Perioperative Bridging Therapy With Unfractionated Heparin or Low-Molecular-Weight Heparin in Patients With Mechanical Prosthetic Heart Valves on Long-Term Oral Anticoagulants (from the REGIMEN Registry)

doi:10.1016/j.amjcard.2008.05.042

The American Journal of Cardiology

Volume 102, Issue 7, 1 October 2008, Pages 883-889

https://doi.org/10.1016/j.amjcard.2008.05.042 Get rights and content

Patients with mechanical prosthetic heart valves require long-term oral anticoagulant therapy (OAT). During the temporary interruption of OAT, bridging anticoagulant therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended. This prespecified subgroup analysis from REGIMEN—a large, prospective, multicenter registry—compared UFH (n = 73) and LMWH (n = 172) as bridging anticoagulation in patients with mechanical heart valves on long-term OAT. Patient demographics and co-morbidities were generally similar between groups. There were more bileaflet valves in the LMWH group (67.4% vs 43.8%, p = 0.0005), but no differences in valve positions between groups. The LMWH group was less likely to undergo major surgery (33.7% vs 58.9%, p = 0.0002) and cardiothoracic surgery (7.6% vs 19.2%, p = 0.008), and to receive intraprocedural anticoagulants or thrombolytics (4.1% vs 13.7%, p = 0.007). Major adverse event rates (5.5% vs 10.3%, p = 0.23) and major bleeds (4.2% vs 8.8%, p = 0.17) were similar in the LMWH and UFH groups, respectively; 1 arterial thromboembolic event occurred in each group. More LMWH-bridged patients were treated as outpatients or discharged from the hospital in <24 hours (68.6% vs 6.8%, p <0.0001). Multivariate logistic analysis found no significant differences in major bleeds and major composite adverse events when adjusting for cardiothoracic or major surgery between groups. In conclusion, for patients with mechanical prosthetic heart valves on long-term OAT, mostly outpatient-based LMWH bridging therapy appears to be feasible for selected procedures, is as safe as UFH, and is associated with a low arterial thromboembolic rate.

Section snippets

Methods

REGIMEN was a large, observational, prospective, multicenter registry in the United States and Canada that prospectively enrolled consecutive patients on long-term OAT who required bridging anticoagulant therapy for an elective surgical procedure from July 1, 2002 to December 31, 2003. It was approved by the Institutional Review Boards of each participating site. All patients gave written informed consent for their data to be used.

The full REGIMEN methodology has been described previously.⁶

Results

Of 1,077 patients requiring bridging therapy for an elective procedure, a total of 245 patients were on long-term OAT because they had MHV replacement. Baseline patient demographics are listed in Table 1. The mean age of the patients in both treatment groups was approximately 65 years, and patients bridged with LMWH were more likely to be men compared with those receiving UFH (66% vs 54%, respectively, p = 0.03). There were no differences in valve position (aortic, mitral, or both) between

Discussion

This study is the first large, prospective, multicenter registry to directly compare practice patterns and outcomes of UFH- and LMWH-bridging therapy in patients with MHVs on long-term OAT requiring temporary interruption for an elective surgery or invasive procedure. Although UFH has previously been used as bridging therapy in patients with MHVs, necessitating hospital admission,¹⁰ there has been reluctance in physicians in North America to use LMWH—specifically enoxaparin—as bridging therapy

Acknowledgment

An independent statistical analysis was conducted by Hans Petersen, Associate Director, Center for Pharmacoeconomic and Outcomes Research, Albuquerque, New Mexico. No individual compensation was received for conducting the analysis.

References (21)

J.M. Spandorfer et al.
Use of enoxaparin for the chronically anticoagulated patient before and after procedures
Am J Cardiol
(1999)
A.C. Spyropoulos et al.
Clinical outcomes with unfractionated heparin or low-molecularweight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry
J Thromb Haemost
(2006)
M. Charlson et al.
Validation of a combined comorbidity index
J Clin Epidemiol
(1994)
R.J. Beyth et al.
Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin
Am J Med
(1998)
R.E. Katholi et al.
The management of anticoagulation during noncardiac operations in patients with prosthetic heart valves: a prospective study
Am Heart J
(1978)
K.M. Halbritter et al.
Bridging anticoagulation for patients on long-term vitamin-K-antagonists: a prospective 1 year registry of 311 episodes
J Thromb Haemost
(2005)
A.C. Spyropoulos et al.
Costs and clinical outcomes associated with low-molecular-weight heparin vs unfractionated heparin for perioperative bridging in patients receiving long-term oral anticoagulant therapy
Chest
(2004)
A.C. Spyropoulos et al.
A disease management protocol for outpatient perioperative bridge therapy with enoxaparin in patients requiring temporary interruption of long-term oral anticoagulation
Pharmacotherapy
(2004)
A.H. Tinmouth et al.
Dalteparin as periprocedure anticoagulation for patients in warfarin and at high risk of thrombosis
Ann Pharmacother
(2001)
I. Ferreira et al.
Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol
Heart
(2003)

There are more references available in the full text version of this article.

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In a meta-analysis of non-randomized studies totaling 12,278 patients that compared bridging vs no bridging in a mixed population of patients, of whom 24% had a mechanical heart valve, there was no significant difference in the risk of ATE in bridged and non-bridged groups (OR = 0.80; 95% CI: 0.42-1.54), but bridging conferred an increased risk of major bleeding (OR = 3.60; 95% CI: 1.52-8.50).23 In non-randomized studies in which all patients with a mechanical heart valve received perioperative therapeutic-dose heparin bridging, this approach was associated with a pooled incidence of ATE and major bleeding of 0.9% (95% CI: 0.2-1.5) and 2.8% (0.8-4.8), respectively.56,86-88,107-109 5.
The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug.
Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines.
A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures.
Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.
Society for Maternal-Fetal Medicine Consult Series #61: Anticoagulation in pregnant patients with cardiac disease
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Although LMWH may be desirable because it can be taken as an outpatient, transitions between anticoagulation agents should be performed on an inpatient rather than an outpatient basis to allow for faster achievement of therapeutic values and a decrease in dosage fluctuations. We suggest reinitiation of IV UFH after delivery with the concomitant transition back to warfarin in the inpatient setting for ongoing therapeutic anticoagulation (GRADE 2C).62–65 Thrombosis of a mechanical heart valve is a life-threatening complication requiring immediate treatment.
Pregnancy in individuals with a mechanical heart valve has been classified as very high risk because of a substantially increased risk of maternal mortality or severe morbidity. Lifelong therapeutic anticoagulation is a principal component of the medical management of mechanical heart valves to prevent valve thrombosis. Anticoagulation regimens indicated outside of pregnancy for patients with mechanical valves should be continued during pregnancy with the possibility of modifications based on the type of valve, the trimester of pregnancy, individual risk tolerance, and circumstances around the time of delivery. The purpose of this document is to provide recommendations regarding the management of anticoagulation for common cardiac conditions complicating pregnancy, including mechanical heart valves, atrial fibrillation, systolic heart failure, and congenital heart disease.
2021 ESC/EACTS Guideline on the diagnosis and treatment of valvular heart disease: Developed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Working Groups on the diagnosis and treatment of valvular heart disease
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Prophylactic doses of low-molecular weight heparin as periprocedural bridging therapy in mechanical heart valve patients
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The cumulative incidence for MBEs related to periprocedural bridging therapies was 1.3% in our study. Other studies using therapeutic doses of LMWH showed a rate of MBEs ranging from 0.86–19%, most of the studies demonstrating rates between 3.2 and 4.2% [4–8,10,12]. The only study including prophylactic doses of LMWH had an 8% rate of major bleeding events.
Mechanical heart valve (MHV) patients undergoing invasive procedures necessitating an interruption of their lifelong anticoagulant therapy, often require bridging with low-molecular weight heparin (LMWH) or unfractionated heparin. The aim of this study was to assess whether bridging MHV patients with prophylactic doses of LMWH undergoing invasive, elective procedures is a safe and effective method.
This observational cohort study included all MHV patients on vitamin K anticoagulant therapy in Malmö, registered and monitored via AuriculA (the Swedish national quality registry for atrial fibrillation and anticoagulation), between 1/1/2008 and 31/12/2011. Inclusion criteria were periprocedural bridging therapies conducted via AuriculA. Primary endpoints were mortality, thromboembolic (TE) events or major bleedings (MBE) within 30 days of bridging.
During the study period, 210 patients had undergone 434 bridging therapies managed via AuriculA; 203 due to subtherapeutic INR-values were excluded. The remaining 231 periprocedural bridging therapies were included. All were bridged with prophylactic doses of LMWH. When comparing patients with aortic and/or mitral valve replacements undergoing low- or high-risk interventions, only number of days bridged for a low-risk intervention differed significantly. Patients with a mitral or mitral and aortic valve replacement were bridged for a longer period (p = 0.023). No TE events, 1 death (0.4%) and 3 MBEs (1.3%) occurred related to periprocedural bridging.
Our study shows a low rate of MBEs, deaths and no TE events when bridging MHV patients undergoing invasive, elective procedures with prophylactic doses of LMWH.

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: This study was funded by an unrestricted grant from sanofi-aventis, New Jersey, United States. The authors received editorial support in the preparation of this manuscript, funded by sanofi-aventis. The authors were fully responsible for content and editorial decisions for this manuscript. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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Valvular heart diseasePerioperative Bridging Therapy With Unfractionated Heparin or Low-Molecular-Weight Heparin in Patients With Mechanical Prosthetic Heart Valves on Long-Term Oral Anticoagulants (from the REGIMEN Registry)

Section snippets

Methods

Results

Discussion

Acknowledgment

Am J Cardiol

J Thromb Haemost

J Clin Epidemiol

Am J Med

Am Heart J

J Thromb Haemost

Chest

A disease management protocol for outpatient perioperative bridge therapy with enoxaparin in patients requiring temporary interruption of long-term oral anticoagulation

Pharmacotherapy

Dalteparin as periprocedure anticoagulation for patients in warfarin and at high risk of thrombosis

Ann Pharmacother

Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol

Heart

Valvular heart disease
Perioperative Bridging Therapy With Unfractionated Heparin or Low-Molecular-Weight Heparin in Patients With Mechanical Prosthetic Heart Valves on Long-Term Oral Anticoagulants (from the REGIMEN Registry)