Can Enoxaparin Be Used as a Bridge to Warfarin for Outpatients With LVADs?

The use of the low-molecular-weight heparin (LMWH) enoxaparin as a bridge to warfarin in outpatients with a left ventricular assist device (LVAD) can be well tolerated and is associated with low risk of major bleeding and thrombosis. That’s the conclusion of a retrospective analysis of Cleveland Clinic outpatients who received a variety of devices over a three-year period. Outcomes were particularly favorable with the HeartMate 3 (HM3), currently the only LVAD commercially available in the U.S.

The study was published in Artificial Organs (2024;48[4]:386-391).

“Our findings support the use of enoxaparin for bridging outpatients with an LVAD to warfarin, an area in which current guidance is lacking,” says Cleveland Clinic heart failure cardiologist Sanjeeb Bhattacharya, MD, a co-author of the study. “We found no thrombotic events in patients with an HM3 device, even using a low enoxaparin dose, although there was one major bleeding event in a very high-risk patient.”

LMWH bridging in need of study

Any LVAD is associated with risks of both thrombosis and bleeding, making it imperative to determine optimal strategies for anticoagulation therapy. Joint guidelines from the American Association for Thoracic Surgery and the International Society of Heart and Lung Transplantation recommend intravenous unfractionated heparin for bridging hospitalized patients with an LVAD until they can safely begin warfarin, but possible approaches for the use of LMWHs — which can be administered subcutaneously — in the outpatient setting are unclear.

Other studies have suggested that enoxaparin bridging is feasible, but the studies have been small or primarily investigated the strategy with earlier devices — i.e., the HeartWare Ventricular Assist Device (HVAD) and HeartMate II (HM2).

The current study, which retrospectively analyzed the use of enoxaparin bridging in Cleveland Clinic outpatients receiving an LVAD, included a larger population of HM3 recipients and focused particular attention on enoxaparin dosing and duration along with clinical outcomes.

Study population, device and enoxaparin use

The study cohort consisted of 49 Cleveland Clinic LVAD outpatients (54 bridging episodes) who received enoxaparin bridging from January 2018 through July 2021. Mean age was 58 years, and most patients were male (83.6%). Comorbidities included atrial fibrillation (53.0%), chronic kidney disease (59.2%), history of major bleed (32.6%), prior stroke (28.6%) and history of venous thromboembolism (28.6%). Most bridging episodes (78%) involved concomitant aspirin use.

Devices used were as follows:

• HVAD (12 patients, 12 bridging episodes)
• HM2 (10 patients, 11 bridging episodes)
• HM3 (27 patients, 31 bridging episodes)

Mean INR was 1.3 at the time of enoxaparin initiation.

Most patients with an HM2 or HVAD received enoxaparin 1 mg/kg every 12 hours. Among bridging episodes involving HM3:

• 13 patients (42%) received 1 mg/kg every 12 hours.
• 13 patients (42%) received 0.5 mg/kg every 12 hours.
• 5 patients (16%) received between 0.5 and 1 mg/kg every 12 hours.

Median duration of bridging in the entire cohort was 6 days (interquartile range, 4-8).

Outcomes

Major bleeding was assessed during bridging and up to seven days after enoxaparin discontinuation. One event occurred in the cohort (1.9%), in a patient with an HM3. The patient was 73 years old and had a history of gastrointestinal bleeding. The INR was 1.2 at the time of the event. Medications were aspirin and enoxaparin 1 mg/kg every 12 hours. The patient died from complications of bleeding within one month of hospitalization.

Thrombotic events occurred only in patients with an HVAD or HM2 and included the following:

• Pump thrombosis requiring pump exchange occurred in two patients (3.7%), both of whom died. One had an HVAD (INR 2.3) and one had an HM2 (INR 1.8). Both patients received enoxaparin 1 mg/kg every 12 hours and were taking either aspirin or clopidogrel.
• Ischemic stroke occurred in two patients (3.7%), both of whom received an HVAD (INR 2.0 and undetermined) and were taking enoxaparin 1 mg/kg every 12 hours.

Mortality within 30 days of enoxaparin initiation occurred in a total of three patients (6.1%).

Enoxaparin bridging strategy merits further study

“Short-term enoxaparin bridging appears to be a feasible approach for LVAD outpatients and merits more study,” Dr. Bhattacharya concludes.

His colleague Michael Tong, MD, Director of Cardiac Transplantation and Mechanical Circulatory Support, says the stakes of this issue can be high for individual patients as well as the healthcare system. “Bridging patients with enoxaparin rather than heparin allows us to decrease the number of days that patients need to unnecessarily stay in the hospital,” says Dr. Tong, a cardiac surgeon who was not involved in the study. “For some patients, that can add to up to one week per year.”

Dr. Bhattacharya notes that an important unresolved issue isenoxaparin dosing. Although the standard dosage is 1 mg/kg every 12 hours, no bleeding or thrombotic events occurred in study patients receiving less than that. He adds that the occurrence of minor bleeding events should also be evaluated, which this study was unable to do.

“Larger prospective studies comparing different bridging strategies are warranted to further define the best approach,” adds co-author Ran Lee, MD, a heart failure and critical care cardiologist. “Dosing, duration of bridging and optimal INR thresholds for initiating and discontinuing the drug need to be evaluated to determine best-practice guidelines for this important issue.”