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Step-Based Dosing of Anticoagulants in COVID-19 Treatment
Minh-Hoang Tran1, Hoang Hai Nguyen2, Quang Trung Nguyen2
1Therapeutics, NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, VNM.
Insights
Step-based anticoagulant dosing in COVID-19 patients showed that increasing doses (prophylactic-to-therapeutic) reduced adverse events. However, therapeutic anticoagulation alone increased bleeding risk, highlighting the importance of tailored anticoagulant strategies.
Area of Science:
- Internal Medicine
- Pharmacology
- Critical Care Medicine
Background:
- Step-based anticoagulant dosing is common for COVID-19 but lacks comprehensive effectiveness and safety data.
- Previous studies have not fully evaluated step-based anticoagulant strategies against standard prophylactic dosing.
Purpose of the Study:
- To compare the clinical outcomes of step-based anticoagulant dosing versus standard prophylactic dosing in hospitalized COVID-19 patients.
- To assess the effectiveness and safety of different anticoagulant dosing strategies in COVID-19.
Main Methods:
- Retrospective cohort study of adults hospitalized with moderate-to-severe COVID-19.
- Categorized anticoagulant regimens: prophylactic (PrA), prophylactic-to-therapeutic (Pr-to-ThA), therapeutic (ThA), and therapeutic-to-prophylactic (Th-to-PrA).
- Primary outcomes included composite of mortality, ICU admission, stroke, VTE (effectiveness) and bleeding events (safety).
Main Results:
- The prophylactic-to-therapeutic (Pr-to-ThA) group showed a significantly lower risk of adverse effectiveness outcomes compared to standard prophylactic anticoagulation (PrA) (aOR 0.64).
- Therapeutic anticoagulation (ThA) and therapeutic-to-prophylactic (Th-to-PrA) dosing were associated with increased risks of bleeding events (aORs 3.05 and 3.00, respectively).
- No significant increase in bleeding risk was observed for the Pr-to-ThA group compared to PrA.
Conclusions:
- Step-based anticoagulant therapy, specifically increasing from prophylactic to therapeutic doses, is associated with reduced composite adverse outcomes in COVID-19 patients.
- Standard therapeutic anticoagulation (ThA) dosing increases bleeding risk, primarily minor and clinically relevant non-major bleeding.
- Dose-escalation strategies may offer a favorable balance of efficacy and safety in hospitalized COVID-19 patients, warranting further investigation.
Background:
Step-based dosing of anticoagulants has been widely implemented for the treatment of coronavirus disease 2019 (COVID-19), but no studies have comprehensively evaluated the effectiveness and safety of this approach. We aimed to investigate whether step-based dosing of anticoagulants was associated with clinical outcomes in patients with COVID-19 compared with standard prophylactic dosing.
Method:
We conducted a retrospective cohort study on adults hospitalized with moderate-to-severe COVID-19. The exposure was step-based dosing of anticoagulants, including prophylactic anticoagulants (PrA), prophylactic-switching-to-therapeutic anticoagulants (Pr-to-ThA), therapeutic anticoagulants (ThA), and therapeutic-switching-to-prophylactic anticoagulants (Th-to-PrA). The primary effectiveness outcome was a composite of all-cause mortality, admission to an intensive care unit (ICU admission), stroke, and venous thromboembolism (VTE). The primary safety outcome was a composite of major and minor/clinically relevant non-major (CRNM) bleeding.
Results:
Among 1,081 records for analysis (mean age 59.9, 49.9% being female), during a median follow-up of 15 days, the primary effectiveness outcome occurred in 333 patients (33.5% in the PrA group, 24.6% in the Pr-to-ThA group, 23.7% in the Th-to-PrA group, and 38.0% in the ThA group). Compared with the PrA group, patients receiving Pr-to-ThA had a lower risk of the primary effectiveness outcome (adjusted odds ratio (OR) 0.64, 95% CI: 0.45 to 0.90, Dunnett-adjusted p = 0.01), while those in the Th-to-PrA and ThA were more likely to experience the primary safety outcome (Th-to-PrA, aOR = 3.00, 95% CI: 1.53 to 5.89; ThA, aOR = 3.05, 95% CI: 1.61 to 5.79).
Conclusion:
In adults hospitalized with moderate-to-severe COVID-19, compared with standard PrA, the step-based dose-increasing therapy was associated with a lower composite risk of all-cause mortality, ICU admission, stroke, or VTE without evidence of a higher risk of bleeding. ThA dosing was associated with an increase in the bleeding risk, primarily minor and CRNM bleeding.
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