Economic evaluation of outpatient treatment with low-molecular-weight heparin for proximal vein thrombosis.

BACKGROUND: The safety and efficacy of taking low-molecular-weight heparin at home was previously demonstrated in a clinical trial in which patients with acute proximal deep vein thrombosis were randomized to receive either intravenous standard heparin in the hospital or subcutaneous low-molecular-weight heparin administered primarily at home. Treatment in the home has the potential to substantially reduce the cost to the health care system. METHODS: To conduct an economic evaluation we prospectively collected data on resource use and health-related quality of life (Medical Outcomes Study Short-Form 36) on the 300 patients who formed the trial stratum presenting with proximal vein thrombosis as outpatients, of whom 151 received standard heparin and 149 received low-molecular-weight heparin. The primary viewpoint of the analysis was societal, and costs included health care costs, patient travel costs, and productivity costs as a result of time off work. Costs were assessed over a period of 3 months from randomization. Quality of life was assessed as the change in Short-Form 36 domain scores from baseline to day 7 for each treatment group. All costs are reported in 1997 Canadian dollars. RESULTS: There were 11 recurrent thromboembolic events and 1 bleed in the 151 patients who received standard heparin; the corresponding data for the 149 patients receiving low-molecular-weight heparin were 10 and 4, respectively. The mean cost per patient who received standard heparin was Can $5323 compared with Can $2278 for low-molecular-weight heparin, a total societal cost savings per patient using low-molecular-weight heparin of Can $3045 (95% confidence interval, Can $2012-$4050). There was no difference in quality of life between the 2 groups except for the domain of social functioning, where a greater improvement from baseline to day 7 was observed for the low-molecular-weight heparin group vs the standard heparin group (P =.005). CONCLUSIONS: For patients with acute proximal deep vein thrombosis, treatment at home with low-molecular-weight heparin is less costly than hospital-based treatment with standard heparin. The economic evidence in favor of outpatient treatment with low-molecular-weight heparin exhibits dominance; a situation of reduced cost is created with no compromise in clinical outcomes or patients' quality of life.     

Cost comparison of at-home treatment of deep venous thrombosis with low molecular weight heparin to inpatient treatment with unfractionated heparin

Abstract
Aims : Low molecular weight heparins (LMWH) permit safe and effective treatment of uncomplicated deep venous thrombosis (DVT) at home. The aim of this study was to evaluate the cost minimization, cost shifting and patient satisfaction associated with at-home DVT treatment using the LMWH enoxaparin, compared to standard inpatient care in an Australian health-care setting.
Methods : Subjects presenting with a principal diagnosis of uncomplicated DVT to the Emergency Department at The Queen Elizabeth Hospital, Adelaide, were recruited over 1997–1999. Costs to the hospital, to Federal funding (Medicare) and to patients were tracked prospectively, and satisfaction was also measured. Subjects were matched to historical controls (1994–1997) for age, gender and level of comorbidity (same or lower) by two medical officers who were blinded to costs. Control costs were obtained using the clinical costing system Trendstar®, and adjusted for consumer price index.
Results : Twenty-eight subjects participated in the at-home programme. Of these, 26 were discharged without any inpatient admission (including one who agreed to self-injection) and two were admitted briefly. Audit demonstrated that only 29% of eligible subjects were managed at home. Mean (SEM) total treatment cost was $756 (76) per patient for at-home, and $2208 (146) for controls. Minimal cost shifts to patients and to Medicare occurred, and satisfaction was high.
Conclusions : At-home treatment of uncomplicated DVT using enoxaparin in an Australian metropolitan setting provides effective cost minimization, with little cost-shifting. Our cost minimisation estimates are conservative as most at-home subjects received enoxaparin twice daily (now used once per day) and controls had at least as high comorbidity. However, uptake of the at-home programme was limited. (Intern Med J 2002; 32: 29–34)     

Management of proximal deep vein thrombosis

Iliofemoral DVT constitutes approximately 20-25% of lower limb DVT and represents a specific subgroup of patients at highest risk for post-thrombotic syndrome (PTS). Anticoagulation alone has no significant thrombolytic activity and has not impact on PTS prevention. Early thrombus removal has reduced PTS in uncontrolled reports and reviews but major trials are awaited. The optimal timing for treatment appear to be thrombus <2 weeks old and, methods for thrombus removal include direct open or suction thrombectomy, catheter directed thrombolysis (CDT), with or without percutaneous mechanical thrombectomy (PMT) devices. Three principle types of PMT device are in use (rotational, rheolytic and ultrasound enhanced devices) and are combined with CDT in pharmocomechanical thrombolysis (PhMT) to enhance early thrombus removal. These devices have individual device specific attributes and side effects that are additional to the bleeding complications of thrombolysis. A number of additional interventions may be utilised to the improve results of CDT and PhMT. IVC filter deployment to reduce periprocedural PE, is supported by little evidence unless an indication for its use already exists. However, balloon venoplasty and vein stents undoubtedly vein patency after treatment. Early thrombus removal comes with additional upfront costs derived from devices, imaging and critical care bed usage. However, significant potential savings from reduction in PTS and rethrombosis rates may reduce overall societal costs. This review focuses on iliofemoral thrombosis, however, the less commonly encountered but clinically important subclavian vein thrombosis is also discussed.     

Cost-effectiveness of low-molecular-weight heparin in the treatment of proximal deep vein thrombosis

OBJECTIVE: To estimate the cost-effectiveness of low-molecular-weight heparin (LMWH) in the treatment of proximal lower extremity deep venous thrombosis. DESIGN: Cost-effectiveness analysis that includes the treatment of the index case and simulated 3-month follow-up. SETTING: Acute care facility. PATIENTS AND PARTICIPANTS: Hypothetical cohorts of 1,000 patients who present with proximal deep venous thrombosis. INTERVENTIONS: Intravenous unfractionated heparin (UH), LMWH (40% at home, 60% in hospital), or selective UH/LMWH (UH for hospitalized patients and LMWH for patients treated at home). MEASUREMENTS AND MAIN RESULTS: The outcomes were recurrent thrombosis, mortality, direct medical costs, and marginal cost-effectiveness ratios from the payer’s perspective. At the base-case and under most assumptions in the sensitivity analysis, the LMWH and the selective UH/LMWH strategies dominate the UH strategy i.e., they result in fewer cases of recurrent thrombosis and fewer deaths, and they save resources. The savings occur primarily by decreasing the length of stay. The LMWH strategy resulted in lower costs as compared with the UH strategy when the proportion of patients treated at home was more than 14%. Treating 1,000 patients with the LMWH strategy as compared with the UH/LMWH strategy would result in 10 fewer cases of recurrent thrombosis, 1.2 fewer deaths, at an additional cost of $96,822; the cost-effectiveness ratio was $9,667 and $80,685 per recurrent thrombosis or death prevented, respectively. CONCLUSIONS: Treatment with LMWH leads to savings and better outcomes as compared with UH in patients with lower extremity deep venous thrombosis. The selective UH/LMWH strategy is an alternative option. Presented in part at the 20th annual meeting, Society of General Internal Medicine, Washington, DC, May 1–3, 1997.     

Cost for inpatient care of venous thrombosis: a trial of enoxaparin vs standard heparin

BACKGROUND: Enoxaparin, a low-molecular-weight heparin administered to hospitalized patients once or twice daily, has shown efficacy and safety equivalent to unfractionated heparin in the treatment of acute venous thromboembolic disease. Although the cost of either enoxaparin regimen is greater than that of unfractionated heparin, the overall cost of care for each of these 3 treatment strategies is unknown. METHODS: A cost minimization analysis of a 3-month, partially blinded, randomized, controlled efficacy and safety trial of anticoagulant therapy for deep vein thrombosis. Three hundred thirty-nine hospitalized patients with symptomatic lower extremity deep vein thrombosis were randomly assigned to initial therapy with subcutaneous enoxaparin either once (n = 112) or twice (n = 123) daily, or with dose-adjusted intravenous unfractionated heparin (n = 104), followed by long-term oral anticoagulant therapy. Estimated 1997 total cost from a third-party payer perspective for the 3-month episode of care was calculated by assigning standard unit costs to counts of medical resources used by each patient in the clinical trial. RESULTS: Average total cost for the 3-month episode of care was similar across all 3 treatment regimens: once-daily dose of enoxaparin, $12,166 (95% confidence interval [CI], $10,744-$13,588); twice-daily dose of enoxaparin, $11,558 (95% CI, $10,201-$12,915); and unfractionated heparin, $12,146 (95% CI, $10,670-$12,622). Bootstrapped estimates and sensitivity analyses did not significantly change findings. CONCLUSIONS: There was no significant difference in the overall cost for the 3-month episode of care for patients treated with either enoxaparin or unfractionated heparin. Additional acquisition costs for anticoagulant medication among patients treated with enoxaparin were offset by savings associated with lower incidence of hospital readmission and shorter duration of venous thromboembolism-related readmissions.     

Clinical outcome and cost of hospital vs home treatment of proximal deep vein thrombosis with a low-molecular-weight heparin: the Vascular Midi-Pyrenees study

BACKGROUND: Low-molecular-weight heparins have been shown to be effective and safe in the treatment of deep vein thrombosis. To our knowledge, there have been no direct comparisons of such treatment on an outpatient vs an inpatient basis. OBJECTIVE: To conduct a randomized, comparative, multicenter trial to evaluate the clinical outcomes and treatment costs of deep vein thrombosis in the outpatient and inpatient settings. METHODS: Two hundred one patients presenting with proximal deep vein thrombosis, without known risk factors for pulmonary embolism or hemorrhagic complications, were randomized to receive a low-molecular-weight heparin at the registered dose followed by an oral anticoagulant for up to 6 months, either in the hospital for the first 10 days followed by treatment at home (n=102) or at home from the outset (n=99). The primary clinical outcome was the incidence of venous thromboembolism recurrence, pulmonary embolism, or major bleeding. The economic analysis was performed from the point of view of the health insurance company. Total costs of the 2 management strategies were calculated to compare the cost consequences during the first 10 days. RESULTS: No differences in clinical outcome were detectable between the 2 groups. There was no increase in the rates of primary efficacy outcome in the patients treated at home vs in the hospital (3.0% vs 3.9%), while a cost reduction of 56% was demonstrated for outpatient management. CONCLUSION: For patients with proximal deep vein thrombosis and no symptoms of pulmonary embolism or increased risk of major bleeding, home treatment using a low-molecular-weight heparin is an effective, safe, and cost-saving strategy.     

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A cost-effectiveness analysis.

BACKGROUND: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed. OBJECTIVE: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. DESIGN: Decision model. DATA SOURCES: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources. TARGET POPULATION: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An in-patient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin. RESULTS OF BASE-CASE ANALYSIS: Total costs for inpatient treatment were $26,516 for low-molecular-weight heparin and $26,361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home. RESULTS OF SENSITIVITY ANALYSIS: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75,000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge. CONCLUSIONS: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management.     

The treatment of deep venous thrombosis. Thrombolysis vs heparin

Acute and subacute deep venous thrombosis can be followed by two serious complications: pulmonary embolism feared in the early stadium and the postthrombotic syndrome (PTS) as a late complication. After a lapse of months and years there might appear a complete or incomplete recanalization, but the valves of the veins will be destroyed. Therefore it is understandable to strive first an active therapy as thrombectomy or thrombolysis to remove thrombosis. There will be released a physiological tissue plasminogen activator from the endothelium of the vein increasing a local fibrinolytic activity. But it is not strong enough to reopen the occlusion within a few days. This is only possible adding exogenous activators as streptokinase, urokinase and recently rt-PA. Heparin is well known at low-dose subcutaneously for thrombosis prophylaxis. The high doses of heparin infusion intravenously with 30-40,000 units daily are used "therapeutically" inhibiting growth-promotion of the thrombus and reducing the incidence of pulmonary embolism markedly. In respect of a postthrombotic syndrome (oedema, leg ulcers) it needs the evaluation of the early and follow up late results and the analysis of efficiency and risk of the two models of treatment. It was necessary comparing the success rate of reopening of the occluded veins after some days and follow up 5 or 6 years in clinical studies. The reopening rate in thrombolysis was about 3 times higher than in heparin therapy. But in contrast bleeding was 3 times lower in heparin therapy. For the long term follow up, physical examination, doppler-sonography phlebodynamometry and vein occlusion plethysmography were assessed. The acute intervention, regarding treatment, turned out to be the crucial prognostic parameter. Syndromes and clinical findings did indeed correlate quite well with the outcome of fibrinolytic treatment. Postthrombotic syndrome was rare in cases with complete patency. In cases where patency was only partially or not at all achieved, postthrombotic syndrome was present to a higher degree the more central and the more extensive the remaining thrombus was. In deep venous thrombosis of the lower extremity thrombolytic therapy is recommended mostly to younger patients with acute, the popliteal and the femoral vein including thrombosis, except of contraindications. More over in each of an individual case it has to be decided whether the aggressive or conservative therapy is to prefer.     

Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin

OBJECTIVES: To compare the rates of bleeding complications in patients with renal insufficiency who receive anticoagulation therapy with the full therapeutic dose, unfractionated heparin (UFH), or with twice-daily enoxaparin. SETTING: A 325-bed community teaching hospital. STUDY TYPE: Retrospective cohort study. METHODS: The medical records of all patients with renal insufficiency who received anticoagulation therapy with UFH or enoxaparin during a 13-month period were reviewed for the occurrence of major and minor bleeding. Incidence rates were computed per 1,000-person days of anticoagulation therapy. Comparisons were made across categories of renal insufficiency and other potential confounders. RESULTS: A total of 620 patients with estimated glomerular filtration rates of < 60 mL/min were studied. Of these, 331 received anticoagulation therapy with UFH, 250 with enoxaparin, and 39 with both (not simultaneously). The major bleeding rates were 26.3 per 1,000 person-days for UFH and 20.7 per 1,000 person-days for enoxaparin. Major bleeding complications were similarly increased for both UFH and enoxaparin therapy across categories of worsening renal insufficiency. Patients with severe renal insufficiency while receiving enoxaparin had a 154% excess incidence of minor bleeding compared to those receiving UFH (incidence ratio, 2.54; 95% confidence interval, 1.01 to 6.36). Worsening renal insufficiency, female gender, and prolonged duration of anticoagulation therapy emerged as the main determinants for bleeding complications. CONCLUSION: Both the twice-daily enoxaparin and UFH regimens are associated with comparable increases in major bleeding complications in patients with renal dysfunction receiving full-dose anticoagulation therapy. Both agents should be used with caution in anticoagulation therapy for patients with renal insufficiency.     

Incidence and clinical relevance of heparin-induced antibodies in patients with deep vein thrombosis treated with unfractionated or low-molecular-weight heparin

The frequency of heparin-induced thrombocytopenia (HIT) varies between different clinical treatment settings and remains unknown for patients treated with unfractionated (UFH) or low-molecular-weight heparin (LMWH) because of deep vein thrombosis. In this multicentre, open-label study, 1137 patients with deep vein thrombosis were randomly assigned to UFH for 5-7 d, reviparin, a LMWH, for 5-7 d (short-treated group) or reviparin for 28 d (long-treated group). Heparin-platelet factor 4 antibodies (HPF4-A) were determined on d 5-7 and d 21. Heparin-induced thrombocytopenia was defined by clinical evaluation. Two patients in the UFH group (incidence: 0.53%, 95% confidence interval (CI): 0.06-1.91) and two patients in the long-treated LMWH group (incidence: 0.53%, 95% CI: 0.06-1.92) had HIT, while no HIT was observed in the short-treated LMWH group. Pulmonary embolism developed in one of the HIT-patients, who had HPF4-A and was treated with UFH. On d 5-7 the incidence of HPF4-A was 9.1% in the UFH group, 2.8% in the short-treated LMWH group and 3.7% in the long-treated LMWH group, with a significant increase to 20.7% in the UFH group and to 7.5% in the long-treated LMWH group on d 21. Therefore the incidence of HPF4-A and heparin-induced thrombocytopenia was lower in patients treated with LMWH compared with UFH for the same duration of treatment.     

Non-ST elevation acute coronary syndrome: changes of parameters of hemostasis during and after treatment with unfractionated heparin and enoxaparin

AIM: To compare changes of parameters of hemostasis in patients with non-ST elevation acute coronary syndrome (NSTEACS) during and after treatment with unfractionated heparin (UFH) and low molecular weight heparin (LMWH) enoxaparin. MATERIAL: Control groups of 2 randomized studies of effects of thienopyridines in NSTEACS with similar inclusion criteria. METHODS: In patients (n=18) of study one UFH was infused intravenously for 54.2+/-22.3 h, in patients of study two subcutaneous enoxaparin 1 mg/kg b.i.d. was used for 76.2+/-28.3 h. Levels of D-dimer (DD), thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), von Willebrand factor (vWF), fibrinogen, tissue plasminogen activator (TPA) and activity of its inhibitor (PAI), soon after start of treatment with heparins and in 1, 3, 7 and 14 days. RESULTS AND CONCLUSION: Short term lowering of DD and TAT levels occurred during UFH infusion apparently reflecting primary antithrombin action of UFH. During LMWH use DD level remained unchanged however its lowering was observed after cessation of LMWH (on days 7 and 14). The use of LMWH was not associated with increases of thrombinemia (TAT), thrombin generation (F1+2), and fibrinogen which were registered after end of UFH infusion (days 3, 7 and 14). Neither UFH nor LMWH prevented acute phase vWF elevation. The use of both heparins was associated with changes that could be interpreted as profibrinolytic. In LMWH treated patients these changes (elevations of TPA level) became manifested early (on day 3) and were short lived while in UFH treated patients they appeared later (on day 7) and were prolonged (as lowered PAI activity on day 14).     

Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin.

OBJECTIVE: To determine the relative efficacy and safety of low molecular weight (LMW) heparin (Enoxaparin) compared with standard calcium heparin for the prevention of postoperative deep vein thrombosis in patients undergoing elective hip surgery. DESIGN: A double-blind, randomized, controlled trial. PATIENTS: Six hundred sixty-five consecutive patients undergoing hip replacement at five participating hospitals. INTERVENTIONS: Patients received either fixed-dose LMW heparin, 30 mg subcutaneously twice daily, or fixed-dose standard calcium heparin, 7500 units subcutaneously twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge if sooner. MEASUREMENTS: All patients had postoperative I-125-fibrinogen leg scanning and impedance plethysmography. If results of one or both tests were positive, then venography was done. Otherwise, venography was done between day 10 and day 14, or sooner if the patient was ready for discharge. RESULTS: Evaluable venograms were obtained in 258 of the 333 patients randomly assigned to receive LMW heparin and in 263 of the 332 patients assigned to receive calcium heparin. For patients with evaluable venograms, thrombosis was detected in 50 patients (19.4%) who received LMW heparin compared with 61 patients (23.2%) who received standard heparin (difference, -3.8%; 95% CI, -11.1% to 3.6%) (P greater than 0.2). Proximal deep vein thrombosis was detected in 5.4% of the patients receiving LMW heparin and in 6.5% of the patients receiving standard heparin (difference, -1.1%; CI, - 5.2% to 3.3%) (P greater than 0.2). For the entire group of 665 patients, venous thrombosis occurred in 17.1% given LMW heparin and in 19.0% given standard heparin. Hemorrhagic complications occurred in 31 patients (9.3%) given standard heparin and in 17 patients (5.1%) given LMW heparin (difference, 4.2%; CI, 0.3% to 8.2%) (P = 0.035). The relative risk reduction was 45%. The rate of major bleeding in the standard heparin group was 5.7% compared with 3.3% in the LMW heparin group (difference, 2.4%; CI, -1.0% to 5.4%) (P = 0.13). The relative risk reduction was 42%. CONCLUSION: Low molecular weight heparin is significantly less hemorrhagic than standard unfractionated heparin; the difference in the rate of deep vein thrombosis, although not statistically significant (P greater than 0.2), favors the use of LMW heparin.     

Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction.

AIMS: To compare the efficacy and safety of low molecular weight heparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. METHODS AND RESULTS: Three-hundred patients receiving fibrinolytic therapy following acute myocardial infarction were randomly assigned to low molecular weight heparin as enoxaparin (40 mg intravenous bolus, then 40 mg subcutaneously every 8 h, n=149) or unfractionated heparin (5000 U intravenous bolus, then 30 000 U. 24 h(-1), adjusted to an activated partial thromboplastin time 2-2.5x normal, n=151) for 4 days in conjunction with routine therapy. Clinical and therapeutic variables were analysed, in addition to use of enoxaparin or unfractionated heparin, to determine independent predictors of the 90-day composite triple end-point (death, non-fatal reinfarction, or readmission with unstable angina). The triple end-point occurred more frequently in patients receiving unfractionated heparin rather than enoxaparin (36% vs. 26%; P=0.04). Logistic regression modelling of baseline and clinical variables identified the only independent risk factors for recurrent events as left ventricular failure, hypertension, and use of unfractionated heparin rather than enoxaparin. There was no difference in major haemorrhage between those receiving enoxaparin (3%) and unfractionated heparin (4%). CONCLUSION: Use of enoxaparin compared with unfractionated heparin in patients receiving fibrinolytic therapy for acute myocardial infarction was associated with fewer recurrent cardiac events at 90 days. This benefit was independent of other important clinical and therapeutic factors.     

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.

BACKGROUND: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin. PURPOSE: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis. DATA SOURCES: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies. STUDY SELECTION: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis. DATA EXTRACTION: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument. DATA SYNTHESIS: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, -0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2). CONCLUSIONS: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences.     

Effect of thrombocytopenia on outcomes following treatment with either enoxaparin or unfractionated heparin in patients presenting with acute coronary syndromes

Thrombocytopenia is associated with an increased risk for adverse cardiac events and bleeding in patients presenting with acute coronary syndromes (ACS) treated with unfractionated heparin (UFH). Enoxaparin has been shown to improve outcomes in ACS; however, its effect on the development of thrombocytopenia in this population is not well documented. This study was conducted to examine the incidence and clinical importance of thrombocytopenia in patients presenting with non-ST-elevation ACS randomized to treatment with enoxaparin or UFH. Thrombocytopenia was defined as a platelet count <100 x 10(9)/L or a >50% decrease from baseline. Thrombocytopenia developed in a total of 93 of 3,910 patients during the follow-up period of 14 days; the incidence was similar between study arms. The development of thrombocytopenia was associated with more frequent death, nonfatal myocardial infarction, and urgent revascularization during the study period (odds ratio 2.96, p = 0.001). This association was independent of assignment to treatment with enoxaparin or UFH (p for interaction = 0.47). Major bleeding was also more common in patients with thrombocytopenia regardless of treatment. In conclusion, thrombocytopenia is a significant correlate of adverse events in patients presenting with non-ST-elevation ACS treated with either enoxaparin or UFH.