# Systematic review of venous thromboembolism (VTE) occurrence in hospitalized patients receiving prophylactic unfractionated heparin twice vs. three times daily

## TL;DR

This study compares the effectiveness and safety of twice-daily and three-times-daily heparin regimens for preventing blood clots in hospitalized patients.

## Contribution

The study provides a systematic review of VTE and bleeding outcomes for different heparin dosing frequencies in hospitalized adults.

## Key findings

- TID UFH regimens had fewer VTE events (3.1%) compared to BID regimens (4.0%).
- TID regimens showed more bleeding events (4.3%) than BID regimens (3.2%).
- Higher quality studies suggest BID dosing may be more appropriate for general medical populations.

## Abstract

Guidelines recommend 5000U subcutaneous unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in acutely ill hospitalized adults, but data comparing dosing frequencies is limited. This systematic review aimed to compare VTE and bleeding outcomes between twice daily (BID) and three times daily (TID) UFH regimens. A literature search was completed on 3/7/2024. The primary outcome was VTE occurrence (deep vein thrombosis (DVT) or pulmonary embolism (PE)). Secondary outcomes included bleeding events. Studies reporting any relevant outcomes were included, while non-human studies, reviews, non-English texts, and high VTE risk populations were excluded. Risk of bias was assessed using the Cochrane Risk-of-Bias or Newcastle-Ottawa Quality Assessment Form. Data were synthesized using Covidence and Excel. After screening, 24 studies were included: 9 observational and 15 randomized studies. Regimens with TID UFH had a 3.1% VTE occurrence (12 studies, n = 145/4653) compared to 4.0% with BID regimens (9 studies, n = 218/5426). Three times daily regimens demonstrated 4.8% DVTs (11 studies, n = 244/5102) and 0.4% PEs (11 studies, n = 24/5372), compared to 9.7% DVTs (11 studies, n = 199/2062) and 0.9% PEs (9 studies, n = 17/1974) with BID regimens. Bleeding events occurred in 3.2% of patients with BID (9 studies, n = 196/6080) and 4.3% with TID regimens (13 studies, n = 393/9044). Three times daily UFH regimens led to fewer VTE, DVT, and PE events but more bleeding compared to BID. Newer data suggests BID dosing may be more appropriate for general medical populations. Limitations include variability in data quality and publication dates. Registered with PROSPERO. No funding was received.

• Current guidelines recommend no preference between BID or TID 5000U SC UFH for VTE prophylaxis in acutely ill hospitalized adult patients on medical floors.

• In this systematic review, patients on TID regimens experienced fewer VTEs (3.1%) but more bleeds (4.3%) than patients on BID regimens (4.0% VTEs, 3.2% any bleed).

• In the subgroup analysis of higher quality studies, contemporary good quality observational data showed similar and lower occurrence of VTE between regimens (1.7% TID, 1.2% BID), with sustained differences in any bleeding occurrence.

• In the majority of acutely ill hospitalized adults, BID regimens may be appropriate to balance thrombotic and bleeding risk. However, the increased thrombotic burden in patients admitted to medical floors with acute MI or stroke may warrant TID dosing.

• This review highlights the importance of the publication of newer observational studies comparing VTE prophylactic regimens to assess patient outcomes of VTE and bleeding in current practice.