Optimal initial duration of low molecular weight heparin lead-in before direct oral anticoagulants for short-term outcomes of hospitalized patients with non-high-risk acute pulmonary embolism

Abstract

Abstract Background There are currently three strategies for the duration of low molecular weight heparin (LMWH) lead-in before direct oral anticoagulants (DOACs) in patients with acute pulmonary embolism (PE): one is at least 5 days, the other is at least 3 days and the last one is less than 3 days. Which one is the best is yet unknown. Aim To explore optimal initial duration of LMWH lead-in before DOACs for short-term outcomes of hospitalized patients with non-high-risk acute PE. Design Retrospective observational cohort study using propensity score matching. Methods We divided non-high-risk PE patients into short-LMWH (LMWH <3 days), intermediate-LMWH (LMWH 3-5 days) and long-LMWH (LMWH >5 days) groups, in a 1:1:2 ratio by using propensity score matching. Primary outcomes were a composite of mortality including all-cause and PE-related mortality, VTE recurrence and major bleeding, as well as each one of them, at 3-month after PE diagnosis. Results The short-LMWH group (N = 504) had higher 3-month composite primary outcome (129 [25.6%] vs. 67 [13.3%], P < 0.001), all-cause mortality (112 [22.2%] vs. 39 [7.7%], P < 0.001) and PE-related mortality (48 [9.5%] vs. 17 [3.4%], P < 0.001), than the intermediate-LMWH group (N = 504). The short-LMWH group also had higher 3-month composite primary outcome (129 [25.6%] vs. 151 [15.0%], P < 0.001), all-cause mortality (112 [22.2%] vs. 90 [8.9%], P < 0.001) and PE-related mortality (48 [9.5%] vs. 41 [4.1%], P < 0.001) than the long-LMWH group (N = 1008). The VTE recurrence and major bleeding rates were similar between the short-LMWH and intermediate-LMWH groups, and between the short-LMWH and long-LMWH groups. The intermediate-LMWH and long-LMWH groups had similar 3-month primary outcomes rates in whole or in part with each other. Conclusions For patients with non-high-risk acute PE, the optimal duration of initial LMWH lead-in before switching to DOACs could be 3–5 days.