Carotid Artery Stenting and Intracranial Thrombectomy for Tandem Cervical and Intracranial Artery Occlusions.

BACKGROUND: It remains controversial whether carotid artery stenting (CAS) is needed in cases of tandem cervical internal carotid artery occlusion (cICAO) and intracranial large vessel occlusion (LVO). OBJECTIVE: To investigate the efficacy and safety of CAS in combination with endovascular thrombectomy (CAS-EVT) in cICAO-LVO patients and to compare its outcomes with those of EVT without CAS (EVT-alone). METHODS: We identified all patients who underwent EVT for tandem cICAO-LVO from the prospectively maintained registries of 17 stroke centers. Patients were classified into 2 groups: CAS-EVT and EVT-alone. Clinical characteristics and procedural and clinical outcomes were compared between 2 groups. We tested whether CAS-EVT strategy was independently associated with recanalization success. RESULTS: Of the 955 patients who underwent EVT, 75 patients (7.9%) had cICAO-LVO. Fifty-six patients underwent CAS-EVT (74.6%), and the remaining 19 patients underwent EVT-alone (25.4%). The recanalization (94.6% vs 63.2%, P = .002) and good outcome rates (64.3% vs 26.3%, P = .007) were significantly higher in the CAS-EVT than in the EVT-alone. Mortality was significantly lower in the CAS-EVT (7.1% vs 21.6%, P = .014). There was no significant difference in the rate of symptomatic intracranial hemorrhage between 2 groups (10.7 vs 15.8%; P = .684) and according to the use of glycoprotein IIb/IIIa inhibitor (10.0% vs 12.3%; P = .999) or antiplatelet medications (10.2% vs 18.8%; P = .392). CAS-EVT strategy remained independently associated with recanalization success (odds ratio: 24.844; 95% confidence interval: 1.445-427.187). CONCLUSION: CAS-EVT strategy seemed to be effective and safe in cases of tandem cICAO-LVO. CAS-EVT strategy was associated with recanalization success, resulting in better clinical outcome.

Percutaneous Non-Stenting Approach for Distal Simultaneous Multivessel Acute Coronary Occlusions.

The occurrence of distal coronary lesions causing simultaneous occlusion of two coronary arteries in the setting of ST elevation myocardial infarction is a rare occurrence. This can occur due to simultaneous plaque rupture at more than one site or embolisation in coronary arteries. We describe a case of a middle-aged man who presented with acute inferoposterior lateral wall ST elevation myocardial infarction with simultaneous occlusion of distal left anterior descending artery and distal left circumflex artery on angiogram. The patient was treated with intracoronary streptokinase, followed by glycoprotein (GP) IIb/IIIa inhibitor and Factor X inhibitor (Rivaroxaban) with full resolution of flow in the distal vessels. Thus, coronary lesions, not amenable to stenting, can be dealt percutaneously, using a combination of old and newer pharmacological agents without stenting.

Intravenous GPIIb/IIIa Inhibitor for Secondary Prevention of Shunt Thrombosis in a Pediatric Patient.

Thrombosis occurs after aortopulmonary shunting in children despite the use of heparin and oral antiplatelet agents. We describe the use of an intravenous antiplatelet agent for secondary prevention of shunt thrombosis without adverse events. Platelet mapping was used to monitor the effects and demonstrated the rapid onset of platelet inhibition.

The prognostic role of renal dysfunction in STEMI patients submitted to primary PCI with adjunctive thrombus aspiration.

AIM: The present investigation was aimed at assessing the prognostic impact of renal dysfunction rate in STEMI patients submitted to thrombectomy (TP). METHODS: Out of 1268 consecutive ST elevation myocardial infarction (STEMI) patients treated with pPCI from January 1rst 2004 to December 31th 2012 in our hospital 671 patients (52.9%) underwent adjunctive thrombus aspiration and constituted the study population. Patients were divided into three groups according to eGFR: group 1 included patients with eGFR>60 mL/min/m2, group 2 eGFR>30 mL/min/m2 and <60 mL/min/m2, group 3 eGFR<30 mL/min/m2. The rate of utilization of thrombectomy, the rate of pPCI failure and the incidence of major bleeding were assessed in each subgroup. Patients in group 3 and group 2 were less likely to be submitted to TP, while more than 50% of patients with normal eGFR underwent TP (overall P=0.019). The rate of pPCI failure was significantly higher in group 2 and 3 when compared to group 1 (P=0.002). Worsening renal failure was associated with a higher mortality rate both at ICCU and at 1 year follow-up (P<0.001 and P<0.001, respectively). A higher incidence of major bleedings was reported in group 2 and group 3, despite the lower administration of glycoprotein IIb/IIIa inhibitors (P<0.001). Moderate and severe renal impairment was associated with a higher mortality rate both at ICCU and at 1 year follow-up (P<0.001 and P<0.001, respectively). CONCLUSION: Thrombus aspiration is less like to be performed among patients with impaired renal function. Despite thrombus aspiration patients with reduced eGFR showed a higher incidence of pPCI failure.

Routine early eptifibatide versus delayed provisional use at percutaneous coronary intervention in high-risk non-ST-segment elevation acute coronary syndromes patients: an analysis from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome trial.

AIMS: In the EARLY ACS trial, routine early eptifibatide was not superior to delayed provisional use at percutaneous coronary intervention (PCI); however, among PCI-treated patients, numerically fewer ischemic end points occurred in the upstream eptifibatide group. We sought to further explore this finding using methods for examination of treatment effect in this postrandomization subgroup. METHODS AND RESULTS: Of 9,406 patients in the EARLY ACS primary analysis cohort, 9,166 (97.4%) underwent coronary angiography. We used Cox proportional hazards regression modeling, with PCI as a time-dependent covariate, to examine the effect of routine early versus delayed provisional eptifibatide among 5,541 patients undergoing PCI and to explore the interaction between treatment with PCI and randomized treatment strategy. After multivariable adjustment, compared with delayed provisional use, routine early eptifibatide was associated with lower rate of 30-day death or myocardial infarction (MI) after PCI (hazard ratio [HR] 0.80, 95% CI 0.68-0.95) but not with medical management (HR 0.97, 95% CI 0.74-1.29); PCI × randomized treatment interaction term P = .24. Excluding PCI-related MI, the adjusted HR for 30-day death or MI for routine early eptifibatide versus delayed provisional use was 0.80 (95% CI 0.60-1.08) for post-PCI treatment and 1.01 (95% CI 0.79-1.34) for medical management; PCI × randomized treatment interaction term P = .28. CONCLUSIONS: Consistent with previous literature, upstream treatment with eptifibatide was associated with improved outcomes in high-risk non-ST-segment elevation acute coronary syndrome patients treated with PCI; however, a nonsignificant interaction term precludes a definite conclusion.

Salvage of distal non-target coil embolization with stent placement and intravenous eptifibatide in a ruptured, unsecured, atypical aneurysm.

INTRODUCTION: Small aneurysms may be challenging to embolize. In cases of subarachnoid hemorrhage (SAH) where treatment is delayed, physicians may have to balance the risks of certain required therapies (antiplatelet agents) with the risk of rerupture. We describe a case of a technically challenging anterior cerebral artery aneurysm requiring eptifibatide infusion prior to definitive aneurysm treatment. CASE REPORT: A 57-year-old woman with SAH, underwent coil embolization of a small fenestrated A1-A2 junction aneurysm. The procedure was complicated by downstream coil migration which was then treated with Enterprise stent placement in the pericallosal artery. This required subsequent infusion of a glycoprotein IIb/IIIa inhibitor until the aneurysm could be repaired surgically. CONCLUSIONS: Revascularization with a stent in a distal cerebral vessel may salvage inadvertent coil migration. Although it is undesirable to administer antiplatelet agents to patients with SAH, in these circumstances short acting agents may be used.

Relationship between the intensity of heparin anticoagulation and clinical outcomes in patients receiving glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction.

OBJECTIVES: We sought to determine the impact of the activated clotting time (ACT) in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with unfractionated heparin (UFH) and a glycoprotein IIb/IIIa inhibitor (GPI). BACKGROUND: UFH+GPI is commonly used during primary PCI for STEMI. UFH anticoagulation is titrated with ACT. METHODS: Patients randomized to UFH+GPI in HORIZONS-AMI who underwent primary PCI are included (N = 1,624). Initial UFH bolus was 60 IU kg(-1) (target ACT: 200-250 sec). Patients were divided into three tertiles of peak ACT (cutoffs 240 and 298 sec). The 30-day rates of major and minor bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE; MACE or major bleeding) were determined. RESULTS: Mortality at 30 days occurred in 2.2, 3.3, and 3.5% of patients in the low to high ACT tertiles, respectively (P(trend) = 0.22). Nor was the peak ACT significantly related to major bleeding, MACE or NACE. However, minor bleeding was increased in the highest ACT tertile (14.7% vs. 14.2% vs. 19.4%, P(trend) = 0.04). By multivariable analysis peak ACT was not significantly related to major bleeding, mortality, MACE, and NACE but was a significant independent predictor of minor bleeding (odds ratio = 1.027 [1.013, 1.042], P < 0.001, for each 10 sec increase in ACT). CONCLUSIONS: In patients undergoing primary PCI for STEMI treated with UFH+GPI, the peak procedural ACT achieved does not have a substantial effect on major bleeding, mortality, or MACE, although lower peak ACT is associated with less minor bleeding.

[Primary coronary angioplasty for myocardial infarction--the view of the cardiologic surgeon]. / L'angioplastie primaire dans l'infarctus du myocarde vue par l'angioplasticien.

The aim of this article is not to present a general academic review on primary angioplasty in patients with ST-elevation myocardial infarction, but rather to focus on some practical points that directly concern cardiologists who perform primary percutaneous interventions in these patients. We detail recent data about the use of the radial artery approach, thromboaspiration, new oral inhibitors of P2Y12, selective use of anti-GPIIb/IIIa, high dose of peri-procedural statin therapy, choice of the best stent, and the best approach for treating non-culprit lesions in patients with multivessel coronary artery disease. The changes observed in the overall management of patients undergoing primary PCI for ST-elevation myocardial infarction are likely to have participated in the decrease in mortality observed in several registries. New European guidelines on the management of STEMI, taking into account these diverse aspects, have just been published.

Safety of "bridging" with eptifibatide for patients with coronary stents before cardiac and non-cardiac surgery.

Patients with previously implanted coronary stents are at risk for stent thrombosis if dual-antiplatelet therapy is prematurely discontinued. Bridging with a glycoprotein IIb/IIIa inhibitor has been advocated as an alternative, with few supporting data. The aim of this study was to determine the safety of such a strategy by retrospectively analyzing bleeding in 100 consecutive patients with previously implanted coronary stents who were bridged to surgery with eptifibatide after discontinuing thienopyridine therapy. A propensity-matched control comparison was performed for a subgroup of 71 patients who underwent cardiovascular surgery. Blood transfusions were required in 65% in the bridged group versus 66% in the control group (p = 0.86). The mean numbers of units transfused were 4.84 ± 6.93 and 3.65 ± 7.46, respectively (p >0.25). Rates of return to the operating room for bleeding or tamponade were 10% and 2.9%, respectively (p = 0.085). Increased rates of transfusion were noted for patients who received concomitant aspirin and/or intravenous heparin infusion. In conclusion, there does not appear to be any increase in the need for blood transfusions or rate of return to the operating room for patients being bridged with eptifibatide when thienopyridines are discontinued in the perioperative period, but concomitant use of additional antiplatelet or anticoagulant agents may increase transfusions and delays to surgery. Clinicians who are considering this strategy must weigh the risks of stent thrombosis versus bleeding.

Comparison of safety and efficacy of bivalirudin versus unfractionated heparin in high-risk patients undergoing percutaneous coronary intervention (from the Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin study).

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥ 1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.

Clinical outcomes of intracoronary eptifibatide bolus only versus intracoronary bolus and intravenous infusion of eptifibatide in primary percutaneous coronary intervention.

Intracoronary bolus of eptifibatide during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to result in higher local platelet glycoprotein IIb/IIIa receptor occupancy with improved microvascular perfusion. It is unclear whether intracoronary administration of eptifibatide in a larger patient population results in favourable clinical outcomes. We evaluated the safety and efficacy of two regimens of intracoronary eptifibatide (bolus only versus bolus followed by intravenous infusion) in patients undergoing primary PCI for ST-elevation MI. They were divided into two groups: Group A (n=67) who received fixed-dose intracoronary eptifibatide bolus only and Group B (n=88) who received intracoronary bolus and continuous intravenous infusion of eptifibatide for 18 h. The preliminary findings from our registry showed that both regimens were associated with good angiographic outcomes, few bleeding events and low in-hospital major adverse cardiac events. A large prospective randomized, multi-centre trial is needed to confirm our observation.

Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial.

BACKGROUND: Primary results of the HORIZONS-AMI trial have been previously reported. In this final report, we aimed to assess 3-year outcomes. METHODS: HORIZONS-AMI was a prospective, open-label, randomised trial undertaken at 123 institutions in 11 countries. Patients aged 18 years or older were eligible for enrolment if they had ST-segment elevation myocardial infarction (STEMI), presented within 12 h after onset of symptoms, and were undergoing primary percutaneous coronary intervention. By use of a computerised interactive voice response system, we randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomisation; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare metal stent (stent randomisation; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). We produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00433966. FINDINGS: Compared with 1802 patients allocated to receive heparin plus a GPI, 1800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5·9%vs 7·7%, difference -1·9% [-3·5 to -0·2], HR 0·75 [0·58-0·97]; p=0·03), cardiac mortality (2·9%vs 5·1%, -2·2% [-3·5 to -0·9], 0·56 [0·40-0·80]; p=0·001), reinfarction (6·2%vs 8·2%, -1·9% [-3·7 to -0·2], 0·76 [0·59-0·99]; p=0·04), and major bleeding not related to bypass graft surgery (6·9%vs 10·5%, -3·6% [-5·5 to -1·7], 0·64 [0·51-0·80]; p=0·0001) at 3 years, with no significant differences in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2257 patients who received a paclitaxel-eluting stent had lower rates of ischaemia-driven target lesion revascularisation (9·4%vs 15·1%, -5·7% [-8·6 to -2·7], 0·60 [0·48-0·76]; p<0·0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke or stent thrombosis. Stent thrombosis was high (≥4·5%) in both groups. INTERPRETATION: The effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary percutaneous coronary intervention. FUNDING: Boston Scientific and The Medicines Company.

Antiplatelet therapy in acute coronary syndromes.

Antiplatelet therapy is integral to the acute and long-term management of acute coronary syndromes (ACSs) and for minimizing the thrombotic complications of percutaneous coronary intervention (PCI). This article reviews the most commonly used antiplatelet agents in ACS therapy--aspirin, adenosine diphosphate (ADP)-receptor blockers, and glycoprotein IIb/IIIa inhibitors. More recent data are also reviewed on novel ADP-receptor blockers and thrombin inhibitors before addressing issues of adherence to antiplatelet regimens.

Changes in glycoprotein IIb/IIIa inhibitor excess dosing with site-specific safety feedback in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) initiative.

BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors can improve outcomes in patients with non-ST-segment elevation acute coronary syndromes but raise the risk of bleeding, particularly if dosed in excess. The impact of GP IIb/IIIa dosing feedback on safety and major bleeding is unknown. METHODS: Glycoprotein IIb/IIIa dosing feedback was added to the CRUSADE quarterly site reports in the first quarter of 2006. We describe GP IIb/IIIa use and dosing among 25,641 patients with non-ST-segment elevation acute coronary syndromes from the fourth quarter of 2005 to the fourth quarter of 2006. RESULTS: Eleven thousand eight hundred forty-six patients received GP IIb/IIIa inhibitors, including 4,031 women and 2,609 elderly patients (age, ≥75 years). Among GP IIb/IIIa-treated patients, unadjusted rates of excess GP IIb/IIIa dosing declined overall (26.4%-22.4%, Ptrend=.01) and among the elderly (65.6%-52.1%, Ptrend<.001). After adjustment, declines in excess dosing remained significant only for the elderly, although more than half of GP IIb/IIIa-treated elderly patients continued to receive excess dosing at the end of the study period (64.1%-51.3%, Ptrend<.001). There were concurrent declines in unadjusted major bleeding rates overall (9.6%-8.0%, Ptrend=.02), but declines among women (14.4%-11.5%, Ptrend=.08) and the elderly (17.1%-11.0%, Ptrend=.05) did not reach statistical significance. After adjustment for baseline characteristics and excess dosing, declines in major bleeding rates were no longer significant overall or for any subgroup. CONCLUSION: Within 9 months of initiating a safety feedback program, we observed early decreases in excess GP IIb/IIIa dosing among the elderly but minimal changes in excess dosing overall. Further work is needed to promote safe and effective medication use in vulnerable patients who are most at risk of harm.

Comparison of outcomes in patients > or =70 years versus <70 years after transradial coronary stenting with maximal antiplatelet therapy for acute coronary syndrome.

Elderly patients are at a higher risk for complications after percutaneous coronary intervention (PCI) when performed through the femoral approach. The impact of age on complications in patients treated using the transradial approach is not known. The bleeding and ischemic outcomes at 30 days, 6 months, 1 year, and 3 years after transradial PCI and maximal antiplatelet therapy were compared in 1,348 patients aged <70 or > or =70 years with acute coronary syndromes. All patients received aspirin and clopidogrel before catheterization, followed by abciximab at the time of PCI. Patients aged > or =70 years (n = 259 [19%]) had more hypertension, dyslipidemia, family histories, and previous coronary artery bypass grafting. Older patients had lower baseline hemoglobin, platelet, and creatinine clearance values, and they also more often had 2- or 3-vessel syndrome (p = 0.001), as well as longer procedure durations (p = 0.024). At 30 days, the rates of major adverse cardiac events and major bleeding were similar in older and younger patients. Only the incidence of gastrointestinal bleeding (p = 0.021) and mild to moderate access-site hematoma were higher in older patients (p = 0.036). The rates of major adverse cardiac events were also similar in the 2 age groups at 6 months (6% vs 9%, p = 0.08), 1 year (10% vs 13%, p = 0.22), and 3 years (19% vs 20%, p = 0.73), but mortality was significantly higher at 3 years in patients aged > or =70 years (p = 0.0031). In conclusion, age per se is not a predictor of major adverse cardiac events or major bleeding after transradial PCI with maximal antiplatelet therapy. However, older patients remain more prone to gastrointestinal bleeding and local hematoma compared to younger patients, and preventive measures need to be further investigated.

Survival benefit with concomitant clopidogrel and glycoprotein IIb/IIIa inhibitor therapy at ad hoc percutaneous coronary intervention.

OBJECTIVE: To study clinical outcomes in patients given glycoprotein (GP) IIb/IIIa inhibitors with concomitant clopidogrel at the time of ad hoc percutaneous coronary interventions (PCI). PATIENTS AND METHODS: We studied 30-day and long-term outcomes of patients undergoing elective or urgent PCI from March 1, 1998, to December 31, 2006, stratified by administration of GP IIb/IIIa inhibitors with concomitant clopidogrel treatment at the time of ad hoc PCI. RESULTS: The mean+/-SD age was 66.3+/-11.9 years in 5196 patients receiving compared with 67.8+/-11.8 years in 4681 patients not receiving a GP IIb/IIIa inhibitor (P<.001). Overall, 30-day unadjusted mortality was lower in patients who received a GP IIb/IIIa inhibitor (1.0% vs 1.2%; P=.22). Long-term mortality was significantly lower (P<.001) in patients receiving GP IIb/IIIa inhibitors at the time of PCI. After propensity analysis to adjust for the likelihood of receiving GP IIb/IIIa inhibitors on the basis of clinical, angiographic, and procedural characteristics, a significant reduction in 30-day mortality with GP IIb/IIIa inhibitor use was identified (hazard ratio, 0.56; 95% confidence interval, 0.36-0.87; P=.01). Kaplan-Meier analysis (median follow-up, 48 months) revealed a significant improvement in long-term survival in patients receiving a GP IIb/IIIa inhibitor at the time of ad hoc PCI that persisted after propensity adjustments (hazard ratio, 0.88; 95% confidence interval, 0.79-0.98; P=.021). Patients treated with drug-eluting stents showed a significant improvement in adjusted long-term mortality. CONCLUSION: In patients undergoing elective or urgent ad hoc PCI, coadministration of a GP IIb/IIIa inhibitor and dual antiplatelet therapy is associated with reduced risk-adjusted 30-day and long-term mortality.

Impact of anticoagulation levels on outcomes in patients undergoing elective percutaneous coronary intervention: insights from the STEEPLE trial.

AIMS: To determine the relationship between anticoagulation levels during percutaneous coronary intervention, and ischaemic events and bleeding. METHODS AND RESULTS: A sub-analysis from the STEEPLE trial was conducted. Pre-defined target anticoagulation levels were achieved in 86% of patients receiving enoxaparin, compared with 20% receiving unfractionated heparin (UFH) (P < 0.001). A significant relationship was observed between anti-Xa levels > 0.9 IU/mL and covariate-adjusted rate of non-coronary artery bypass graft-related major and minor bleeding [odds ratio (OR) 1.6, 95% CI 1.0-2.5 for each unit of anti-Xa; P = 0.03]; anti-Xa levels and covariate-adjusted incidence of death, myocardial infarction, or revascularization showed no significance (P = 0.47). Major bleeding increased significantly with an activated clotting time (ACT) > 325 s (OR 1.6, 95% CI 1.1-2.2 per 100 s; P = 0.04). A significant relationship with increasing ischaemic events was observed when ACT was < 325 s (OR 0.7, 95% CI 0.2-0.8 per 100 s; P = 0.006) indicating a narrow therapeutic window. CONCLUSION: Target anticoagulation levels were achieved more readily in patients receiving enoxaparin. An anti-Xa level of up to 0.9 IU/mL has a good safety and efficacy profile; poor achievement of target ACT with UFH makes assessing the optimal range difficult.