The RECOVERY platform trial: No benefit to Hydroxychloroquine in Covid-19. St Emlyn’s,” in St.Emlyn’s, June 6, 2020, https://www.stemlynsblog.org/the-recovery-platform-trial-no-benefit-to-hydroxychloroquine-in-covid-19-st-emlyns/.
  5. Simon Carley, “Dexamethasone, COVID-19 and the RECOVERY trial. St Emlyn’s,” in St.Emlyn’s, June 28, 2020, https://www.stemlynsblog.org/dexamethasone-covid-19-and-the-recovery-trial-st-emlyns/.
  6. Simon Carley, “JC: Lopinavir/Ritonavir in the treatment of COVID-19,” in St.Emlyn’s, December 23, 2020, https://www.stemlynsblog.org/jc-lopinavir-ritonavir-in-the-treatment-of-covid-19/.
  7. Simon Carley, “JC: Convalescent plasma in COVID 19 patients.,” in St.Emlyn’s, November 21, 2020, https://www.stemlynsblog.org/jc-convalescent-plasma-in-covid-19-patients/.
  8. Simon Carley, “The RECOVERY platform trial: No benefit to Hydroxychloroquine in Covid-19. St Emlyn’s,” in St.Emlyn’s, June 6, 2020, https://www.stemlynsblog.org/the-recovery-platform-trial-no-benefit-to-hydroxychloroquine-in-covid-19-st-emlyns/.


Cite this article as: Simon Carley, "JC: Aspirin is not effective for hospitalised COVID19 patients. St Emlyn’s," in St.Emlyn's, June 8, 2021, https://www.stemlynsblog.org/jc-aspirin-does-not-work-in-hospitalised-covid19-patients-st-emlyns/.

Posted by Simon Carley

Simon Carley MB ChB, PGDip, DipIMC (RCS Ed), FRCS (Ed)(1998), FHEA, FAcadMed, FRCEM, MPhil, MD, PhD is Creator, Webmaster, owner and Editor in Chief of the St Emlyn’s blog and podcast. He is visiting Professor at Manchester Metropolitan University and a Consultant in adult and paediatric Emergency Medicine at Manchester Foundation Trust. He is co-founder of BestBets, St.Emlyns and the MSc in emergency medicine at Manchester Metropolitan University. He is an Education Associate with the General Medical Council and is an Associate Editor for the Emergency Medicine Journal. His research interests include diagnostics, MedEd, Major incidents & Evidence based Emergency Medicine. He is verified on twitter as @EMManchester

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