Risk of Developing Post Thrombotic Syndrome after Deep Vein Thrombosis with Different Anticoagulant Regimens, a Systematic Review and Pooled Analysis

Background

Post-thrombotic syndrome (PTS) is a chronic condition that arises in up to 20-50% of patients with deep vein thrombosis (DVT) of the lower extremity. Symptoms range from skin color changes and limb heaviness to edema, chronic pain and ulcers. PTS has a significant impact on patients' quality of life. Hence, it is important to optimize DVT management to minimize the incidence and severity of PTS. It is unclear if different anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS.

Objective

We sought to assess the incidence rates of PTS development after a proximal DVT of the lower extremity managed with different anticoagulation regimens.

Methods

A systematic search of MEDLINE, EMBASE and PubMed as well as conference proceedings (inception to June 2023) was performed. Studies were screened and selected if they met the criteria for patients (age ≥18) receiving anticoagulation therapy for a minimum of 3 months after the diagnosis of a proximal DVT of the lower extremity. The primary outcome was development of PTS defined by the Villalta or PRV score of ≥ 5, or as defined by the individual studies. Incidence rates (overall and per type of anticoagulant regimens) were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95% confidence intervals (CI) using R software.

Results

Out of the 2837 identified studies, 77 were reviewed in full text and 21 (n= 4342 patients) were included in the analysis (7 randomized controlled trials, 14 observational studies). There were 17 studies (2834 patients), 12 studies (1212 patients) and 2 studies (296 patients) reporting the outcomes for VKA, DOAC and LMWH, respectively. The crude incidence rates for PTS development are depicted in Figure 1. After adjusting for duration of anticoagulation, the overall incidence of PTS was 16.3 per 100 patient-years (95% CI: 11.1-24.12). The incidence of PTS was 15.1 per 100-patient-years (95% CI: 8.7-26.1), 18.2 per 100 patient-years (95% CI: 9.4-35.1), 24.6 per 100 patient-years (95% CI: 9.2-65.5) for VKA, DOAC and LMWH, respectively. The most used DOAC was rivaroxaban (incidence rate of 12.3 per 100 patient-years (95% CI: 1.6-96.4)).

Conclusions

PTS is a common complication among patients with proximal DVT of the lower extremity. Incidence of PTS development may differ based on the anticoagulant regimen. DOACs seems to be associated with lower incidence PTS development compared to VKA and LMWH. Future clinical trials are needed to confirm these findings.