Aspirin & COVID-19: Does it Decrease the Severity of Illness?

Addendum: As data changes, perspectives should change, too. This post on aspirin and COVID was initially posted on 10/25/20. Since then more robust data has been published. I have left my perspective up on this page for the sake of transparency. The original post starts now. Let’s answer the first question these academic elites will ask the moment we even think about providing aspirin empirically to our COVID patients. Is there a prospective, randomized-controlled trial to show that aspirin decreases the severity of COVID? The answer to that question is a resounding no. So those people who are seeking to bash this post and paper can go ahead and do so. But at the same time, a search for “aspirin, COVID” on will yield zero results. That means no one is seriously prospectively studying this. That also means that if it does actually work, we will never know.

So the question becomes, are we going to be these people who have our heads so far up our backside waiting for an RCT that we will never try something that mechanistically should work and lose patients in this process? The same people who want to keep every everyone indoors, businesses closed indefinitely and say “follow the science” like a religious mantra are the same ones to ignore a paucity of studies that are not involving some monoclonal antibody or drugs that are resurrected from the dead like Remdesivir. That being said, I am not recommending putting aspirin in the drinking water of our COVID patients just yet.

Addendums containing new studies looking at Aspirin in COVID

ADDENDUM on 11/12/21:
check out the citations for links to the RECOVERY trial data that states that aspirin in COVID does not change outcomes and a paper published in October 2021 that says it might help. This back and forth makes me crazy.

ADDENDUM on 11/18/21:
The RECOVERY trial data on Aspirin is finally published in the Lancet. It only took 5 months. I really wonder what took them so long. Either way, chances are that you’re here right now to read that paper for yourself. Here’s the citation:
RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022 Jan 8;399(10320):143-151. doi: 10.1016/S0140-6736(21)01825-0. Epub 2021 Nov 17. PMID: 34800427; PMCID: PMC8598213.
Link to the Article
Link to the FULL FREE PDF

ADDENDUM on 03/22/22: The REMAP-CAP group published their data on the matter.
REMAP-CAP Writing Committee for the REMAP-CAP Investigators. Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA.Published online March 22, 2022. doi:10.1001/jama.2022.2910
Link to Article and FULL FREE PDF

ADDENDUM on 4/20/22: Why some studies can be ignored. Keep scrolling down to see my take here.

Digging into the paper.

This paper was published in Anesthesia & Analgesia on October 21st and is free for you to download in the link below. Do not trust me. Read it for yourself. The authors state some mechanisms and rationales for hypercoagulation in COVID. Any of us who have taken care of COVID patients know quite well of this phenomenon. Many of us are therapeutically anticoagulating these patients based on our best judgement mitigate their disease or hold over the prothrombotic phase until it passes. Do you know what is the evidence to go ahead and do so? I challenge you to look it up.

The authors performed a retrospective study looking at aspirin with the need for mechanical ventilation as the primary objective followed by reducing the risk for ICU admission and in-hospital mortality. They found that people who were either on aspirin in the 7 days prior to hospital admission or provided aspirin in the first 24 hours of admission to the hospital as those with “aspirin use”. I am not going to dive into the statistical jumping jacks the authors did to obtain their numbers. Again, check that out in the article.

Let’s look at some important numbers/facts from this study

  • 412 patients in the study (98 in the ASA arm)
  • 81mg daily was the dose
  • patients on aspirin had more diabetes, hypertension, CAD, etc.
  • non-aspirin users were sicker on admission (more HFNC, NIV, etc.)
  • qSOFA scores were the same in both groups on admission
  • APACHEII scores were higher on ICU admit in the ASA group.
  • the d-dimer and use of therapeutic heparin was the same in both groups

What did they find in COVID patients who received aspirin?

  • Decreased risk of mechanical ventilation (adjusted HR 0.56, 95% CI 0.37-0.85, p=0.007)
  • Decreased risk of ICU admission (adjusted HR 0.57, 95% CI 0.38-0.85, p=0.005)
  • Lower risk of in-hospital mortality (adjusted HR 0.53, 95% CI 0.31-0.90, p=0.02)

Should we be putting aspirin in the water of our COVID patients?

The answer here is no. But I believe that if someone should be on an aspirin anyway, due to the risk factors that would typically require them to be on an aspirin anyway, they why not give it a go? Otherwise, I believe that we should empower patients and discuss the possible risks versus benefits of starting this therapy. You know, like mention to them the increased risk of GI bleeds. People worry quite a bit regarding dexamethasone and GI bleeds to start, then add aspirin to the mix and they will panic even more.

I recommend you check out the limitations to this study. That’s where the authors confess the shortcomings to their paper. For example, 53.1% of the patients in the aspirin arm were on room air. Why in the world were they hospitalized if they were on room air on admission? I digress. We need to look into this some more. Consider it a call to arms for those of you with research/NIH money to invest some time and energy into looking into cheap, safe, and readily available therapies to help save lives in COVID patients.

CLICK HERE for my other posts on COVID-19

Check this out on my podcast/YouTube channel

Addendum on 4/20/22: Why some papers on Aspirin in COVID can be ignored.

When I opened up my email in mid April of 2022, I saw this paper in JAMA titled “Association of early aspirin use with in hospital mortality in patients with moderate COVID-19”. I thought to myself, “hasn’t this issue been put to bed yet”? Well, for the uninitiated, this appears to be a positive study in favor of providing patients with 81 mg of aspirin on the first day of hospitalization. This is where some experience at interpreting the nuance of studies comes to play. Just a friendly reminder that the rationale behind giving patients with COVID-19 aspirin is to reduce cardiovascular as well as pulmonary events. We have all seen patients who develop myocardial infarction and pulmonary emboli secondary to COVID-19. These thrombotic phenomenon could be potentially mitigated by aspirin. Or so we have hoped.

I will commend the authors of the study for their work within the construct of the data accessible to them. This paper is a cohort study where they took the patients from a database. This is not a prospective randomized placebo controlled trial like many would want it to be. I understand the limitations. All these data came from US-based hospitals. In this study, compared to others, they use patients with moderate disease. They kept the definitions simple as patients with mild disease were asymptomatic or symptomatic but not requiring hospitalization, moderate disease where patients requiring hospitalization. Lastly, severe disease were patients who died, needed invasive mechanical ventilation, basil pressures are inotropes, or ECMO.

They collected data from January 2020 up to September 2020. In other words it encompassed the first two strains of the SARS-CoV-2 virus that we saw in the states. Delta did not come to visit us until mid-2021. I feel that the data should be applicable for subsequent variants, though. But this is my opinion. I am not going to review their statistical analysis as this is beyond the scope of a podcast intended for you to not fall asleep listening to. All in all, they assessed almost 8,000,000 patients and almost 200,000 of them were hospitalized. I always dedicate a few minutes when I read journal articles to look at the baseline demographics of the patients. In this case it seems as if it’s appropriate as the median age or patients in their 60s. Most of them had comorbidities as one would expect from patients who are hospitalized with moderate COVID-19. The interesting component, however, is that the majority of patients were not started on dexamethasone on the first day. This is where we have to remember and take into account the time period in which they collected data.

So let’s start diving into the outcomes of the study. First, the primary outcome was in hospital mortality. Yes one just looks at the P value which is <0.001, then you would think that this is a positive study and aspirin needs to be put into the drinking water. Yes, it is statistically significant to benefit when it comes to in-hospital mortality as the mortality in patients who took aspirin was 10.2% versus 11.8% in the patients who did not take aspirin. There’s more to this though. If you plug in those numbers into a number needed to treat calculator you would see that you would have to treat 62.5 patients with aspirin to have one life saved. This is not a very efficacious therapy. Usually, we’d like to see a number needed to treat that is far lower than 63. Usually in the single digits makes us happy. I know what you are thinking. I thought the same thing. If it is just a baby aspirin to 63 people in order to save a life, should we just do it? Perhaps earlier in the pandemic this might have been an appropriate thought pattern. The data at this moment suggests that we should have patients with moderate COVID-19 on full dose anticoagulation with, for example, heparin or enoxaparin.

Obviously, one would be worried about bleeding complications by giving patients aspirin across-the-board. They did not find a statistically significant difference in G.I. bleeds, cerebral hemorrhage, blood transfusions, nor composite of hemorrhagic complications. But again, if we were to start giving patients aspirin in addition to their full dose anticoagulation then we may be seeing more complications than what these data have provided.

When it came to the secondary outcomes, they found that there was a benefit in the percentage of patients who developed a pulmonary embolism. Once again, this was statistically significant with a P value of 0.004. Now, you take the incidence of pulmonary emboli in patients who were taking aspirin which was 1.0% compared to those who are not taking aspirin which was 1.4%. You plug these numbers into a number needed to treat calculator and it it means that you would have to treat 250 patients for the secondary outcome of decreasing the risk of pulmonary emboli. There was no difference in DVTs amongst patients who received aspirin and those who didn’t.

To wrap up my post on this particular study, I do not think that we should be placing aspirin in the drinking water. Other prospective studies have not shown a benefit. And we have to remember that these patients were not receiving the therapy that is now standard of care for this patient population. The therapy, of course is full dose anticoagulation. Perhaps aspirin could be provided to the patients who cannot tolerate full-dose anticoagulation but that is not a recommendation. As always, I recommend that you read this article for yourself and do not trust me. It’s free for you to download in the citations below.

Citation for Aspirin and COVID

Chow JH, Khanna AK, Kethireddy S, Yamane D, Levine A, Jackson AM, McCurdy MT, Tabatabai A, Kumar G, Park P, Benjenk I, Menaker J, Ahmed N, Glidewell E, Presutto E, Cain S, Haridasa N, Field W, Fowler JG, Trinh D, Johnson KN, Kaur A, Lee A, Sebastian K, Ulrich A, Peña S, Carpenter R, Sudhakar S, Uppal P, Fedeles BT, Sachs A, Dahbour L, Teeter W, Tanaka K, Galvagno SM, Herr DL, Scalea TM, Mazzeffi MA. Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19. Anesth Analg. 2020 Oct 21. doi: 10.1213/ANE.0000000000005292. Epub ahead of print. PMID: 33093359.
Link to Article

Group  RC, Horby  PW, Pessoa-Amorim  G, Staplin  N,  et al; RECOVERY Collaborative Group.  Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.   medRxiv. Preprint posted online June 8, 2021. doi:10.1101/2021.06.08.21258132
Link to Article

Santoro F, Nuñez-Gil IJ, Vitale E, Viana-Llamas MC, Reche-Martinez B, Romero-Pareja R, Feltez Guzman G, Fernandez Rozas I, Uribarri A, Becerra-Muñoz VM, Alfonso-Rodriguez E, Garcia-Aguado M, Huang J, Ortega-Armas ME, Garcia Prieto JF, Corral Rubio EM, Ugo F, Bianco M, Mulet A, Raposeiras-Roubin S, Jativa Mendez JL, Espejo Paeres C, Albarrán AR, Marín F, Guerra F, Akin I, Cortese B, Ramakrishna H, Macaya C, Fernandez-Ortiz A, Brunetti ND. Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry. Heart. 2021 Oct 5:heartjnl-2021-319552. doi: 10.1136/heartjnl-2021-319552. Epub ahead of print. PMID: 34611045; PMCID: PMC8494537.
Link to Article

Chow JH, Rahnavard A, Gomberg-Maitland M, Chatterjee R, Patodi P, Yamane DP, Levine AR, Davison D, Hawkins K, Jackson AM, Quintana MT, Lankford AS, Keneally RJ, Al-Mashat M, Fisher D, Williams J, Berger JS, Mazzeffi MA, Crandall KA; N3C Consortium and ANCHOR Investigators. Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19. JAMA Netw Open. 2022 Mar 1;5(3):e223890. doi: 10.1001/jamanetworkopen.2022.3890. PMID: 35323950; PMCID: PMC8948531.
Link to Article and FULL FREE PDF


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