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A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention. Results of the Evaluating Enoxaparin Clotting Times (ELECT) Study.

OBJECTIVES: The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND: In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS: We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS: The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every approximately 30-s rise. CONCLUSIONS: Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal.

Angioplasty, Balloon, Coronary↗

[Decrease of total hemorrhage with reduced doses of enoxaparin in high risk unstable angina. ENHNFAI study. (Enoxaparin vs non-fractionated heparin in unstable angina). Preliminary report].

UNLABELLED: In this prospective, randomized and controlled study, we compare complications in 2 groups of patients: group 1, enoxaparin 0.8 mg/kg, subcutaneous every 12 hours during 5 days, and group 2, intravenous unfractionated heparin during 5 days, by infusion treated to activate partial tromboplastin time 1.5-2 the upper limit of normal. Blood samples were obtained at 4, 12, 24 hours and at day 5 of treatment, to measure anti-Xa levels, and also, evaluated end points at 30 days, between groups. Univariate and multivariate logistic regression analyses were performed with clinical and angiographic variables between groups, with p < 0.05. RESULTS: 203 consecutive patients, average age of 60.5 +/- 11.2 years, and 80% men, were included. There were no differences in clinical and angiographic characteristics. All patients with enoxaparin had therapeutic levels of anti-Xa, of 0.5 to 0.67 U/mL. There was increasing risk of total bleeding in group 2 (18.7%) than in group 1 (5.6%), with RR = 1.72 (95% CI 1.29, 2.29), p = .003. Also, there was 33.3% of MACE in group 2, and only 17.8% in group 1, with RR = 1.88 (CI 95% 1.29, 2.29), p = .011. CONCLUSIONS: 1) Low doses of enoxaparine achieve therapeutic levels, since the first 4 hours of treatment. 2) A significant reduction of total bleeding occurred with the low doses of enoxaparin, with the same efficacy to reduce MACE during follow-up.

Aged↗

Enoxaparin for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery: findings of the prophylaxis against VTE outcomes in bariatric surgery patients receiving enoxaparin (PROBE) study.

BACKGROUND: Obese patients undergoing bariatric surgery are at significant risk for venous thromboembolism (VTE). We performed a multicenter, retrospective survey to evaluate the safety and efficacy of enoxaparin for thromboprophylaxis in patients with morbid obesity undergoing primary bariatric surgery. METHODS: From January to December 2002, 668 patients who underwent primary bariatric surgery at 5 centers were analyzed retrospectively. Baseline patient demographics, objectively diagnosed cases of VTE, and bleeding events were recorded. Patients received enoxaparin preoperatively (30 mg) or postoperatively (40 mg) every 12 or 24 hours or upon discharge (30 mg every 24 hours for 10 days). RESULTS: Overall, there were 6 (0.9%) pulmonary embolisms (PE) and 1 (0.1%) occurrence of deep vein thrombosis (DVT); all but 1 occurred after the cessation of thromboprophylaxis. The highest incidence of VTE was at Center B, which did not administer perioperative thromboprophylaxis (1 DVT and 2 PEs). There were 6 (0.9%) severe bleeding complications: 3 at center D and 3 at center E. In Center B, 2 deaths were recorded (0.3%): 1 due to sepsis and 1 due to bleeding, with both occurring after thromboprophylaxis was discontinued. CONCLUSION: The administration of enoxaparin, in various dosing regimens, is safe for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery. Fewer events occurred with perioperative prophylaxis initiated in the hospital. Because all thromboembolic events occurred after the cessation of thromboprophylaxis, extended thromboprophylaxis may be of value.

Adult↗

Enoxaparin and dalteparin in unstable angina: new indication. Enoxaparin: a reference treatment. Dalteparin: no better than unfractionated heparin.

(1) Enoxaparin and dalteparin are the only low-molecular-weight heparins so far approved for the treatment of unstable angina and non Q-wave myocardial infarction. (2) In two trials involving over 7,000 patients with unstable angina or non Q-wave myocardial infarction, the enoxaparin + aspirin combination was more effective than the unfractionated heparin + aspirin combination in reducing the risk of death, myocardial infarction or angina relapse. (3) In the same indication another trial showed no significant difference between the dalteparin + aspirin combination and the unfractionated heparin + aspirin combination on the basis of the same end point. (4) The dose must be calculated precisely according to bodyweight, as there is a severe risk of bleeding if the recommended dose is exceeded. (5) Continued enoxaparin therapy after clinical stabilisation has no supplementary benefit compared with aspirin alone.

Angina, Unstable↗

A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. The Enoxaparin in Medicine Study Group.

A multicenter, randomized double-blind study compared in two parallel groups the efficacy and safety of a low molecular weight heparin (LMWH) enoxaparin 20 mg once daily, with unfractionated heparin (UFH) 5000 IU twice daily, administered subcutaneously for 10 days, in the prevention of venous thrombosis disease in 442 hospitalized elderly patients bedridden for an acute medical illness. The main efficacy endpoint was defined as the occurrence of venous thrombosis, diagnosed by a daily fibrinogen uptake test, and/or documented clinical pulmonary embolism. Intention-to-treat analysis of efficacy showed that the incidence of venous thromboembolic events was low: 4.8% (10/207) in the LMWH group (9 episodes of isotopic venous thrombosis and one of scintigraphic pulmonary embolism), and 4.6% (10/216) in the UFH group (10 episodes of isotopic venous thrombosis). The two treatments were equivalent, where equivalence was defined as a maximum difference of 7% between the two groups (p = 0.0005). There were no significant differences in terms of safety between the 216 patients in the LMWH group and the 223 patients in the UFH group who received at least one injection of the randomized treatment. During the study period, 15 patients (3.4%) died (7 in the LMWH group and 8 in the UFH group): 2 sudden deaths, one in each group including one case in which pulmonary embolism could not be excluded since no autopsy was performed, and 13 others deaths unrelated to the study treatments. Six patients (1.4%) presented a bleeding complication: 2 (0.9%) in the enoxaparin group (one major and one minor hemorrhage), and 4 (1.8%) in the UFH group (2 major and 2 minor hemorrhages). These results indicate that subcutaneous enoxaparin 20 mg once daily for 10 days is as effective and well tolerated as subcutaneous UFH 5000 IU twice daily in the prevention of venous thromboembolic disease in bedridden elderly in-patients presenting an acute medical illness.

Acute Disease↗

Use of subcutaneous enoxaparin compared to intravenous heparin and oral phenprocoumon in the setting of cardioversion--the ACE study (Anticoagulation in Cardioversion using Enoxaparin).

The mode and duration of anticoagulation in the setting of cardioversion of atrial fibrillation-either with or without guidance by transesophageal echocardiography (TEE)-is still an unresolved issue. Oral anticoagulation with warfarin or phenprocoumon is frequently used but may be associated with an increased risk of bleeding complications or, conversely, episodes of undercoagulation. Moreover, it takes several days to reach full anticoagulation with oral compounds. This phase may be covered with intravenous heparin but this requires prolonged hospitalization. Low-molecular weight heparin is an attractive alternative as it not only provides a safe and predictable level of anticoagulation with few side effects but can also be administered safely on an outpatient basis. In addition, anticoagulation monitoring is usually unnecessary. The ACE study (Anticoagulation in Cardioversion using Enoxaparin) compared the safety and efficacy of subcutaneous enoxaparin with intravenous heparin/oral phenprocoumon before and after cardioversion (stratified to TEE guidance or no TEE guidance). This article summarizes the study rationale and design. The results will be published shortly.

Administration, Oral↗

Low-molecular-weight heparin (enoxaparin) vs dextran 70. The prevention of postoperative deep vein thrombosis after total hip replacement. The Danish Enoxaparin Study Group.

A prospective randomized study compared the thromboprophylactic efficacy and safety of a low-molecular-weight heparin (LMWH), enoxaparin (40.6 mg subcutaneously once daily), with a standard regimen of dextran 70 in patients undergoing elective total hip replacement. Deep vein thrombosis was diagnosed by bilateral ascending phlebography 7 to 11 days after operation. Two hundred forty-six patients were included and 219 were eligible for analysis. Deep vein thrombosis was diagnosed in seven of 108 patients in the LMWH group and in 24 of 111 patients in the dextran group. Clinical symptoms of pulmonary embolism did not develop in any patients during the study. In the postoperative period, patients receiving LMWH had a lower blood loss in drains and required fewer blood transfusions than patients receiving dextran, although no significant differences were noted between the groups with respect to the total number of blood transfusions required. Bleeding events and adverse events did not differ between the groups. None of the patients died in hospital during the study. One patient in the LMWH group died at home 15 days after the operation. Three patients receiving dextran had development of symptomatic deep vein thrombosis after hospital discharge. In conclusion, enoxaparin was a more effective thromboprophylactic than a standard regimen of dextran in patients undergoing total hip replacement. The two regimens were equally safe under the clinical conditions.

Adult↗

The Essence Trial: Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI: A Double-Blind, Randomized, Parallel-Group, Multicenter Study Comparing Enoxaparin and Intravenous Unfractionated Heparin: Methods and Design.

Antithrombotic therapy reduces the risk of recurrent ischemic events in patients with unstable angina. The primary aim of the ESSENCE trial is to evaluate the efficacy of enoxaparin (low molecular weight heparin) versus unfractionated heparin, plus aspirin, in patients with rest angina or non-Q-wave infarction. This is a randomized, double-blind, placebo-controlled study of 3180 patients comparing enoxaparin, 1 mg/kg sc bid, with unfractionated heparin via continuous iv infusion to maintain the aPTT at 2 x control. Patients within 24 hours of the onset of acute myocardial ischemia without ST elevation are eligible, and trial therapy is administered for a minimum of 48 hours to a maximum of 8 days. Primary endpoints analyzed are death, myocardial infarction (MI), or recurrent angina at 14 days. Currently 3019 patients have been randomized in 10 countries. The mean age is 64 years, 33% are female, and 46% have had a prior MI. The overall event rates at 14 days are 1.7% mortality, 5.9% subsequent MI, and 17% recurrent angina. The composite triple endpoint rate is 23.6%. Recruitment should be complete by June 1996. The methods and design of the study are presented in this article.

Journal Article↗

Thrombocytosis after prophylactic administration of enoxaparin: unexpected findings in a Polish prospective multicenter trial on the efficacy and safety of enoxaparin in the prevention of postoperative thromboembolism.

BACKGROUND: Heparin-related thrombocytopenia is a common complication of heparin administration and therefore platelet count was monitored in our study. METHODS EXPERIMENTAL DESIGN: Prospective multicentre study. SETTING: 14 Departments of General, Thoracic or OrthopaedicSurgery, Poland. PATIENTS: 290 patients--150 general or thoracic surgery patients aged above 40 years, and 140 orthopaedic surgery patients aged between 18 and 60 years. INTERVENTIONS: All patients received 20 mg (general and thoracic surgery) or 40 mg of enoxaparin (orthopaedic surgery) once daily subcutaneously both before surgery and during postoperative immobilisation. MEASURES: Platelet count was evaluated prior to surgery and on the 5th, 7th, 11th and 15th day following the operation. RESULTS: There was neither thrombocytopenia nor heparin-induced thrombosis. Paradoxically, postoperative platelet count in most cases increased slightly but statistically significantly, but in some however, even above 600 G/l, nevertheless in these patients no thrombotic complications occurred. Postoperative thrombocytosis was greater in patients with neoplasms as well as those with excessive perioperative blood loss and transfusions. CONCLUSIONS: As platelet count was not the main topic of our study, the presented data should be regarded only as preliminary. Further investigations to resolve the cause of the observed phenomenon of thrombocytosis are therefore necessary.

Adolescent↗

Combination of enoxaparin and fibroblast growth factor-1 increases myocardial blood flow and capillary density after myocardial infarction in rabbits.

OBJECTIVE: The effect of enoxaparin and fibroblast growth factor-1 (FGF-1) on post-infarction capillary density and regional myocardial blood flow (RMBF) was examined. METHODS: New Zealand White rabbits received an intramyocardial injection of either physiological saline, FGF-1 + enoxaparin, FGF-1 or enoxaparin directly after ligation of the left anterior descending artery. RMBF and capillary density were investigated using fluorescent microspheres and histological examination. RESULTS: One week after infarction a significant difference in the number of capillaries could be demonstrated within the FGF-1 + enoxaparin group (p < 0.001 versus the control group), the FGF-1 group (p < 0.01) and the enoxaparin group (p < 0.05). Treatment with FGF-1 + enoxaparin resulted in a significantly increased number of capillaries compared to treatment with FGF-1 (p < 0.05) and enoxaparin (p < 0.05) alone. Additionally, all groups treated with FGF-1 and/or enoxaparin showed a significant increase of microvessel density in the treated ischemic border zone compared to the non-treated ischemic border zone (p < 0.001 for FGF-1 + enoxaparin, p < 0.01 for FGF-1, p < 0.05 for enoxaparin). RMBF was significantly increased within the FGF-1 + enoxaparin group compared to the control group (p < 0.05). Moreover, perfusion rates within the FGF-1 + enoxaparin-treated area did not significantly differ from the pre-infarction values. CONCLUSION: Treatment with either enoxaparin or FGF-1 or FGF-1 + enoxaparin resulted in increased microvessel growth. However, only the combination of enoxaparin with FGF-1 promotes capillary growth and RMBF. Thus, we conclude that enoxaparin enhances the angiogenic potential of intramyocardially injected FGF-1 in the acutely infarcted rabbit heart.

Animals↗

Bleeding complications with enoxaparin for deep venous thrombosis prophylaxis.

The safest and most efficacious method of deep venous thrombosis prophylaxis remains controversial. With the use of enoxaparin, a low-molecular-weight heparin, becoming ubiquitous in many institutions, we specifically examined bleeding complications related to its use. A case-control study was conducted on consecutive patients receiving enoxaparin prophylaxis after primary or revision total knee or total hip arthroplasty or hip hemiarthroplasty. Matched controls receiving no pharmacologic anticoagulation were identified. Patient and operative characteristics, hematologic values, and timing of enoxaparin dosing were analyzed as related to major and minor bleeding complications. A total of 152 procedures with enoxaparin and an equal number of control cases were included for a total of 304 patients. The enoxaparin group had a 23.7% total complication rate compared to 16.5% for the control group (P = .11). The power of the test was .35 and indicated that approximately 970 patients would need to be reviewed to have at least an 80% chance of finding a statistically significant difference. Major complications occurred in 5 patients (3.3%) in the enoxaparin group and 2 (1.3%) in the control group (P = .25, power = .21). Minor complications in the enoxaparin group were slightly higher but not significant at 20.4% versus 15.1% in the control group (P = .23). There were significantly fewer minor complications in the enoxaparin group after primary single-joint procedures (16.50%) than all other procedures (32.4%). Patients receiving the first dose of enoxaparin 10 hours or more postoperatively had significantly fewer complications (P = .05). The postoperative hematocrit drop was significantly greater for the enoxaparin group for all procedures (P = .003) as well as for primary single procedures (P = .0005). The postoperative transfusion requirement was significantly greater after primary single procedures (P = .02) in the enoxaparin group. One patient with an epidural catheter and receiving enoxaparin postoperatively developed an epidural hematoma. Although there were not significantly more complications with enoxaparin, there was evidence of significantly increased postoperative bleeding. The low-power analysis reveals that a large number of patients (970-1,700) are required to show a statistically significant difference in bleeding complications between the 2 groups. To minimize complications, a short period to allow initial hemiostasis postoperatively is recommended, as is preferential use of enoxaparin for primary single-joint replacements. Enoxaparin used in conjunction with an indwelling epidural catheter is not recommended.

Aged↗

Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review.

The development of treatments for acute neurodegenerative diseases (stroke and brain trauma) has focused on (i) reestablishing blood flow to ischemic areas as quickly as possible (i.e. mainly antithrombotics or thrombolytics for stroke therapy) and (ii) on protecting neurons from cytotoxic events (i.e. neuroprotective therapies such as anti-excitotoxic or anti-inflammatory agents for stroke and neurotrauma therapies). This paper reviews the preclinical data for enoxaparin in in vivo models of ischemia and brain trauma in rats. Following a photothrombotic lesion in the rat, enoxaparin significantly reduced edema at 24 h after lesion when the treatment was started up to 18 h after insult. Enoxaparin was also tested after an ischemic insult using the transient middle cerebral artery occlusion (tMCAO) model in the rat. Enoxaparin, 2 x 1.5 mg/kg i.v., significantly reduced the lesion size and improved the neuroscore when the treatment was started up to 5 h after ischemia. Enoxaparin, administered at 5 h after insult, reduced cortical lesion size in a dose-dependent manner. In permanent MCAO, enoxaparin (5 and 24 h after insult) significantly reduced lesion size and improved neuroscore. A slight and reversible elevation of activated partial thromboplastin time (APTT) suggests that enoxaparin is neuroprotective at a non-hemorrhagic dose. Traumatic brain injury (TBI) is often accompanied by secondary ischemia due in part to edema-induced compression of blood vessels. When enoxaparin, at 0.5 mg/kg i.v. + 4 x 1 mg/kg s.c., was administered later than 30 h after TBI, it significantly reduced edema in hippocampus and parietal cortex. At one week after TBI the lesion size was significantly reduced and the neurological deficit significantly improved in enoxaparin treated animals. Finally, the cognitive impairment was significantly improved by enoxaparin at 48 h to 2 weeks after TBI. The anticoagulant properties of unfractionated heparin and specifically enoxaparin can explain their anti-ischemic effects in experimental models. Furthermore, unfractionated heparin and specifically enoxaparin, have, in addition to anticoagulant, many other pharmacological effects (i.e. reduction of intracellular Ca2+ release; antioxidant effect; anti-inflammatory or neurotrophic effects) that could act in synergy to explain the neuroprotective activity of enoxaparin in acute neurodegenerative diseases. Finally, we demonstrated, that in different in vivo models of acute neurodegenerative diseases, enoxaparin reduces brain edema and lesion size and improves motor and cognitive functional recovery with a large therapeutic window of opportunity (compatible with a clinical application). Taking into account these experimental data in models of ischemia and brain trauma, the clinical use of enoxaparin in acute neurodegenerative diseases warrants serious consideration.

Animals↗

Enoxaparin: an update of its clinical use in the management of acute coronary syndromes.

UNLABELLED: Enoxaparin (enoxaparin sodium) is a low molecular weight heparin (LMWH) indicated for use in the treatment of ischaemic complications of unstable angina and non-Q wave myocardial infarction (MI). Unfractionated heparin (UFH) has for many years represented the standard in anticoagulant therapy for patients with acute coronary syndromes; however, recent studies suggest that enoxaparin is also a viable option for anticoagulant therapy in these patients. The ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) and the TIMI 11B (Thrombolysis in Myocardial Infarction) studies reported that twice daily enoxaparin was significantly more effective than a continuous infusion of UFH in reducing the composite triple endpoint of death, MI, or recurrent angina or urgent revascularisation. Follow-up of both patient populations showed continued benefit associated with enoxaparin. Enoxaparin has been compared with tinzaparin in the treatment of unstable coronary artery disease using a nonblind study design. There was no difference between treatment groups in the therapeutic endpoints. Three nonblind studies have also compared the effects of enoxaparin and UFH in patients receiving thrombolytic therapy following acute MI. The HART II (Heparin and Aspirin Reperfusion Therapy), the ASSENT 3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) and the ENTIRE-TIMI 23 (Enoxaparin and Tenecteplase with or without glycoprotein IIb/IIIa Inhibitor as Reperfusion strategy in ST Elevation MI - Thrombolysis in Myocardial Infarction) studies have revealed that enoxaparin in combination with alteplase or tenecteplase is at least equivalent (HART II and ENTIRE-TIMI 23), and possibly superior (ASSENT 3) to UFH. Enoxaparin is administered as a twice-daily subcutaneous injection. In contrast, UFH is administered as an intravenous infusion which requires routine monitoring of the activated partial thromboplastin time to ensure adequate levels of anticoagulation are maintained. During the acute phase of the the ESSENCE and TIMI 11B studies, the incidence of major bleeding was similar in patients receiving enoxaparin to that in patients receiving UFH. In contrast, the rates of minor bleeding were higher in patients receiving enoxaparin than in those receiving UFH throughout these studies. CONCLUSIONS: Data from the ESSENCE, TIMI 11B and ASSENT 3 studies have prompted calls for those LMWHs which have been shown to be superior to UFH, to be considered as first choice treatment for anticoagulation in unstable coronary syndromes. To date, these suggestions are not reflected in current guidelines which consider UFH and LMWHs equally. Irrespective, the clinical data reported in this review support the use of enoxaparin in the treatment of acute coronary syndromes. These data suggest that enoxaparin shows certain clinical and practical advantages over standard treatment with UFH and represents an important development in the treatment of acute coronary syndromes.

Acute Disease↗

A randomized comparative study of using enoxaparin instead of unfractionated heparin in the intervention treatment of coronary heart disease.

BACKGROUND: Low molecular weight heparin (LMWH) was more effective than unfractionated heparin (UFH) in treating acute coronary syndrome (ACS). However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention (PCI) instead of UFH. This study aimed to evaluate the efficacy and safety of using enoxaparin instead of UFH in the intervention treatment of patients with coronary heart disease (CHD). METHODS: From October 2003 to Febuary 2005, 966 patients with CHD were enrolled into this study. Among 966 patients, 455 patients received the PCI, including 283 patients with Non-ST segment elevation ACS (NSTEACS), 511 patients did not received PCI due to mild, moderate lesions or were suitable for coronary artery bypass graft (CABG). The 966 patients were randomized to enoxaparin group (484 patients) and UFH group (482 patients). Patients in the enoxaparin group were given enoxaparin at least twice subcutaneously (1 mg/kg, q12 h) before catheterization. Plasma anti-Xa activity was determined 1 - 8 hours after the last dose of enoxaparin was determined. The catheterization was performed within 8 hours after the last dose of enoxaparin. The sheath was removed immediately after the procedure. Patients in the UFH group were given UFH 25 mg intravenously before coronary angiography. Additional 65 mg was given intravenously if PCI was to be performed. The sheath was removed 4 hours after the procedure. RESULTS: A total of 227 patients in the enoxaparin group and 228 patients in the UFH group received PCI. In the enoxaparin group, one patient developed acute thrombosis during PCI and resulted in acute myocardial infarction (AMI), no acute or subacute thrombosis was found during hospitalization. In the UFH group, no acute or subacute thrombosis occurred during PCI procedure and hospitalization. Therefore, the incidence of major adverse cardiovascular events (MACEs) during the hospitalization was 0.44% in the enoxaparin group and 0 in the UFH group. In the enoxaparin group, the sheath was removed immediately after the procedure and 8 patients had hematoma on the puncture site. In the UFH group, the sheath was removed 4 hours after the procedure and 20 cases had hematoma on the puncture site. The incidence of hematoma on the puncture site was significantly higher in the UFH group than that in the enoxaparin group (P < 0.05). Anti-Xa activity was determined in 174 patients in LMWH group. The mean anti-Xa activity was (0.87 +/- 0.23) U/ml, and 94.8% of them had anti-Xa activity >0.5 U/ml and 6.9% of the patient >1.2 U/ml. There was no death and AMI occurred in enoxaparin group, but one patient had AMI caused by subacute thrombosis in UFH group during 30-day follow-up. MACE rate at 30-day follow-up was 0 in enoxaparin group and 0.43% in UFH group. CONCLUSIONS: The results of the study suggest that it is safe and efficient to give enoxaparin at least twice before the PCI procedure, and the sheath can be removed immediately after PCI. For NSTEACS patient who has received enoxaparin more than twice during the hospitalization can undergo PCI directly and no UFH is necessary before or during PCI.

Angioplasty, Balloon, Coronary↗

Enoxaparin. A review of its clinical potential in the management of coronary artery disease.

UNLABELLED: Enoxaparin (enoxaparin sodium) is a low molecular weight heparin (LMWH) that is widely used in the prevention of deep venous thrombosis and pulmonary embolism in patients undergoing orthopaedic or general surgery. Its efficacy in these indications has led to study of its use in patients with coronary artery disease, particularly those with unstable angina, who have a high risk of myocardial infarction and death. A double-blind multicentre study [ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events)] showed that subcutaneous enoxaparin was more effective than intravenous unfractionated heparin (UFH) in reducing the incidence of the composite end-point of death, myocardial infarction or recurrent angina after 14 days in 3171 patients with recent-onset resting angina (i.e. unstable angina). There were no statistically significant between-group differences for the secondary end-point of death or myocardial infarction. Preliminary reports of long term follow-up data indicate that the clinical benefit of enoxaparin over UFH is maintained after 1 year. The only significant difference in tolerability between enoxaparin and UFH in ESSENCE was for minor haemorrhage (mostly injection-site ecchymosis), which was more common with the LMWH. Prospective pharmacoeconomic substudies of the ESSENCE trial suggest that total medical costs (including those for subsequent revascularisation procedures) for enoxaparin treatment are lower than those for UFH. The ESSENCE study is the first double-blind trial to show that a LMWH is more effective than UFH in patients with unstable angina. The superiority of enoxaparin was attributable mainly to its effects on recurrent angina. The level of anticoagulation achieved in the UFH group raises a number of issues which might have affected the apparent relative efficacy of enoxaparin and UFH. Preliminary data suggest that enoxaparin is at least as effective as UFH in reducing the incidence of subsequent cardiac events in patients receiving thrombolysis for acute myocardial infarction, and a randomised comparison with no additional treatment (other than aspirin) has demonstrated its efficacy in this indication. Enoxaparin has been ineffective in preventing restenosis after angioplasty CONCLUSIONS: The ESSENCE study has shown that enoxaparin is more effective than UFH in patients with unstable angina. Although clarification of some methodological issues would be beneficial, the available efficacy data, together with the practical advantages of LMWHs in general, suggest that enoxaparin is an effective and convenient means of treating unstable angina and should provide cost savings compared with UFH.

Angina, Unstable↗

Enoxaparin. A pharmacoeconomic appraisal of its use in thromboembolic prophylaxis after total hip arthroplasty.

Total hip arthroplasty (THA) is a major orthopaedic procedure with a high risk of postoperative thromboembolism. Increasing demand for this type of surgery, together with its high cost, has led to examination of means by which the cost of THA may be minimised. Current clinical opinion favours the use of suitable pharmacological thromboprophylaxis in patients undergoing THA; such prophylaxis may be provided with subcutaneous standard unfractionated heparin (UFH), oral warfarin or subcutaneous low molecular weight heparin (LMWH). Traditionally, LMWHs have been perceived as being more expensive to use than UFH or warfarin because of their relatively high acquisition cost. However, recent pharmacoeconomic data have shown that cost savings are possible when LMWHs are used. This is attributed mainly to reduced frequency of administration, reductions in costs associated with diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and the lack of need for laboratory monitoring of blood coagulation parameters. LMWHs have proportionally less anti-factor IIa (antithrombin) activity relative to anti-factor Xa activity than UFH. Enoxaparin, a LMWH with a mean molecular weight of 4 to 5kD, is reported to have approximately 5 times less activity against thrombin than UFH, for equivalent anti-factor Xa activity. Randomised clinical trials in patients undergoing THA have shown enoxaparin to be at least as effective as UFH in the prevention of DVT and PE, with consistent trends towards a lower incidence of DVT with enoxaparin than with UFH. Similar rates of haemorrhagic complications were reported for enoxaparin and UFH in most trials, although a significantly higher total transfusion requirement was reported for UFH than for enoxaparin in a double-blind study. A significantly higher incidence of bleeding was observed with UFH than with enoxaparin in another study, with similar transfusion requirements for both treatment groups. Cost comparisons in which costs were assigned retrospectively to clinical data have shown cost advantages for LMWHs in general over UFH when costs of administration, hospital bed occupancy and laboratory/radiology procedures are calculated. Cost savings with LMWHs were attributed mainly to reductions in the cost of managing thromboembolic complications in patients receiving these drugs. One meta-analysis showed a saving of $US50 000 (1993 figures) for LMWH over UFH (both subcutaneously twice daily) for every 1000 patients. Subcutaneous enoxaparin at a dosage of 30mg twice daily was shown to be more cost effective than oral warfarin in the prophylaxis of DVT and PE in 2 North American studies in which costs were related to outcomes. One study comprised the application of a decision analysis to a hypothetical group of 10 000 patients; an incremental cost effectiveness of $US12 288 (1993 figures) per death averted was reported for enoxaparin. Enoxaparin was also associated with an overall incremental cost effectiveness of $Can29 140 (1992 figures) per year of life saved (YLS) in the other study, in which costs were applied to clinical data obtained retrospectively from 10 randomised trials. Although no cost-effectiveness analyses have been carried out to compare enoxaparin with UFH, a UK cost comparison reported an overall cost saving of pounds 20 per patient (figures from 1989 to 1990) with enoxaparin 40mg once daily subcutaneously over subcutaneous UFH 5000IU 3 times daily. It has also been suggested that the use of once- or twice-daily enoxaparin in preference to UFH may reduce the overall length of hospital stay; a significant difference emerged in 1 analysis (9.9 or 9.5 vs 11.3 days). Pharmacoeconomic data therefore support the use of enoxaparin as an effective thromboprophylactic treatment with potential cost advantages over warfarin and UFH. Cost-effecti

Anticoagulants↗