PubMed · 9505908
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P Glasziou. 1998. Using cost-effectiveness for subsidy decisions.. https://doi.org/10.1136/hrt.79.1.7
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OBJECTIVE: Activated platelets rapidly adhere to monocytes and upregulate the expression of tissue factor (TF), the major trigger of the coagulation cascade. In this study, we examined the effect of abciximab, a nonselective glycoprotein IIb/IIIa-receptor antagonist, on monocyte TF expression in thrombin receptor activator-stimulated whole blood in vitro. METHODS AND RESULTS: Abciximab (50 microg/mL) reduced the mass of platelets attached to monocytes, measured by the mean fluorescence intensity (MFI) of CD42b on CD14+ cells, 1 (CD42b, 471+/-197 versus 1073+/-217 MFI, mean+/-SD, P<0.05), 5, and 10 minutes after thrombin receptor activator stimulation of whole blood to the same extent as anti-P-selectin (50 microg/mL; 288+/-177 MFI, P<0.05) when determined by flow cytometry. In parallel, the expression of the platelet activation marker P-selectin colocalized with CD14+ monocytes was reduced up to 25% by abciximab at the same time points. Expression of monocyte TF antigen (CD14+/TF+, 39.9+/-8.7% versus 66.3+/-19.9%, P<0.05), chromogenic TF-activity (TF, 8.4+/-1.9 versus 13.2+/-2.8 U, arbitrary units, P<0.05), and TF mRNA was suppressed in the presence of abciximab as a consequence of reduced platelet mass attached to monocytes. CONCLUSIONS: Our data suggest that heterotypic monocyte-platelet aggregates are a target for abciximab, which suppresses monocyte TF because of a reduction of monocyte-platelet cross talk.
Previous evidence suggests that the monoclonal antibody abciximab may have a more potent anticoagulant effect than small-molecule glycoprotein (GP) IIb/IIIa inhibitors. We prospectively reviewed collected heparin dose, activated clotting time (ACT), and corresponding clinical outcome data from The Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET), a direct comparison of tirofiban versus abciximab in patients who underwent percutaneous intervention. Of the 4,809 patients enrolled in the trial, 3,739 patients (78%) had an ACT measured after the administration of GP IIb/IIIa and heparin (peak procedural ACT); this formed the population for the present study. Mean total heparin dose was 75 +/- 32 and 76 +/- 31 U/kg in the tirofiban and abciximab groups, respectively. The resultant mean peak ACTs were 296 +/- 91 and 299 +/- 89 seconds (p = 0.09). In a subset of patients with both baseline ACT (before any heparin or GP IIb/IIIa therapy) and peak procedural ACT measurements, the difference in ACT between these time points was 80 +/- 97 vs 82 +/- 101 seconds (p = 0.44) for the tirofiban and abciximab groups, respectively. After adjusting for patients' weight, weight-adjusted heparin dose, and method of ACT measurement in a multiple linear regression analysis, the type of GP IIb/IIIa inhibitor was not predictive of the peak ACT (p = 0.24). When stratified by ACT quartile, no statistically significant difference in bleeding or ischemic end points between the tirofiban and abciximab cohorts was observed. In this large contemporary percutaneous coronary intervention trial, there was no observed difference in the anticoagulant effect of tirofiban and abciximab, as measured by the ACT, or in the incidence of bleeding or ischemic complications in each ACT quartile.
BACKGROUND: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. METHODS AND RESULTS: NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile. CONCLUSIONS: The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.