OC 48.4 - Comparative Effectiveness of Alternative Bridging Therapies for Subtherapeutic INR in Ambulatory Patients with Left Ventricular Assist Devices

Background: Patients with left ventricular assist devices (LVAD) use warfarin to prevent life-threatening thromboembolic complications. Warfarin’s anticoagulant effects are notoriously variable, requiring the use of temporary “bridging” anticoagulation when subtherapeutic. Comparative effectiveness data between hospitalization for unfractionated heparin (UFH) and outpatient management with low-molecular-weight heparin (LMWH) are lacking.

Aims: To compare 30-day rates of bleeding and thrombotic events between patients bridged with LMWH vs UFH for subtherapeutic INR occurring in the outpatient setting.

Methods: We conducted a retrospective cohort study of patients aged 18 years and older with LVAD implantation between January 1, 2014 and December 31, 2018 from two academic medical centers. Data were collected for each unintended subtherapeutic international normalized ratio (INR) episode occurring in the ambulatory setting for which either UFH or LMWH was used. Patients were followed for 30 days after UFH or LMWH was discontinued, assessing for bleeding and/or thromboembolic events. Given multiple bridging episodes per patient, multivariable logistic regression analysis adjusted for site- and patient-level clustering along with LVAD type and HAS-BLED score. The composite outcome was major bleeding or thromboembolism.

Results: Data were collected from 269 patients and 1438 bridging episodes. Compared to HeartMate 3, having a HeartMate II LVAD (OR: 0.34; 95% CI: 0.15-0.81; p=0.015) or Heartware HVAD (OR: 0.24; 95% CI: 0.14-0.44; p< 0.001) was associated with lower odds of LMWH use. The 30-day rate of major bleeding or thromboembolism was lower for patients receiving LMWH as compared to UFH (11/1169 [0.9%] vs. 8/195 [4.1%], adjusted OR: 0.31; 95% CI: 0.11-0.87; p=0.026).

Conclusion(s): Outpatient LMWH bridging was associated with a lower risk of major adverse events for LVAD patients with subtherapeutic INR, compared to intravenous UFH therapy. If confirmed in prospective analyses, use of LMWH bridging as compared to hospital admission for UFH bridging is a potentially safer and lower-cost management strategy for this high-risk population.