1. Impact of Anticoagulation Regimens on Sheath Management and Bleeding in Patients Undergoing Elective Percutaneous Coronary Intervention in the STEEPLE Trial Richard Gallo, Steven R. Steinhubl, Harvey D. White, and Gilles Montalescot for the STEEPLE Investigators Catheterization and Cardiovascular Interventions 73:319-325 (2009) 1

2. Vascular access site complications, including hematoma and rebleeding remain a common and costly complication, increasing hospital stay, patient discomfort, and immediate, as well as long-term, mortality Predictors of bleeding are determined by patient-related factors such as advanced age, female sex, low body weight, and renal insufficiency as well as by the choice of antithrombotic regimen the time of sheath removal (immediate, activated clotting-time (ACT)- guided, or delayed) and the sheath size 2 Introduction

3. Encouraging results with newer pharmacological approaches, such as enoxaparin (a low-molecular-weight heparin), fondaparinux, and bivalirudin, as well as with the use of radial, as opposed to femoral- access have recently demonstrated marked reductions in vascular access site complications with an immediate and significant impact on length of hospital stay The SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial enoxaparin was associated with a significant reduction in major bleeding enoxaparin had more predictable anticoagulation levels compared with UFH in patients undergoing elective PCI 3 Introduction

4. Objective The objective of this subanalysis of the STEEPLE trial was to assess how anticoagulation with enoxaparin or UFH regimens influences sheath management and non-CABG-related bleeding in elective PCI patients 4

5. Methods Patients older than 17 years of age scheduled for elective PCI with a femoral approach 124 sites in nine countries Excluded from the trial were patients received recent thrombolysis were treated with a parenteral antithrombotic agent before PCI were at increased risk for bleeding had a known hypersensitivity to any of the drugs used in the study 5

6. Methods Treatment Protocol Eligible patients were randomly assigned to receive an intravenous bolus of UFH, adjusted for ACT according to current guidelines intravenous enoxaparin at a dose of 0.5 or 0.75 mg/kg were prestratified according to planned use of GP IIb/IIIa inhibitors Patients who were assigned to either enoxaparin group received a single intravenous bolus of enoxaparin, without anticoagulation monitoring, after sheath insertion and immediately before undergoing PCI When procedures were prolonged by more than 2 hr, an additional bolus of enoxaparin (half the original dose) was recommended. 6

7. Methods Treatment Protocol Patients randomized to UFH who were not receiving concurrent GP IIb/IIIa inhibitors were given an initial intravenous UFH bolus of 70-100 IU/kg to achieve a target ACT of 300-350 sec Patients who received concurrent GP IIb/IIIa inhibitors a lower initial bolus of UFH of 50-70 IU/kg was given to achieve a target ACT of 200-300 sec Additional boluses of UFH were given before the start of PCI and readministered during the procedure in those patients who did not reach the lower limit of the ACT target 7

8. Sheath Removal Recommendations In the enoxaparin 0.5 mg/kg group, sheath removal was recommended immediately after the end of PCI when sheath sizes 5-6 Fr were used 4-6 hr after the end of PCI when the sheath size was 7 Fr or larger In the enoxaparin 0.75 mg/kg group, sheath removal was recommended 4-6 hr after the end of PCI, regardless of size In patients receiving UFH, sheath removal was recommended at an ACT of 150-180 sec 8 Methods

9. Endpoints The occurrence of major or minor bleeding, not related to CABG, during the first 48 hr after the index PCI was recorded according to prespecified definitions outlined in Table I 9

10. 10 - GP IIb/IIIa inhibitors were used in 433 (40.5%), 499 (40.6%), and 491 (39.9%) patients - closure devices were used in 1,356 (38.4%) patients - sheath size of less than 7 Fr in 2,752 (78.0%) patients - early sheath removal (<30 min) in 1,455 (41.2%) patients

11. 11 - Use of a closure device did not affect the overall incidence of major and minor bleeding (6.9% vs. 7.3%) - a trend toward greater non-CABG-related major and minor bleeding rates with increased sheath size (6.8% [<7 Fr] vs. 8.6% [7 Fr]; P = 0.112)

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15. Treatment with enoxaparin simplifies sheath management in patients undergoing PCI because no monitoring of anticoagulation is required before sheath removal Early femoral sheath removal in patients receiving enoxaparin was associated with a significant reduction in non-CABG-related major and minor bleeding, compared with UFH The incidence of non-CABG-related major and minor bleeding events was similar when the time between the end of the procedure and sheath removal was more than 2 hr 15 Conclusions

16. In summary, the results of this subanalysis of the STEEPLE trial demonstrate that compared with UFH, enoxaparin significantly reduced the incidence of non-CABG-related major and minor bleeding when used in conjunction with smaller sheath sizes, closure devices, and early femoral sheath removal 16 Conclusions