Meta-Analysis Addressing the Efficacy and Safety of Antiplatelet Agents in Patients With COVID-19.

The COVID-19 pandemic has led to more than 6 million deaths worldwide since its initial outbreak in China in December 2019. Patients with COVID-19, especially those being critically ill and admitted to the hospital, feature an increased risk for thrombotic complications involving both the arterial and venous systems.1, 2, 3 Therefore, it has been speculated whether antithrombotic treatment could lead to improved outcomes in patients with COVID-19. A former meta-analysis of observational studies demonstrated a nonsignificant effect of aspirin on COVID-19–related death, whereas other meta-analyses had contradictory results. Therefore, it remains unknown whether antiplatelet agents, in general, could improve the clinical status and disease course of patients with COVID-19. Because we recently welcomed the results of randomized controlled trials, we sought to determine the efficacy and safety of antiplatelet agents in COVID-19, evaluating the most surrogate outcomes.

We searched PubMed and Cochrane Library databases for randomized controlled trials enrolling adult patients with COVID-19 assigned either to an antiplatelet agent (any of them) plus standard of care compared with standard of care alone. We excluded observational studies and studies performed in the pediatric population if any.

We set as the primary efficacy outcome the effect of antiplatelet agents compared with control on the risk for COVID-19 death. We assessed the following secondary outcomes: major thrombosis and major bleeding.

Two independent reviewers (DP and CP) extracted the data of interest from the eligible trials using a pilot-tested data extraction form.

As we assessed only dichotomous variables, differences were calculated with the use of risk ratio (RR), with 95% confidence interval (CI), after implementation of the Mantel-Haenszel random effects formula. Statistical heterogeneity in studies was assessed using I2 statistics. All analyses were performed at the 0.05 significance level and were undertaken with Review Manager (RevMan) Version 5.3 Software (The Cochrane Collaboration, 2020).

We finally pooled data from 3 trials in a total of 15,782 enrolled participants with COVID-19.6, 7, 8 Regarding the primary efficacy outcome, we demonstrated that antiplatelet agents compared with control resulted in a nonsignificant decrease in the risk for death (RR = 0.97, 95% CI 0.90 to 1.04, I2 = 0%, p = 0.38), as shown in Figure 1 . Concerning the risk for major thrombosis, antiplatelet agents resulted in a marginally nonsignificant decrease in the corresponding risk compared with control (RR = 0.88, 95% CI 0.77 to 1.02, I2 = 0%, p = 0.08), as shown in Figure 2 . However, a significant increase in the risk for major bleeding with antiplatelet agents versus control by 58% was documented (RR = 1.58, 95% CI 1.19 to 2.10, I2 = 0%, p = 0.002), as shown in Figure 3 .

Figure 1

Effect of antiplatelet agents compared with control on the risk for COVID-19 death.

Figure 2

Effect of antiplatelet agents compared with control on the risk for major thrombosis in patients with COVID-19.

Figure 3

Effect of antiplatelet agents compared with control on the risk for major bleeding in patients with COVID-19.

Therefore, we can conclude that the use of antiplatelet agents in patients with COVID-19, either in the inpatient or the outpatient setting, does not confer a significant effect on the risk of COVID-19 related death. However, it is associated with a significantly increased risk of major bleeding.

Disclosures

The authors have no conflicts of interest to declare.