A tale of two centers: Is low-molecular-weight heparin really superior for prevention of posttraumatic venous thromboembolism?

BACKGROUND: Low-molecular-weight heparin (LMWH) is widely used for venous thromboembolism chemoprophylaxis following injury. However, unfractionated heparin (UFH) is a less expensive option. We compared LMWH and UFH for prevention of posttraumatic deep venous thrombosis (DVT) and pulmonary embolism (PE). METHODS: Trauma patients 15 years or older with at least one administration of venous thromboembolism chemoprophylaxis at two level I trauma centers with similar DVT-screening protocols were identified. Center 1 administered UFH every 8 hours for chemoprophylaxis, and center 2 used twice-daily antifactor Xa-adjusted LMWH. Clinical characteristics and primary chemoprophylaxis agent were evaluated in a two-level logistic regression model. Primary outcome was incidence of DVT and PE. RESULTS: There were 3,654 patients: 1,155 at center 1 and 2,499 at center 2. The unadjusted DVT rate at center 1 was lower than at center 2 (3.5% vs. 5.0%; p = 0.04); PE rates did not significantly differ (0.4% vs. 0.6%; p = 0.64). Patients at center 2 were older (mean, 50.3 vs. 47.3 years; p < 0.001) and had higher Injury Severity Scores (median, 10 vs. 9; p < 0.001), longer stays in the hospital (mean, 9.4 vs. 7.0 days; p < 0.001) and intensive care unit (mean, 3.0 vs. 1.3 days; p < 0.001), and a higher mortality rate (1.6% vs. 0.6%, p = 0.02) than patients at center 1. Center 1's patients received their first dose of chemoprophylaxis earlier than patients at center 2 (median, 1.0 vs. 1.7 days; p < 0.001). After risk adjustment and accounting for center effects, primary chemoprophylaxis agent was not associated with risk of DVT (odds ratio, 1.01; 95% confidence interval, 0.69-1.48; p = 0.949). Cost calculations showed that UFH was less expensive than LMWH. CONCLUSION: Primary utilization of UFH is not inferior to LMWH for posttraumatic DVT chemoprophylaxis and rates of PE are similar. Given that UFH is lower in cost, the choice of this chemoprophylaxis agent may have major economic implications. LEVEL OF EVIDENCE: Prognostic and epidemiological, level II; Therapeutic, level III.

The cost-effectiveness and cost-utility analysis of the use of enoxaparin compared with heparin for venous thromboembolism prophylaxis in medical inpatients in Iran.

BACKGROUND: Moderate to high risk medical inpatients are at increased risk of Venous Thromboembolism (VTE). The present study aims to investigate the cost-effectiveness and cost-utility of using Enoxaparin compared to Heparin in VTE prophylaxis in medical inpatients, from Iranian payer's perspective. METHODS: Decision tree modeling technique was used to evaluate cost-effectiveness and cost-utility of the compared interventions. The main considered outcomes were Life Years Gained (LYG) for Cost-Effectiveness Analysis (CEA) and Quality-Adjusted Life Years (QALY) for Cost-Utility Analysis (CUA). Costs and consequences of the interventions were evaluated for a three-month period and reported as Incremental Cost-Effectiveness Ratios (ICERs). One-way and Probabilistic Sensitivity Analysis (PSA) were conducted to evaluate the robustness of the model due to uncertainty in the input data. RESULTS: In base case scenario (i.e. public tariff), incremental cost was $10.32, and incremental QALY and incremental LYG were 0.0001 and 0.0002 per patients respectively. Base case ICERs were 60,376 USD/QALY and 71,077 USD/LYG per patient. The results of the sensitivity analysis showed the robustness of the model. CONCLUSION: As the estimated ICER per QALY is more than three times the reported Gross Domestic Product (GDP) per capita by world bank for Iran in 2017 ($5415), the use of Enoxaparin for VTE prophylaxis in medical in patients doesn't seem to be a cost-effective intervention compared to the use of Heparin in Iran.

Assessment of the adherence to and costs of the prophylaxis protocol for venous thromboembolism

OBJECTIVES: Evaluate adherence to the therapeutic prophylaxis protocol for venous thromboembolism (VTE) as well as the costs of this practice. METHODS: A descriptive and cross-sectional study was conducted at a State General Hospital in Brazil through reports of drug dispensions, prescriptions and risk stratification of patients. Adherence to the VTE prophylaxis protocol was monitored. The tests for VTE diagnosis measured the adherence to therapeutic prophylaxis treatment, and the purchase prices of the drugs went into the calculation of drug therapy costs. The level of adherence to prescriptions for VTE prophylaxis in the hospital was classified as "adherence", "non-adherence" and "justified non-adherence" when compared with the protocol. RESULTS: Protocol adherence was observed for 50 (30.9%) patients, and non-adherence was observed for 63 (38.9%) patients, generating an additional cost of $180.40/month. Justified non-adherence in 49 (30.2%) patients generated $514.71/month in savings due to a reduction in the number of daily administrations of unfractionated heparin while still providing an effective method for preventing VTE. Twenty-six patients stratified as having medium to high risk of VTE who did not receive prophylaxis were identified, generating $154.41 in savings. However, these data should be evaluated with caution since the risks and outcomes associated with not preventing VTE outweigh the economy achieved from not prescribing a drug when a patient needs it. The only case of VTE identified during the study period was related to justified non-adherence to the protocol. CONCLUSION: The protocol is based on scientific evidence that describes an effective therapy to prevent VTE. However, the protocol should be updated because the justifications for non-adherence are based on scientific evidence, and this justified non-adherence generates savings and yields effective disease prevention.

Cost-Effectiveness Evaluation of Heparin Coated Versus Standard Graft for Bypass Surgery in Peripheral Artery Disease Alongside a Randomised Controlled Trial.

OBJECTIVE/BACKGROUND: Heparin coating has recently been shown to reduce the risk of graft failure in arterial revascularisation, at least transiently. The aim of this study was to assess the cost-effectiveness of heparin coated versus standard polytetrafluoroethylene grafts for bypass surgery in peripheral artery disease from a long-term healthcare system perspective. METHODS: Cost-effectiveness evaluation was conducted alongside the Danish part of the Scandinavian Propaten trial in which 431 patients planned for femoro-femoral or femoro-popliteal bypass surgery were randomised to either type of graft and followed for 5 years. Based on the intention to treat principle, the differences in healthcare costs (general practice, prescription medication, hospital admission, rehabilitation, and long-term care in 2015 Euros), life years (LYs), and quality adjusted life years (QALYs) were analysed as arithmetic means with bootstrapped 95% confidence intervals. Cost-effectiveness acceptability curves were used to illustrate the probability of cost-effectiveness for a range of threshold values of willingness to pay (WTP). RESULTS: No statistically significant differences between the randomisation groups were observed for costs or gains of LYs or QALYs. The average cost per QALY was estimated at €10,792. For a WTP threshold of €40,000 per QALY, the overall probability of cost-effectiveness was estimated at 62%, but owing to cost savings in patients with critical ischaemia (cost per QALY <€0), it increased to 89% for this subgroup. CONCLUSION: Until further evidence, heparin coated grafts appear overall, to be cost-effective over standard grafts, but important heterogeneity between claudication and critical ischaemia should be noted. While the optimal choice for claudication remains uncertain, heparin coated grafts should be used for critical ischaemia.

Safety and economic considerations of argatroban use in critically ill patients: a retrospective analysis.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. METHODS: Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS <30), respectively. For calculations, patients (n = 19) without previous history of HIT were compared to patients (n = 23) with a history of HIT before initiation of argatroban. RESULTS: The mean initial argatroban dosage was below 0.4 mcg/kg/min regardless of SAPS score. Maintenance dosage had to be increased in patients with SAPS <30 to 0.54 ± 0.248 mcg/kg/min (p >0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. CONCLUSION: Argatroban can be used at doses < 0.4 mcg/kg/min without an increase in transfusion requirements and at a reduced overall treatment cost compared to heparin.

[Alternatives to heparin and protamine anticoagulation for cardiopulmonary bypass in cardiac surgery]. / Les différentes alternatives d'anticoagulation au couple héparine/protamine en chirurgie cardiaque sous circulation extra-corporelle.

PURPOSE: Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The primary objective of this study was to determine the reliable alternatives for anticoagulation during CPB for cardiac surgery. For each drug proposed, the secondary objectives were to outline the main advantages and disadvantages, to propose a therapeutic protocol, and to provide a cost-benefit analysis. SOURCE: A systematic review of the literature was performed between September 2012 and December 2013. It was based on the protocol established by the "Cochrane collaboration Handbook". Twenty articles were analyzed. The Thériaque database from the University Hospital of Grenoble made the economic analysis possible. PRINCIPAL FINDINGS: Seven alternative anticoagulation strategies were considered: danaparoid sodium, lepirudin, argatroban, bivalirudin, ancrod, idraparinux, and EP217609. Danaparoid sodium has issues with individual variability. Several studies (EVOLUTION-ON, CHOOSE-ON) proposed a reliable therapeutic protocol for bivalirudin. Ancrod resulted in an increase in the transfusion of blood products. Direct thrombin inhibitors offer a promising alternative. EP217609 is a synthetic anticoagulant currently undergoing Phase IIa clinical trials. It is an indirect inhibitor of factor Xa, a direct inhibitor of free and bound thrombin, and can be neutralized by avidin. CONCLUSIONS: The ideal anticoagulation strategy for cardiac surgery with CPB does not exist. Heparin and protamine remain the gold standard for anticoagulation therapy. To date, bivalirudin is the most promising molecule despite its high cost and lack of a readily available antagonist.

Perioperative venous thromboembolism in patients with gynecological malignancies: a lesson from four years of recent clinical experience.

AIM: To analyze clinical characteristics of venous thromboembolisms (VTE) in gynecological malignancies, and to find a cost-effective prophylaxis procedure for post-operative VTE. PATIENTS AND METHODS: We analyzed clinical characteristics of 751 patients who underwent definitive surgery for gynecologic malignancies, and cost-effectiveness of VTE prophylaxis. RESULTS: VTE was diagnosed preoperatively in 4.5% of ovarian cancer cases, more frequently than any other type (p<0.005). Older age and greater length of operation were independent risk factors for postoperative VTE. To prevent eight VTEs in 738 malignant cases, which occurred during day 2 to 10, $617,783, $726,185, or $994,222 were necessary for continuous VTE prophylaxis, using either unfractionated heparin (UFH), low-molecular weight heparin or fondaparinux, respectively. CONCLUSION: A strategy which might be cost-effective for post-surgical management of gynecological malignances is use of UFH three times combined with graduated compression stockings and intermittent pneumatic compression, thorough SpO2 monitoring, and perioperative measurements of the circumference of both sides of thighs and calves.

Is a fully heparin-bonded cardiopulmonary bypass circuit superior to a standard cardiopulmonary bypass circuit?

A best-evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Is a fully heparin bonded cardiopulmonary bypass circuit superior to a standard cardiopulmonary bypass circuit?' Altogether more than 792 papers were found using the reported search, of which 13 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated (Table 1). The studies analysed show that perfusion with heparin-coated and heparin-polymer-coated bypass does not increase the risk of adverse effects but reduces blood loss, re-operation rates, ventilation time, length of intensive care unit (ICU) and hospital stay and is also associated with improved biocompatibility, as evidenced by platelet preservation, reduced leucocyte and complement activation, and proinflammatory cytokine production. The various coated circuits have comparable biocompatibility as evaluated by a range of inflammatory markers and clinical outcomes. Three studies documented a significant decrease in post-operative blood loss (P = 0.001-0.54) and a meta-analysis found that perfusion with a heparin-bonded circuit resulted in a reduction in blood transfusion requirements (20%), ventilation time (P < 0.01), length of time in the ICU (P < 0.01) and also hospital stay (P = 0.02). Two studies found reduced levels of polymorphonuclear elastase (P < 0.018-0.001) and two trials concluded that the use of heparin-coated circuits in combination with low-dose systemic heparin (activated clotting time >250) resulted in the greatest clinical benefit and improvement in inflammation. One study documented significant platelet preservation with the use of third-generation heparin-polymer-bonded circuits (P ≤ 0.05). We conclude that despite heparin-bonded and newer third-generation heparin-polymer-bonded cardiopulmonary bypass circuits having a greater cost per person, their improved clinical outcomes and biocompatibility in patients undergoing cardiac surgery make them a preferable option to standard non-heparin-bonded circuits.

[Economic analysis of dalteparin use in knee surgery at Instituto Mexicano del Seguro Social]. / Análisis económico de dalteparina en la indicacióncirugía de rodilla en el Instituto Mexicano del Seguro Social.

BACKGROUND: Knee surgery is a risk factor for thromboembolic disease. Prophylaxis reduces the risk of this condition. METHODS: Economic and health consequences of drugs preventing and treating thromboembolic disease in patients undergoing knee surgery from the institutional perspective (time horizon: 1 year) were estimated. The measures of effectiveness were: reduction in the number of cases (per 1,000 patients) of deep vein thrombosis, pulmonary embolism, hospital admissions and deaths. Transition probabilities were estimated by meta-analysis. The alternatives were: warfarin (reference), dalteparin, enoxaparin, nadroparin, unfractionated heparin + warfarin, and non-prophylaxis. Data on resources use and costs corresponds to the Instituto Mexicano del Seguro Social (IMSS). Acceptability curves were constructed. RESULTS: No prophylaxis implied three times higher cost ($18,835.10 versus $5,967.10) and less effectiveness in comparison with warfarin. The incremental cost-effectiveness ratios for enoxaparin were $3, $13, $17 and $3 per each additional case of deep vein thrombosis, pulmonary embolism, death and hospital admission avoided. Results of nadroparin and unfractionated heparin were inferior to warfarin (59.1% and 72.9% more costly and less effective in three measures of effectiveness, respectively). Dalteparin showed higher health outcomes and lower cost compared with warfarin (-20.6%). Dalteparin had a higher probability of being cost-effective than enoxaparin. DISCUSSION: thromboprophylaxis is a clinically and economically favorable alternative. The identification of a pharmacoeconomic profile of alternatives to perform it becomes relevant given the increasing pressure on institutional budgets. CONCLUSIONS: Dalteparin would be a cost-saving alternative in thromboprophylaxis of patients undergoing knee surgery at IMSS.

Cost-effectiveness of rivaroxaban versus heparins for prevention of venous thromboembolism after total hip or knee surgery in Sweden.

AIMS: The objective of this study was to evaluate the cost-effectiveness of rivaroxaban versus the low-molecular-weight heparins (LMWH) enoxaparin and dalteparin for the prevention of venous thromboembolism (VTE) after total hip replacement and total knee replacement in Sweden. METHODS: The model included acute venous thromboembolic events and long-term complications over a 5-year time horizon represented by an acute and a chronic phase with 1-year cycles. Transition probabilities were derived from the Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) clinical trials. RESULTS: In patients undergoing total hip replacement, the incremental cost per additional quality-adjusted life-year of extended prophylaxis for 35 days with rivaroxaban versus 14 days of prophylaxis with enoxaparin or dalteparin was SEK29,400 and SEK35,400, respectively. In total knee replacement patients, 14 days of rivaroxaban dominated 14 days of LMWH as prophylaxis for VTE. CONCLUSION: The results of the economic model consistently showed that, over a 5-year period, rivaroxaban is a cost-effective alternative to 14 days of LMWH for VTE prophylaxis in Sweden.

Economic impact of switching to bivalirudin for a primary percutaneous coronary intervention in a US hospital.

BACKGROUND: The addition of glycoprotein IIb/IIIa inhibitors (GPIs) to heparin in percutaneous coronary intervention (PCI) procedures has been demonstrated to reduce ischemic complications; however, GPI use is known to increase the risk of bleeding events, which are linked to increased mortality, longer hospital length of stay, greater medical resource utilization, and increased costs. New antithrombotic therapies have the potential to improve clinical outcomes and decrease costs. The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study of bivalirudin demonstrated significantly reduced clinical event rates (mortality and bleeding) compared with an unfractionated heparin (UFH)+GPI regimen. OBJECTIVE: The potential clinical and economic value of implementing a bivalirudin-based strategy for ST-segment elevation myocardial infarction (STEMI) patients receiving primary PCI (PPCI) is compared with current UFH+GPI-based practice from a US hospital perspective. METHODS: A budget impact model was developed to compare treatment of STEMI patients undergoing PPCI with a bivalirudin- or UFH+GPI-based strategy. Clinical data for the model were derived from the HORIZONS-AMI trial, and included 30-day event rates for major complications (eg, protocol bleeding, Q-wave MI, repeat PCI, and coronary artery bypass graft procedures). United States cost data and clinical practice data were derived from a Premier Perspective™ database analysis and published sources. RESULTS: Overall, average procedure costs per UFH+GPI-treated patient were $18,561. Treating patients with bivalirudin (incorporating 7.2% provisional GPI use per HORIZONS-AMI) may save $1690 per patient (average procedural cost, $16,872). In extrapolating these benefits to the American College of Cardiology/American Heart Association recommended institutional minimum of 36 PPCIs annually, 1 major bleeding event (3.7%) and 3 minor bleeding events (6.8%) could be averted with use of bivalirudin. In addition, introducing a bivalirudin-based strategy to treat a minimum cohort of 36 STEMI patients would save the hospital budget $60,807 (9%) per year. CONCLUSION: Using a bivalirudin-based strategy in STEMI patients undergoing PPCI is associated with favorable clinical and economic outcomes when compared with an UFH+GPI-based strategy in a US hospital setting.

Heparin dose response is independent of preoperative antithrombin activity in patients undergoing coronary artery bypass graft surgery using low heparin concentrations.

BACKGROUND: Unfractionated heparin's primary mechanism of action is to enhance the enzymatic activity of antithrombin (AT). We hypothesized that there would be a direct association between preoperative AT activity and both heparin dose response (HDR) and heparin sensitivity index (HSI) in patients undergoing coronary artery bypass graft surgery. METHODS: Demographic and perioperative data were collected from 304 patients undergoing primary coronary artery bypass graft surgery. AT activity was measured after induction of general anesthesia using a colorimetric method (Siemens Healthcare Diagnostics, Tarrytown, NY). Activated coagulation time (ACT), HDR, and HSI were measured using the Hepcon HMS Plus system (Medtronic, Minneapolis, MN). Heparin dose was calculated for a target ACT using measured HDR by the same system. Multivariate linear regression was performed to identify independent predictors of HDR. Subgroup analysis of patients with low AT activity (<80% normal; <0.813 U/mL) who may be at risk for heparin resistance was also performed. RESULTS: Mean baseline ACT was 135 ± 18 seconds. Mean calculated HDR was 98 ± 21 s/U/mL. Mean baseline AT activity was 0.93 ± 0.13 U/mL. Baseline AT activity was not significantly associated with baseline or postheparin ACT, HDR, or HSI. Addition of AT activity to multivariable linear regression models of both HDR and HSI did not significantly improve model performance. Subgroup analysis of 49 patients with baseline AT <80% of normal levels did not reveal a relationship between low AT activity and HDR or HSI. Preoperative AT activity, HDR, and HSI were not associated with cardiac troponin I levels on the first postoperative day, intensive care unit duration, or hospital length of stay. CONCLUSION: Although enhancing AT activity is the primary mechanism by which heparin facilitates cardiopulmonary bypass anticoagulation, low preoperative AT activity is not associated with impaired response to heparin or to clinical outcomes when using target ACTs of 300 to 350 seconds.

The potential benefits of low-molecular-weight heparins in cancer patients.

Cancer patients are at increased risk of venous thromboembolism due to a range of factors directly related to their disease and its treatment. Given the high incidence of post-surgical venous thromboembolism in cancer patients and the poor outcomes associated with its development, thromboprophylaxis is warranted. A number of evidence-based guidelines delineate anticoagulation regimens for venous thromboembolism treatment, primary and secondary prophylaxis, and long-term anticoagulation in cancer patients. However, many give equal weight to several different drugs and do not make specific recommendations regarding duration of therapy. In terms of their efficacy and safety profiles, practicality of use, and cost-effectiveness the low-molecular-weight heparins are at least comparable to, and offer several advantages over, other available antithrombotics in cancer patients. In addition, data are emerging that the antithrombotics, and particularly low-molecular-weight heparins, may exert an antitumor effect which could contribute to improved survival in cancer patients when given for long-term prophylaxis. Such findings reinforce the importance of thromboprophylaxis with low-molecular-weight heparin in cancer patients.

Chronically anticoagulated patients who need surgery: can low-molecular-weight heparins really be used to "bridge" patients instead of intravenous unfractionated heparin?

Patients at high risk of arterial or venous thromboembolic events often receive chronic treatment with long-term oral anticoagulants such as warfarin. However, if these patients require an invasive procedure, they may require a temporary interruption of their warfarin therapy to minimize their bleeding risk during the procedure. As warfarin has a long half-life and an unpredictable pharmacokinetic profile, short-acting parenteral anticoagulants, such as unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH), may be of benefit in protecting the patient from thromboemboli while their warfarin dose is withheld. Such "bridging therapy" has traditionally been provided in-hospital with intravenous UFH; however, recent data have suggested that LMWH may be an effective alternative, with potential cost-savings due to the ability to provide bridging therapy in the outpatient setting.

Economic evaluation of bivalirudin with or without glycoprotein IIb/IIIa inhibition versus heparin with routine glycoprotein IIb/IIIa inhibition for early invasive management of acute coronary syndromes.

OBJECTIVES: The aim of this study was to determine the economic impact of several anticoagulation strategies for moderate- and high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients managed invasively. BACKGROUND: The ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial demonstrated that bivalirudin monotherapy yields similar rates of ischemic complications and less bleeding than regimens incorporating glycoprotein IIb/IIIa receptor inhibitors (GPI) for moderate- and high-risk NSTE-ACS. METHODS: In ACUITY, 7,851 U.S. patients were randomized to: 1) heparin (unfractionated or enoxaparin) + GPI; 2) bivalirudin + GPI; or 3) bivalirudin monotherapy. Patients assigned to GPI were also randomized to upstream GPI before catheterization or selective GPI only with percutaneous coronary intervention. Resource use data were collected prospectively through 30-day follow-up. Costs were estimated with standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. RESULTS: At 30 days, ischemic events were similar for all groups. Major bleeding was reduced with bivalirudin monotherapy compared with heparin + GPI or bivalirudin + GPI (p < 0.001). Length of stay was lowest with bivalirudin monotherapy or bivalirudin + catheterization laboratory GPI (p = 0.02). Despite higher drug costs, aggregate hospital stay costs were lowest with bivalirudin monotherapy (mean difference range: $184 to $1,081, p < 0.001 for overall comparison) and at 30 days (mean difference range: $123 to $938, p = 0.005). Regression modeling demonstrated that hospital savings were primarily due to less major and minor bleeding with bivalirudin ($8,658/event and $2,282/event, respectively). CONCLUSIONS: Among U.S. patients in the ACUITY trial, bivalirudin monotherapy compared with heparin + GPI resulted in similar protection from ischemic events, reduced bleeding, and shorter length of stay. Despite higher drug costs, aggregate hospital and 30-day costs were lowest with bivalirudin monotherapy. Thus bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate- and high-risk NSTE-ACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Clinical factors influencing the sensitivity to warfarin when restarted after surgery.

BACKGROUND AND OBJECTIVE: Resumption of oral anticoagulation after surgery may result in a different maintenance dose of warfarin than before the procedure. Knowledge of the clinical determinants of postoperative response could help avoid excessive anticoagulation in sensitive patients or avoid extended delays in achieving a therapeutic level in resistant patients. DESIGN: Retrospective review. SUBJECTS: Two hundred warfarin-treated patients who were managed by our clinic for surgery. OUTCOME: Two independent adjudicators classified the postoperative response to warfarin as Resistant, Normal or Sensitive, based on previous maintenance dose, international normalized ratio (INR) on the day of resumption, number of days until INR of >1.9 and doses of warfarin given. A third adjudicator resolved disagreements. Clinical data were extracted from the patient records and correlated with the response. RESULTS: Interobserver agreement for classification of postoperative response was moderate (weighted kappa 0.46) with 37 (18.5%) considered resistant, 135 (67.5%) normal, 27 (13.5%) sensitive and one patient was not classifiable. The main type of surgery was cardiac. In univariable analysis only addition of amiodarone after surgery was associated with a sensitive response (P = 0.04). After adjustment for all other factors with an ordered categorical response, amiodarone remained as the sole independent risk factor (P = 0.02) for a sensitive response, odds ratio 0.41 (95% confidence interval 0.19-0.89) for Normal instead of Sensitive or for Resistant instead of Normal. CONCLUSION: Altered sensitivity to warfarin occurs in about one-third of patients after surgery and can be predicted by the introduction of concomitant amiodarone therapy but not by patient factors or the nature of the procedure. Changes in concomitant medications after surgery should alert doctors of the potential for increased sensitivity to warfarin.

Cost-effectiveness of dalteparin versus unfractionated heparin as venous thromboembolism prophylaxis in malignant gynecologic surgery.

Venous thromboembolic events (VTEs) are serious complications that may occur in the patient undergoing surgery for gynecologic malignancies. The American College of Chest Physicians recommends unfractionated heparin or low-molecular weight heparin as prophylaxis for deep vein thrombosis and pulmonary embolism in this patient population. Cost-effectiveness analyses comparing unfractionated heparin 3 times a day versus once daily dalteparin using published efficacy and safety data demonstrate cost savings if dalteparin were routinely utilized as VTE prophylaxis. Sensitivity analyses support this finding at the upper end of the range of reported proximal DVT, nonfatal pulmonary embolism, and major bleeding incidences. These findings should be viewed as preliminary, and institutions are encouraged to perform their own cost-effectiveness studies in this patient population.

Comparison of cost, effectiveness, and safety of injectable anticoagulants used for thromboprophylaxis after orthopedic surgery.

PURPOSE: The cost, effectiveness, and safety of injectable anticoagulants used for thromboprophylaxis after orthopedic surgery were compared. METHODS: This retrospective, observational, cross-sectional, cohort analysis of inpatient billing data was conducted from the institutional perspective. Patients who received dalteparin, enoxaparin, fondaparinux, or unfractionated heparin after orthopedic surgery were included in the analysis. The primary outcome measure was the mean aggregated cost per patient treated with each injectable anticoagulant. Secondary outcomes included the percentages of patients in each treatment group who had a venous thromboembolism (VTE) or major bleeding episode. RESULTS: Mean total adjusted costs were significantly lower for fondaparinux ($18,019) compared with other anticoagulants, with unfractionated heparin being the most costly ($20,835). Relative adjusted cost differences were 1.4% (p = 0.0127), 1.8% ( p = 0.0105), and 14.6% (p < 0.0001) higher for enoxaparin, dalteparin, and unfractionated heparin, respectively, compared with fondaparinux. Significantly fewer fondaparinux-treated patients had a VTE event compared with the other treatment groups. The use of dalteparin was associated with fewer major bleeding events, and no significant differences in the rate of major bleeding events were observed among groups treated with fondaparinux, enoxaparin, or unfractionated heparin. CONCLUSION: A retrospective analysis of inpatient billing data showed that, among orthopedic surgery patients, fondaparinux was associated with lower institutional cost and a lower frequency of VTE than were dalteparin, enoxaparin, and unfractionated heparin. Dalteparin was associated with a lower rate of major bleeding events than was fondaparinux, but there were no significant differences in such events among fondaparinux, enoxaparin, and unfractionated heparin.