Perioperative bridging interruption with heparin for the patient receiving long-term anticoagulation

PURPOSE OF REVIEW: To provide a timely and concise review of the most recent clinical data in the field of bridging (anticoagulation) therapy with heparin for the at-risk patient receiving long-term oral anticoagulation who requires temporary interruption for an elective invasive procedure or surgery. RECENT FINDINGS: A recent systematic review found that the quality of studies of bridging therapy published before June 2001 was generally poor. More recent larger prospective cohort studies and registries of patients receiving long-term oral anticoagulation, including patients with mechanical heart valves, who underwent bridging therapy with mostly treatment-dose low-molecular-weight heparin for both major and non-major elective invasive procedures or surgeries have been completed. These studies reveal an overall thromboembolic complication rate of 1.22 (95% CI 0.81-1.77) and an overall major bleed rate of 2.94 (95% CI 2.28-3.74). Standardized low-molecular-weight heparin bridging regimens using postoperative bleeding risk assessments optimized good clinical outcomes, and bridging therapy with low-molecular-weight heparin appears to be at least as safe as unfractionated heparin and produces substantial cost savings through reduction in length of stay in the hospital. SUMMARY: Perioperative bridging therapy with heparin, either unfractionated heparin or low-molecular-weight heparin, appears to be safe and effective for patients, including those with mechanical heart valves, receiving long-term oral anticoagulation who require temporary interruption, especially for non-high-bleeding risk procedures such as minor surgery and invasive procedures. Further studies, including randomized double-blind placebo-controlled trials, are needed to optimize bridging therapy for specific patients and procedures.     

Cost analysis of "bridging therapy" with low-molecular-weight heparin versus unfractionated heparin during temporary interruption of chronic anticoagulation

Patients on long-term anticoagulation who require interruption of therapy for surgery may receive "bridging therapy" with continuous-infusion unfractionated heparin or low-molecular-weight heparin (LMWH). We estimated the costs of bridging therapy with: (1) LMWH self-administered at home, (2) LMWH administered by a nurse to patients at home, and (3) continuous-infusion unfractionated heparin in the hospital. For surgeries requiring an overnight stay, bridging costs are estimated to be 672, 933, and 3,816 US dollars, respectively, for each of these strategies.     

Excessive anticoagulation in patients with mild renal insufficiency receiving long-term therapeutic enoxaparin

Low-molecular-weight heparins, such as enoxaparin, are increasingly being used for treatment of venous thromboembolism. We describe two patients who received therapeutic enoxaparin for several months. Although their serum creatinine values were normal, both had mild renal insufficiency (creatinine clearance 60-70 ml/min), and both accumulated the drug abnormally and experienced clinical bleeding. These results suggest that patients receiving enoxaparin (or other low-molecular-weight heparins) in therapeutic doses for periods of more than 4 weeks should be considered for laboratory monitoring to avoid bleeding.     

Comparison of pain and ecchymosis with low-molecular-weight heparin vs. unfractionated heparin in patients requiring bridging anticoagulation after warfarin interruption: a randomized trial

Background Subcutaneous (SC) low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) are safe and efficacious for bridging anticoagulation after warfarin interruption. Although LMWH and UFH are self-administered by >90% of patients, factors that may be important to patients such as differences in pain and ecchymosis have not been explored. Methods We randomized 24 patients to receive SC LMWH or SC UFH twice-daily during the perioperative period. Injection associated pain was recorded using a visual analogue scale and area of ecchymosis was measured by digital photography of the injection site on the day of the procedure. Results The area of ecchymosis was 2-fold higher with UFH than LMWH (19.4 cm² vs. 8.98 cm²; P = 0.33) and pain was similar with both treatments (115 mm vs. 171 mm; P = 0.25), though neither finding attained statistical significance. Conclusions This exploratory study was underpowered to detect differences between the groups. Further studies are needed to reliably compare pain and ecchymosis in LMWH vs. UFH.     

Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy： Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.     

Contractile response and mitral regurgitation after temporary interruption of long-term cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BVP) is a promising treatment modality for symptomatic patients with chronic left ventricular (LV) systolic dysfunction and intraventricular conduction delay. Clinical studies have shown short-term improvement in contractile function and mid-term improvement in clinical status with CRT. The objective of this study was to evaluate the haemodynamic consequences of temporary interruption of CRT after long-term stimulation. METHODS AND RESULTS: Twenty patients (16 men, 4 women) with LV dysfunction and New York Heart Association class III or IV heart failure, despite optimal medical therapy and a QRS interval of at least 120 ms, received a transvenous BVP system at the age of 66 (interquartile range, 61-69). Patients were studied after a median duration of 427 days (interquartile range, 281-563) of continuous CRT and again 72 h after cessation of BVP. Withdrawal of CRT resulted in a significant decline in maximal rate of LV systolic pressure rise from 711 mmHg/s (interquartile range, 640-816) to 442 mmHg/s (interquartile range, 389-582) (P=0.0001) and increases in mitral effective regurgitant orifice area from 4.8 mm(2) (interquartile range, 0.0-7.8) to 9.1 mm(2) (interquartile range, 5.7-13.3) (P=0.0001), mitral regurgitant volume from 7.8 mL (interquartile range, 0.0-11.5) to 16.0 mL (interquartile range, 10.7-20.8) (P=0.0001) and fraction from 13.8% (interquartile range, 0.0-19.2) to 27.7% (interquartile range, 14.6-34.0) (P=0.0002) determined by Doppler echocardiography. CONCLUSION: Cessation of long-term BVP leads to a decline in LV systolic performance and an increase in functional mitral regurgitation. These results indicate a sustained benefit of long-term CRT and support the notion to maintain CRT indefinitely.     

Long-term oral anticoagulation therapy of peripheral arterial disease.

This review article summarizes clinical data on adjuvant long-term oral anticoagulation therapy (OAC) of peripheral arterial disease (PAD). It analyzes the underlying risk model of oral anticoagulation. Definitions of runoff patterns, of major and minor bleeding complications, of predictors of major bleedings as well as a classification of patient risk groups are described. The indication for OAC treatment of chronic limb ischemia remains still due to an individual decision. Clinical decision making is facilitated by the risk model. Improved oral anticoagulation control results in fewer bleeding complications. Studies on patient weekly self-testing and self-dosing which support this hypothesis are reviewed in the context of adjuvant OAC therapy.     

Optimizing selection of antithrombotic therapy in patients requiring PCI and long term anticoagulation

There remains clinical equipoise in the appropriate selection of antiplatelet therapy for the patient on long-term anticoagulation requiring percutaneous coronary intervention. Since most of these patients represent an increasingly aging population, the significant risk of thromboembolism and stent thrombosis must be weighed against the risk of major bleeding. This article reviews the current state of evidence to provide a framework for the practicing clinician.     

Costs and clinical outcomes associated with low-molecular-weight heparin vs unfractionated heparin for perioperative bridging in patients receiving long-term oral anticoagulant therapy

STUDY OBJECTIVES: There have been no health-care cost evaluations comparing the use of low-molecular-weight heparin (LMWH) to unfractionated heparin (UH) as "bridge therapy" in the perioperative period in patients receiving long-term oral anticoagulant (OAC) therapy who need interruption of therapy to undergo an elective surgical procedure. We performed a retrospective analysis of the medical and administrative records of health plan members in a managed care organization who underwent bridge therapy perioperatively with either i.v. UH, administered in a hospital setting, or LMWH, administered primarily in the outpatient setting using disease management guidelines. DESIGN: A retrospective analysis of medical and administrative records of treated health plan members meeting inclusion/exclusion criteria during the two study periods (ie, from 1994 to 1996 and from 1998 to 2000). SETTING: Staff-model health maintenance organization serving New Mexico. PATIENTS: The UH group included persons receiving long-term warfarin therapy from 1994 to 1996 (26 patients), and the LMWH group included persons receiving long-term warfarin therapy from 1998 to 2000 (40 patients) with perioperative use of heparin (either UH or LMWH) as bridge therapy for an elective surgical procedure. INTERVENTIONS: Costs were calculated for the period from 10 days before the procedure through 30 days after the procedure. The rates of adverse events (ie, valvular or mural thrombus, intracranial event, transient ischemic attack, peripheral arterial event, venous thromboembolic event, major and minor bleeding, thrombocytopenia, and death) occurring 1 to 30 days postprocedure were determined. MEASUREMENTS AND RESULTS: The groups were similar in age, sex, Charlson score, indication for long-term warfarin therapy (ie, arterial/cardiac vs venous), mean international normalized ratio prior to procedure, procedure duration, use of intraprocedural anticoagulant agents or thrombolytic agents, and use of general anesthesia during the procedure (all p > 0.05). A total of 34.6% of UH patients and 40.0% of LMWH patients experienced one or more clinical adverse events within 30 days of the postoperative period, a difference that was not statistically significant (p = 0.67). The mean total health-care costs were 31,625 dollars in the UH group and 18,511 dollars in the LMWH group (p < 0.01). The mean inpatient costs were 28,515 dollars in the UH group and 14,330 dollars in the LMWH group (p < 0.01). Outpatient surgery costs (1,159 dollars vs 53 dollars, respectively; p = 0.01) and pharmacy costs (639 dollars vs 133 dollars, respectively; p < 0.01) were higher in the LMWH group. CONCLUSIONS: The mean total health-care costs in the perioperative period were significantly lower (by 13,114 dollars) in patients receiving long-term OAC therapy using LMWH compared to those receiving it using UH for an elective surgical procedure. The cost savings associated with LMWH use were accomplished through the avoidance or minimization of inpatient stays and no increase in the overall rate of clinical adverse events in the postoperative period.     

Dual versus single antiplatelet therapy for patients with long-term oral anticoagulation undergoing coronary intervention: A systematic review and meta-analysis

Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for patients taking oral anticoagulation (OAC) after coronary intervention. Background The optimal regimen remains controversial patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for eligible studies including data of triple therapy (TT) versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE). The safety outcome was major bleeding. Results Fourteen studies with 32825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios (OR): 1.56, 95% confidence interval (CI): 0.98–2.49, P = 0.06] and a markedly higher risk of all-cause death (OR; 2.11, 95% CI: 1.10–4.06 P = 0.02) compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE (OR: 0.63, 95% CI: 051–0.77 P < 0.0001), all-cause death (OR: 0.45, 95% CI: 0.20–0.97, P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral embolism (PE) (OR: 0.29, 95% CI: 0.09–0.96, P = 0.04) compared with OAC plus aspirin.