Source: Health Community - Clinical Frontline
Since March, the mainland's epidemic prevention and control seems to have entered a new stage, even if various measures are taken, the number of local infection cases in the country is still increasing at a rate of thousands of cases per day, and the recent epidemic in Shanghai has attracted much attention - the menacing Olmikron mutation strain has pushed the new crown virus pandemic to a new peak. Although the data shows that the pathogenicity of Omi kerong has declined, considering the huge number of infected people, even if the mortality rate is very low, the final death toll is certainly staggering, and we still need to explore some medical measures to further reduce the occurrence of COVID-19-related deaths.
Shanghai epidemic 丨 Image source Weibo
The new coronavirus causes blood clots, and aspirin may be treatable
After the new crown virus infects the human body, in addition to damaging the respiratory system, it is often accompanied by other complications. Autopsies of patients infected with COVID-19 reveal fibrin thrombosis and extensive extracellular fibrin deposits in swollen fine blood vessels and capillaries, suggesting coagulation disorders in patients with COVID-19 [1].
One study assessed the incidence of venous and arterial thrombosis in all hospitalized COVID-19 patients in 4 large hospitals in New York, including a total of 3334 patients with an average age of 64 years, with 533 patients (16.0%) developing thrombotic events, including 207 (6.2%) with venous embolism and 365 (11.1%) with arterial embolism.
The all-cause mortality rate was 24.5 percent in all hospitalized patients, and the occurrence of thrombotic events was associated with higher mortality, with a mortality rate of 43.2 percent in people with thrombotic events and 21 percent in patients without thrombosis [2].
Based on the above data, the treatment and prevention of thrombosis may help treat patients with COVID-19 and even reduce mortality in patients with COVID-19. Platelet activation is one of the causes of thrombosis, and aspirin is a widely studied antiplatelet therapy drug, low doses of aspirin can irreversibly inhibit cyclooxygenase-1, thereby inhibiting the production of thromboxane.
The use of aspirin in the clinical treatment of COVID-19 may have potential benefits for patients, but the specific benefits depend on the validation of clinical trials, based on which researchers have conducted a series of clinical trials on aspirin for patients with new coronary pneumonia.
ACTIV-4B: Aspirin does not alleviate the cardiopulmonary adverse events caused by COVID-19
ACTIV-4B is a randomized, double-blind, placebo-controlled trial [3] to assess whether the addition of antithrombotic therapy to symptomatic but stable COVID-19 outpatients can reduce major cardiopulmonary events compared with placebo. The 657 patients were randomly divided into four groups on a 1:1:1:1 ratio, given aspirin (n=164), a prophylactic dose of apixaban (an anticoagulant for venous thromboembolism and atrial fibrillation stroke, n = 165), a therapeutic dose of apixaban (n=164) or a placebo (n=64) for 45 days. The primary endpoints of the study were all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary disease.
DOI:10.1001/jama.2021.17272 丨 Image source JAMA
During the study period, 22 participants (3.3%) were admitted to hospital for COVID-19 before initiation of treatment, and of the 558 patients who started treatment, the primary endpoint was achieved in 1 patient in the aspirin (0.7%) group, 1 patient in the apixaban (0.7%) group in the prophylactic dose, 2 patients in the apixaban (1.4%) group with therapeutic dose, and 1 patient in the placebo (0.7%) group. Compared with the placebo group, the risk differences in the aspirin group, the apixaban group at the prophylactic dose, and the apixaban group at the therapeutic dose were 2.0%, 4.5%, and 6.9%, respectively.
The results of this study showed that in clinically stable symptomatic COVID-19 patients, aspirin or apixaban did not improve the incidence of cardiovascular or pulmonary events.
RECOVERY: Aspirin does not reduce 28-day mortality in COVID-19 hospitalizations
The RECOVERY study[4] was a randomized, controlled, open-label, platform trial conducted in 177 hospitals in the UK, 2 in Indonesia, and 2 in Nepal to assess the efficacy and safety of aspirin in hospitalized patients with COVID-19. Eligible participants were randomly assigned to the regular care + 150 mg aspirin group once a day in a 1:1 ratio and to the routine care group only.
Between 1 November 2020 and 21 March 2021, 14,892 patients were eligible for trial inclusion, of which 7,351 received aspirin and 7,541 individually received routine treatment. Within 28 days, there were 1222 deaths in the aspirin-treated group, with a mortality rate of 17%, compared with 1299 deaths in the conventional treatment group, also with a mortality rate of 17%. However, patients in the aspirin group had a slightly shorter hospital stay, with a median of 8 days compared to 9 days in the control group, with a higher rate of 75% of patients discharged within 28 days and 74% of the control group. The use of aspirin, while beneficial for a reduction in thrombotic events (4.6% vs 5.3%), increased major bleeding events (1.6% vs 1.0%).
Effect of aspirin on 28-day mortality in hospitalized COVID-19 丨 Image source RECOVERY
The RESULTS suggest that low-dose aspirin does not significantly reduce the risk of death within 28 days of hospitalization due to COVID-19, but it can reduce the length of hospital stay for patients slightly, increasing the probability that patients will be discharged alive within 28 days.
REMAP-CAP: Aspirin improves survival within 90 days in severe COVID-19 patients
A new study published in JAMA evaluated whether antiplatelet therapy, including aspirin, could improve outcomes for patients with severe COVID-19 [5], and between 30 October 2020 and 23 June 2021, 1557 patients with severe illness from 105 trial sites in 8 countries were randomly divided into aspirin group (n=565) and P2Y12 inhibitor group (an antiplatelet drug, n=). 455) and a control group without antiplatelet therapy (n=529). The primary study endpoint was 21 days, without the need for organ support. The results showed that the median number of days without tracheal support in both the antiplatelet group and the control group was 7 days, which means that antiplatelet therapy was less likely to improve the number of organless support days in severe COVID-19 patients within 21 days. However, antiplatelet therapy can improve the survival rate of patients from hospital discharge, which is 71.5% in the antiplatelet group and 67.9% in the control group, and according to the data in this article, the probability of antiplatelet therapy improving the 90-day survival rate of severe patients is 99.7%.
All-cause mortality rate in each group within 90 days 丨 Image source JAMA
Considering the huge global population of patients with new crown infection, and antiplatelet drugs such as aspirin are inexpensive, easy to obtain and use, aspirin still has a certain use value in patients with severe coronavirus disease.
Author: Yin Qilei
Source: Clinical Frontline
Resources
1.Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood 2020;136:489-500.
2.Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. Jama 2020;324:799-801.
3.Connors JM, Brooks MM, Sciurba FC, et al. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. Jama 2021;326:1703-12.
4.Liuzzo G, Patrono C. Can low-dose aspirin help the RECOVERY of patients hospitalized with COVID-19? European Heart Journal 2022;43:714-5.
5.Investigators R-CWCftR-C. Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial. Jama 2022.