Efficacy and safety of antiviral treatments for symptomatic COVID-19 outpatients: Systematic review and network meta-analysis.

BACKGROUND: Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death. OBJECTIVES: To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data. STUDY DESIGN: This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated. RESULTS: Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects. CONCLUSIONS: This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors.

Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis.

BACKGROUND: Therapeutic options for intermediate- or high-risk pulmonary embolism (PE) include anticoagulation, systemic thrombolysis and catheter-directed thrombolysis (CDT); however, the role of CDT remains controversial. We sought to compare the efficacy and safety of CDT with other therapeutic options using network meta-analysis. METHODS: We searched PubMed (MEDLINE), Embase, ClinicalTrials.gov and Cochrane Library from inception to Oct. 18, 2022. We included randomized controlled trials and observational studies that compared therapeutic options for PE, including anticoagulation, systemic thrombolysis and CDT among patients with intermediate- or high-risk PE. The efficacy outcome was in-hospital death. Safety outcomes included major bleeding, intracerebral hemorrhage and minor bleeding. RESULTS: We included data from 44 studies, representing 20 006 patients. Compared with systemic thrombolysis, CDT was associated with a decreased risk of death (odd ratio [OR] 0.43, 95% confidence interval [CI] 0.32-0.57), intracerebral hemorrhage (OR 0.44, 95% CI 0.29-0.64), major bleeding (OR 0.61, 95% CI 0.53-0.70) and blood transfusion (OR 0.46, 95% CI 0.28-0.77). However, no difference in minor bleeding was observed between the 2 therapeutic options (OR 1.11, 95% CI 0.66-1.87). Compared with anticoagulation, CDT was also associated with decreased risk of death (OR 0.36, 95% CI 0.25-0.52), with no increased risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63-2.79) or major bleeding (OR 1.24, 95% CI 0.88-1.75). INTERPRETATION: With moderate certainty of evidence, the risk of death and major bleeding complications was lower with CDT than with systemic thrombolysis. Compared with anticoagulation, CDT was associated with a probable lower risk of death and a similar risk of intracerebral hemorrhage, with moderate certainty of evidence. Although these findings are largely based on observational data, CDT may be considered as a first-line therapy in patients with intermediate- or high-risk PE. PROTOCOL REGISTRATION: PROSPERO - CRD42020182163.

Efficacy and safety outcomes of long-term anti-thrombotic treatment of chronic coronary artery disease: A systematic review and network meta-analysis.

Background: Clopidogrel, prasugrel, ticagrelor, and low-dose rivaroxaban are all optional strategies in conjunction with aspirin for long-term treatment of chronic coronary artery disease. The aim of this research was to assess the efficacy and safety of long-term anti-thrombotic treatment of chronic coronary heart disease. Methods: PubMed (MEDLINE), Embase, Clinical Trials Registry ClinicalTrials.gov, and The Cochrane Library were searched through November 2021, to identify randomized controlled trials that compared long term anti-thrombotic therapy for coronary heart disease. Data were extracted to assess eligibility by two independent reviewers. Random-effects meta-analysis was used to pool results. Results: Eleven randomized controlled trials were included (88,462 patients). In a network meta-analysis, the rivaroxaban compared to the clopidogrel regimen showed lower relative risks (RRs) for death of any cause (0.71; 95% confidence interval [CI], 0.52-0.96), major adverse cardiac events (MACE) (0.73; 95% CI, 0.57-0.93), and cerebrovascular events (0.48; 95% CI, 0.30-0.78). The RR of cerebrovascular events was also lower for the rivaroxaban compared to the ticagrelor 60 mg regimen (0.72; 95% CI, 0.52-0.99). For the prasugrel regimen, the RRs were lower of myocardial infarction incidence versus all extended strategies: clopidogrel plus aspirin (0.76; 95% CI, 0.58-0.99), rivaroxaban (0.60; 95% CI, 0.38-0.93), ticagrelor 60 mg (0.61; 95% CI, 0.42-0.89), and ticagrelor 90 mg (0.63; 95% CI, 0.41-0.97). None of the dual strategies were associated with differences in major bleeding compared to the prasugrel regimen. Conclusions and relevance: The rivaroxaban regimen appeared to be the preferred long-term anti-thrombotic regimen in preventing all-cause mortality. Our available results tend to support the efficacy of extended anti-thrombotic therapy consisting of prasugrel in lowering MI incidence compared to the other strategies, without increased risk of bleeding. However, additional large-scale direct clinical trials are needed to further determine the adequate long-term anti-thrombotic regimens for treating chronic coronary syndrome. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186583, identifier CRD42020186583.