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Antiplatelet therapy for patients with COVID-19: Systematic review and meta-analysis of observational studies and
Xiaolong Zong1,2, Xiao Wang3, Yaru Liu3
1Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China.
Insights
Early observational studies suggested antiplatelet agents reduce mortality in COVID-19 patients. However, recent randomized controlled trials (RCTs) did not confirm these benefits, indicating antiplatelet therapy is not supported for standard COVID-19 care.
Area of Science:
- Internal Medicine
- Infectious Diseases
- Pharmacology
Background:
- COVID-19 is characterized by hyperinflammation and coagulopathy, increasing illness severity.
- Antiplatelet agents, with antithrombotic and anti-inflammatory properties, were explored as potential COVID-19 treatments.
- A systematic review and meta-analysis synthesized evidence from observational studies and RCTs on antiplatelet therapy in COVID-19.
Approach:
- Searched PubMed, Embase, and CENTRAL for studies up to November 2021, with clinical trial follow-up to March 2022.
- Included observational studies and randomized controlled trials (RCTs) assessing antiplatelet therapy in adult COVID-19 patients.
- Pooled data from 23 observational studies (87,824 patients) using a random-effects model and narratively synthesized four RCTs.
Key Points:
- Observational studies (n=87,824) indicated antiplatelet treatment was associated with a lower risk of mortality (OR 0.72, 95% CI 0.61-0.85).
- Randomized controlled trials (RCTs) provided conflicting evidence.
- The RCT evidence did not support the addition of antiplatelet therapy to standard care for COVID-19 patients.
Conclusions:
- Despite a compelling rationale and supportive observational data, RCTs failed to confirm the efficacy of antiplatelet agents in COVID-19.
- Inconsistencies between study types may be due to various factors requiring further investigation.
- Future research is needed to clarify the role, if any, of antiplatelet therapy in managing COVID-19.
Background:
Hyperinflammation and coagulopathy are hallmarks of COVID-19 and synergistically contribute to illness progression. Antiplatelet agents have been proposed as candidate drugs for COVID-19 treatment on the basis of their antithrombotic and anti-inflammatory properties. A systematic review and meta-analysis that included early observational studies and recent randomized controlled trials (RCTs) was performed to summarize and compare evidence on this issue.
Methods:
PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify studies published up to Nov 7, 2021, and the results of registered clinical trials were followed up to Mar 30, 2022. We included RCTs and observational studies assessing the effect of antiplatelet therapy in adult patients with COVID-19. Data on baseline patient characteristics, interventions, controls, and outcomes were extracted by two independent reviewers. The primary outcome was mortality. Data were pooled using a random-effects model.
Results:
Twenty-seven studies were included, of which 23 observational studies were pooled in a meta-analysis, and the remaining four RCTs (ACTIV-4B, RECOVERY, ACTIV-4a, and REMAP-CAP) were narratively synthesized. Based on 23 observational studies of 87,824 COVID-19 patients, antiplatelet treatment favors a lower risk of mortality [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.61-0.85; I 2 = 87.0%, P < 0.01]. The narrative synthesis of RCTs showed conflicting evidence, which did not support adding antiplatelet therapy to the standard care, regardless of the baseline illness severity and concomitant anticoagulation intensity.
Conclusion:
While the rationale for using antiplatelet treatment in COVID-19 patients is compelling and was supported by the combined result of early observational studies, evidence from RCTs did not confirm this approach. Several factors that could explain this inconsistency were highlighted alongside perspectives on future research directions.
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