Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study

Abstract

Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Lowmolecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS 2 (1 point for each of congestive heart failure, hypertension, age 75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA 2 DS 2 -VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

Heparin bridging therapy is not necessary for patients with atrial fibrillation undergoing temporary interruption of warfarin therapy for elective invasive procedures or surgery

“…[8][9][10][11] Notable studies included the recent 2017 article by Sjögren et al, a register-based cohort study, which focused on post-warfarin cessation all-cause mortality, bleeding, and thrombosis. 12 However, in this study, the type of procedure that prompted bridging was not known, limiting the generalizability of results. Also of mention, Steinberg et al analyzed results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective, observational registry study, and found that periprocedural bridging was associated with a higher occurrence of adverse events.…”

Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review

“…We also conducted pre-specified sensitivity analyses excluding conference abstracts or small studies (<100 procedures). Additional (not prespecified) sensitivity analyses were conducted: 1) excluding studies that did not specifically report outcomes for patients with prior venous thromboembolism, but could be included because no study patient experienced an outcome event, and 2) excluding a study 18 that used propensity score matching and weighting to equalize the number of patients in the exposure groups.…”

“…studies reported results that were unadjusted for potential confounding except for Sjögren et al, 18 where propensity score matching was used.…”

“…A C C E P T E D M A N U S C R I P T ‡ patients were randomly assigned to bridging or continuation of VKA in two studies, but none used random assignment to bridging vs. VKA interruption without bridging § Some studies implemented multiple strategies * includes major bleeding and any other bleeding outcomes that were specifically reported for patients with previous venous thromboembolism † in the study by Sjögren et al, 18 procedures in the non-bridging group were propensity score matched and weighted to equal the number of procedures in the bridging group; therefore, the number of procedures with bridging and without bridging does not add up to the exact number of overall procedures ‡ the non-integer number of outcome events (5.5 venous thromboembolic events) in the study by Sjögren et al was rounded to the next integer for this analysis. When rounding down to the next lower integer, the results were similar (pooled incidence 0.4%, 95%CI 0.3-0.7%)…”

Direct oral anticoagulants versus standard triple therapy in atrial fibrillation and PCI: meta-analysis

“…Finally, less is known about compliance, clinical profile of patients who experienced any events, drug-drug interaction and bridging with heparin in patients treated with warfarin, which is known to increase the risk thromboembolism 27…”