Gender-based outcomes after paclitaxel-eluting stent implantation in patients with coronary artery disease.

OBJECTIVES: We sought to determine whether gender influences the results of paclitaxel-eluting stent implantation. BACKGROUND: The TAXUS-IV trial demonstrated the safety and effectiveness of the slow-release, polymer-based, paclitaxel-eluting TAXUS stent compared to bare-metal stents in patients undergoing elective coronary intervention. Whether these results are generalizable to women is not known. METHODS: A total of 1,314 patients with coronary lesions 10- to 28-mm long in 2.5- to 3.75-mm vessels were randomized to TAXUS stent versus bare-metal EXPRESS stents (Boston Scientific Corp., Natick, Massachusetts). Outcomes examined were stratified by gender. RESULTS: A total of 662 patients (including 187 women) were assigned to the TAXUS stent, and 652 (180 women) received the control stent. Women were older than men, and had more hypertension, diabetes, renal insufficiency, unstable angina, and heart failure, but less smoking. Among patients receiving the TAXUS stent, women compared with men had higher unadjusted one-year rates of target lesion revascularization (TLR) (7.6% vs. 3.2%, p = 0.03), though female gender was not an independent predictor of TLR (odds ratio [OR] = 1.72 [95% confidence interval (CI) 0.68 to 4.37], p = 0.25). Moreover, restenosis rates were similar in men and women treated with the TAXUS stent (8.6% vs. 7.6%, respectively, p = 0.80), as was late loss (0.22 vs. 0.23 mm, p = 0.90). Compared to control stents, treatment with the TAXUS stent in women resulted in a significant reduction in nine-month restenosis (8.6% vs. 29.2%, p = 0.0001) and one-year TLR (7.6% vs. 14.9%, p = 0.02). The only independent predictor of freedom from restenosis in women was randomization to the TAXUS stent (OR = 0.28 [95% CI 0.11 to 0.74], p = 0.01). CONCLUSIONS: The benefits of the paclitaxel-eluting stent in reducing clinical and angiographic restenosis are generalizable to women.

Bailout use of platelet glycoprotein IIb-IIIa inhibition during coronary stent implantation: observations from the ESPRIT trial.

Glycoprotein (GP) IIb/IIIa inhibitors are often used as a rescue or bailout therapy to manage complications arising during percutaneous coronary intervention, rather than as prophylactic treatment. We sought to identify the characteristics and outcomes of patients requiring bailout treatment. The ESPRIT trial randomized 2,064 patients to receive eptifibatide or placebo starting immediately before percutaneous coronary intervention (PCI). Bailout therapy was used in 77 patients: 43 (4.2%) randomized to placebo and 34 (3.3%) to eptifibatide (p = 0.3). Bailout therapy for thrombosis was used more often in the placebo group (2.1% versus 1.0%; p = 0.03). Multivariable predictors of bailout included a greater than or equal to 90% stenosis, or visible thrombus on the baseline angiogram, and no aspirin pre-treatment before PCI. However, overall the model predicted bailout poorly (c-index = 0.64). The need for bailout cannot be reliably predicted using baseline characteristics. Patients experiencing complications have poor clinical outcomes despite bailout use of GP IIb/IIIa inhibitors.

Relationship of creatine kinase-myocardial band release to Thrombolysis in Myocardial Infarction perfusion grade after intracoronary stent placement: an ESPRIT substudy.

BACKGROUND: The etiology of creatine kinase-myocardial band (CK-MB) release after percutaneous coronary intervention (PCI) remains unclear. The goal of this study was to evaluate the relationship of both epicardial and tissue level perfusion at the completion of stent placement to CK-MB release after the procedure. Given the high rates of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after PCI, we hypothesized that abnormalities in tissue level perfusion would instead explain CK-MB release. METHODS: Data were drawn from the angiographic substudy of the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial of eptifibatide versus placebo in patients undergoing planned coronary stent implantation. In the substudy, cinefilms of 65 patients were analyzed by an angiographic core laboratory blinded to enzymatic and clinical outcomes. RESULTS: The release of CK-MB was not associated with TIMI grade 3 flow or the corrected TIMI frame count; 100% of patients had TIMI grade 3 flow at the completion of PCI. In contrast, tissue level perfusion using the TIMI myocardial perfusion grade (TMPG) was related to postintervention CK-MB release: patients with a closed myocardium (TMPG 0/1) or delayed myocardial perfusion (TMPG 2) had an average CK-MB release 2.2 +/- 2.7 times the upper limit of normal (n = 34), whereas those patients with normal myocardial perfusion (TMPG 3, n = 24) had CK-MB 0.8 +/- 0.6 times the upper limit of normal (P =.01). Although no patients with TMPG 3 sustained death/myocardial infarction/urgent target vessel revascularization or thrombotic bailout, 17.7% of patients with TMPG 0/1/2 did by 48 hours (P =.037). CONCLUSIONS: Impaired tissue level perfusion as assessed by the TMPG and not epicardial coronary blood flow is associated with CK-MB elevation after PCI. These data provide a pathophysiologic link between impaired tissue level perfusion, post-PCI infarction, and adverse clinical outcomes.

Comparative pharmacodynamic evaluation of eptifibatide and abciximab in patients with non-ST-segment elevation acute coronary syndromes: the TAM2 study.

BACKGROUND: The importance of the relationship between clinical outcome and degree of platelet aggregation inhibition (PAI) achieved with the dosing regimens of GPIIb-IIIa inhibitors used in large trials in patients with non-ST segment elevation (NSTE) acute coronary syndromes (ACS) is increasingly appreciated. In the PURSUIT trial, eptifibatide treatment that consistently provided >80% PAI was associated with clinical benefit at 30 days and 6 months. The GUSTO IV ACS trial, however, did not show any effect of abciximab on 30-day outcomes. This difference might be due to variability of antiplatelet effects of these drugs. As previous studies found, a 12 hr abciximab infusion had <80% PAI, particularly at 6 and 12 hr. These studies did not evaluate PAI with a longer, 24-hour infusion as used in GUSTO IV ACS. METHODS: We conducted a prospective study in 40 patients with NSTE ACS prior to catheterization or coronary intervention at 3 centers using the PURSUIT dose of eptifibatide (180/2.0) [DOSAGE ERROR CORRECTED] and the GUSTO IV dose of abciximab (0.25, 0.125). Blood samples were collected at baseline, and during the infusion at 10 min, 1 hr, 6 hr, 8 hr, 12 hr, 18 hr, and 24 hr. Measurements of ex vivo light transmission aggregometry (LTA) were performed using PPACK anticoagulant and 20 microM ADP agonist. Receptor Occupancy (RO) was also determined in a subset of patients. RESULTS: Eptifibatide achieves higher PAI during the entire infusion period than abciximab (p<0.01). At 10 min, average PAI with eptifibatide and abciximab was 88% and 80%, respectively, 95% and 79% at 6 hr, and 97% and 79% at 24 hr. There was also more variability in individual patient response to abciximab. Although average RO for eptifibatide was similar to that of abciximab at 10 min, 67% versus 69%, respectively, average RO was higher in the eptifibatide cohort at all subsequent timepoints. By 24 hr, average RO for eptifibatide was 86%, whereas abciximab averaged 67%. CONCLUSION: These data support the hypothesis that differences in clinical outcomes of large GPIIb-IIIa trials in patients with NSTE ACS may be related to the consistency and potency of antiplatelet effects of the dosing regimens used.