Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital‐admitted COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

Abstract

Background COVID‐19 disease‐related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID‐19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. Methods We did a systematic review and meta‐analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID‐19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo‐controlled trials were included. Analyses of data were conducted using the Mantel–Haenszel random‐effects model (DerSimonian–Laird analysis). The study is registered with PROSPERO (CRD42021265948). Results We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID‐19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 –0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 –0%]. Conclusion Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk–benefit ratio must be considered while using either of them.

Thrombo‐inflammatory response in hospitalised patients with COVID‐19: a single institution experience

“…33 However, major bleeding developed in 5.4% of patients receiving anticoagulation dose compared with only 2.2% of patients receiving prophylactic dose. 33 Even though our study period occurred before official recommendations were introduced for therapeutic anticoagulation dose in severe COVID-19, 9.2% of patients received higher than prophylactic doses of anticoagulation. The recommendations for anticoagulation dose in severe (or acute) COVID-19 are being regularly updated.…”

“…The REMAP‐CAP trial identified a benefit of increased anticoagulation dose in preventing VTE in non‐ICU patients with COVID‐19 32 . A recent meta‐analysis of three randomised trials comparing prophylactic with therapeutic dose anticoagulation in hospitalised patients with COVID‐19 found that the incidence of VTE was 10% in the prophylactic group and 7% in the anticoagulation group 33 . However, major bleeding developed in 5.4% of patients receiving anticoagulation dose compared with only 2.2% of patients receiving prophylactic dose 33 .…”

Anticoagulant treatment and COVID‐19 mortality among older adults living in nursing homes in Sweden

“…AC treatment in COVID‐19 is one pertinent example where scientific evidence is lacking. There is evidence from both observational 9,25 and randomized clinical studies 10,11 supporting the benefits of heparin‐based ACs in middle‐aged individuals hospitalized with COVID‐19, but such data on older and frail individuals, or individuals residing in NHs is scant. A retrospective cohort study evaluated AC as one of several interventions in COVID‐19 in 133 individuals with a mean age of 87 years, at three NH facilities in France 24 .…”

“…Meta‐analyses indicate that venous thromboembolism (VTE) occurs in between 15% and 30% of individuals hospitalized with COVID‐19 6,7 . The benefits of initiating anticoagulants (AC) in individuals affected with COVID‐19 was recognized early in the pandemic 8 and the protective effect has since been confirmed in systematic reviews of both observational and randomized clinical trials 9–11 . Published studies to date include mainly middle‐aged individuals in inpatient or intensive care, 8–10,12,13 and scientific evidence on AC treatment in COVID‐19 among older individuals residing in NHs is scarce.…”

High-Dose Prophylactic Anticoagulation for COVID-19 Pneumonia: A Review of Benefits and Risks

“…These patients may include those with pre-existing risk factors for thromboembolism, such as obesity, advanced age, and comorbidities like heart disease or cancer. Additionally, patients admitted to the ICU or requiring mechanical ventilation may also be at high risk for thrombotic events and would benefit from prophylactic anticoagulation therapy [14,15].…”