Aspirin does not cut death risk in hospitalized COVID-19 patients

Adding aspirin to usual care did not lead to a reduced mortality rate in patients hospitalized with COVID-19, according to a study by the RECOVERY* Collaborative Group.

“[A]llocation to aspirin was not associated with reductions in mortality or, among patients not on invasive mechanical ventilation at baseline, the risk of progressing to the composite endpoint of invasive mechanical ventilation or death,” the researchers noted.

“Allocation to aspirin was, however, associated with a small increase in the rate of being discharged from hospital alive within 28 days,” they said.

The multicentre study was conducted at 167 hospitals in the UK and two hospitals each in Indonesia and Nepal and involved 14,892 adults (mean age 59.2 years) hospitalized with clinically suspected or laboratory-confirmed SARS-CoV-2 infection (median 9 days since symptom onset). They were randomized 1:1 to receive either usual standard of care (SoC) alone (n=7,541) or in addition to aspirin (150 mg QD; n=7,351) until hospital discharge.

Seventy-seven percent of patients were aged <70 years. Thirty-four percent of patients were receiving thromboprophylaxis with higher-dose low molecular weight heparin (LMWH) at baseline, while 60 percent were receiving standard-dose LMWH.

Mortality rate at 28 days was similar between patients assigned to SoC plus aspirin and SoC alone (17 percent in each group; rate ratio [RR], 0.96, 95 percent confidence interval [CI], 0.89–1.04; p=0.35). [Lancet 2021;doi:10.1016/S0140-6736(21)01825-0]

The results were consistent when limited to the 14,467 patients with positive SARS-CoV-2 test results (RR, 0.96).

Median duration of hospitalization** was 1 day shorter in the aspirin compared with the SoC alone group (8 vs 9 days). More patients on aspirin than SoC alone were discharged alive within 28 days (75 percent vs 74 percent; RR, 1.06, 95 percent CI, 1.02–1.10; p=0.0062).

The composite of invasive mechanical ventilation or death among patients not receiving invasive mechanical ventilation at baseline was similar between the aspirin and SoC alone groups (21 percent vs 22 percent; risk ratio, 0.96, 95 percent CI, 0.90–1.03; p=0.23).

Subgroup analyses showed that the effect of allocation to aspirin on time to discharge alive and the composite of invasive mechanical ventilation or death was consistent regardless of age, sex, ethnicity, pre-randomization symptom duration, respiratory support at baseline, and use of corticosteroids. Exploratory analysis showed that the use of LMWH at baseline did not appear to affect the results.

Use of ventilation did not differ between the aspirin and SoC alone groups (23 percent vs 24 percent; RR, 0.96; p=0.30), nor did successful cessation of invasive mechanical ventilation (38 percent vs 36 percent; RR, 1.08; p=0.54) or receipt of renal replacement therapy (4 percent in each group; RR, 0.99; p=0.93).

Incidence of thrombotic events was lower in the aspirin vs SoC alone group (4.6 percent vs 5.3 percent), while incidence of major bleeding was higher with aspirin (1.6 percent vs 1.0 percent). Incidence of new cardiac arrhythmia was comparable between groups. Eighteen serious adverse events (all haemorrhagic) deemed related to aspirin were reported.

“[F]or every 1,000 patients treated with aspirin, approximately six more patients would have a major bleeding event and approximately six fewer patients would have a thromboembolic event,” the researchers said.

“Thrombosis is a key feature of severe COVID-19 ... the pathogenesis of thromboembolism in COVID-19 is likely to be multifactorial,” they continued, highlighting that prior research has suggested a potential benefit of antithrombotic therapy in certain patients with COVID-19. [N Engl J Med 2021;385:790-802]

“[Our findings] do not support the addition of aspirin to standard thromboprophylaxis or therapeutic anticoagulation in patients hospitalized with COVID-19,” the researchers said. This lack of benefit could be attributed to no additional benefit derived from antiplatelets in addition to LMWH or that “non-platelet pathways” may have greater bearing on clinical outcomes. Timing of treatment initiation may also play a role, they added. However, research is ongoing to assess the effect of aspirin in patients with COVID-19 who are not hospitalized.