Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis

Abstract

Background Previous studies demonstrate a reduced risk of thrombosis and mortality with anticoagulant treatment in patients with COVID-19 than in those without anticoagulation treatment. However, an open question regarding the efficacy and safety of therapeutic anticoagulation (T-AC) versus a lower dose, prophylaxis anticoagulation (P-AC) in COVID-19 patients is still controversial. Methods We systematically reviewed currently available randomized clinical trials (RCTs) and observational studies (OBs) from January 8, 2019, to January 8, 2022, and compared prophylactic and therapeutic anticoagulant treatment in COVID-19 patients. The primary outcomes were risk of mortality, major bleeding, and the secondary outcomes included venous and arterial thromboembolism. Subgroup analysis was also performed between critically ill and non-critically ill patients with COVID-19 and between patients with higher and lower levels of D-dimer. Sensitivity analysis was performed to decrease the bias and the impact of population heterogeneity. Results We identified 11 RCTs and 17 OBs fulfilling our inclusion criteria. In the RCTs analyses, there was no statistically significant difference in the relative risk of mortality between COVID-19 patients with T-AC treatment and those treated with P-AC (RR 0.95, 95% CI, 0.78–1.15, P = 0.60). Similar results were also found in the OBs analyses (RR 1.21, 95% CI, 0.98–1.49, P = 0.08). The pooling meta-analysis using a random-effects model combined with effect sizes showed that in the RCTs and OBs analyses, patients with COVID-19 who received T-AC treatment had a significantly higher relative risk of the major bleeding event than those with P-AC treatment in COVID-19 patients (RCTs: RR 1.76, 95% CI, 1.19–2.62, P = 0.005; OBs: RR 2.39, 95% CI, 1.56–3.68, P < 0.0001). Compared with P-AC treatment in COVID-19 patients, patients with T-AC treatment significantly reduced the incidence of venous thromboembolism (RR 0.51, 95% CI, 0.39–0.67, P<0.00001), but it is not associated with arterial thrombosis events (RR 0.97, 95% CI, 0.66–1.42, P = 0.87). The subgroup analysis of OBs shows that the mortality risk significantly reduces in critically ill COVID-19 patients treated with T-AC compared with those with P-AC treatment (RR 0.58, 95% CI, 0.39–0.86, P = 0.007), while the mortality risk significantly increases in non-critically ill COVID-19 patients treated with T-AC (RR 1.56, 95% CI, 1.34–1.80, P < 0.00001). In addition, T-AC treatment does not reduce the risk of mortality in COVID-19 patients with high d-dimer levels in RCTs. Finally, the overall sensitivity analysis after excluding two RCTs studies remains consistent with the previous results. Conclusions In our integrated analysis of included RCTs and OBs, there is no significant difference between the mortality of T-AC and P-AC treatment in unselected patients with COVID-19. T-AC treatment in COVID-19 patients significantly reduced the incidence of venous thromboembolism but showed a higher risk of bleeding than those with P-AC treatment. In addition, P-AC treatment was superior to T-AC treatment in non-critically ill COVID-19 patients, the evidence supporting the necessity for T-AC treatment in critically ill COVID-19 patients came only from OBs. Trial registration Protocol registration: The protocol was registered at PROSPERO (CRD42021293294). Graphical abstract

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis

“…Our analysis including recently published RCTs [ 25 , 53 , 54 , 56 ] confirmed the main finding of previous meta-analyses [ 73 , 74 , 75 , 76 , 77 , 78 , 79 ] and endorsed the current guidelines ( Table S3 in Supplementary Material ) [ 80 , 81 , 82 , 83 ]. On the basis of our results, we cannot advocate for the routine use of therapeutic dose thromboprophylaxis in all COVID-19 patients either.…”

Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials

“…Since the efficacy of antiviral drugs and corticosteroids in treating COVID-19 is not well-proven [ 28 ], studies determined the effectiveness of more available and cheaper medications such as statins [ 29 ], antiplatelets [ 30 ], and anticoagulants [ 31 ] in decreasing post-infection complications. The rationale behind choosing anti-dyslipidemic agents ( e.g., statins) in COVID-19 patients is the role of dyslipidemia and cardiovascular complications in the prognosis of COVID-19.…”