PB0029 - Bridging therapy and risk of major bleeding and thrombosis with continuous-flow left ventricular assist device: a quasi-experimental study

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Eleonora Camilleri, MD

MD PhD student
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands

Co-Author(s)

RR

Robin P.W. Roovers

BSc Pharmacy student
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
EJ

Eva Janssen

MD, PhD student
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
MP

Meindert Palmen

MD PhD
Department of Thoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
JJ

J. Wouter Jukema

Prof MD PhD
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
Nienke van Rein, PharmD PhD

Post doc, PhD PharmD
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
LT

Laurens F. Tops

MD PhD
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands

Background: Bridging with low molecular weight heparin (LMWH) is recommended in continuous-flow left ventricular assist device (CF-LVAD) patients during subtherapeutic anticoagulation. However, the consequence of bridging on the risk of bleeding and thrombosis are unknown.

Aims: To assess the risk of major bleeding and thrombosis associated with bridging in CF-LVAD patients, through a regression discontinuity (RD) design.

Methods: We included CF-LVAD patients implanted at Leiden University Medical Center between 2010-2021. Outcomes were major bleeding (Interagency Registry for Mechanically Assisted Circulatory Support[INTERMACS] type 3, 4, 5) and thromboembolic events (pump thrombosis, arterial non-central nervous system and venous thromboembolism). We estimated incidence rates and hazard ratios (HR) with 95% confidence intervals (95%CI) by time-dependent Cox regression. Using a RD design, we compared patients using LMWH due to a subtherapeutic international normalized ratio (INR) to patients with no LMWH and an INR just in target range. As LMWH is initiated based on an INR below target range and INR is subject to random variability, patients just below and in the INR target range are comparable, mimicking a randomized trial. Analyses were performed including INRs±0.1, ±0.2, ±0.3, ±0.4 and ±0.5 around the INR threshold.

Results: 77 patients were included, with a median age of 69 years, 60(78%) were male and 35 (45%) had INTERMACS classification 3. We included 35,466 INRs during 91 patient-years of follow-up. Bridging was associated with increased major bleeding rates in all analyses (Figure 1). In particular, the risk of major bleeding was 6.7-fold increased (95%CI 1.2-38.0) during bridging compared to non-bridging considering INR+0.1, and 3.4-fold (95%CI 1.4-8.2) considering INR±0.5 (Figure 2A). While thrombotic events were infrequent, bridging showed a trend towards increased risk of thrombosis (HR up to 6.6, 95%CI 0.9-47.3, Figure 2B).

Conclusion(s): During bridging with LMWH, CF-LVAD patients had a 6.7-fold increased risk of major bleeding and a potential increased risk of thrombosis.