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Out of context: Reply #24
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why not in the first frame of your flash .fla put something like this so it displayes text in a certain filed.
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text1 = "Challenging the Heparin Paradigm in Cardiology: The Evidence-Based Role of LMWHS";
text2 = "ObjectivesThere are three major learning objectives for this program. At the conclusion of the program, you should be enabled to: Differentiate unfractionated heparin (UFH) and LMWH pharmacology, monitoring and dosing. Assess UFH/LMWH clinical evidence in defining contemporary cardiovascular practice. Discuss evolving UFH/LMWH issues (e.g. dosing, safety, nomogram reliability/validity, economics.";
text3 = "Mechanisms of ActionThe mechanisms of action of UFH vs. agents such as LMWHs are primarily different because of the structural differences in the molecules. As shown in the graphic, LMWHs preferentially inhibit Xa whereas UFH exerts more of an effect on thrombin. ";
text4 = " Lab MonitoringConsidering the specific effects of LMWH and UFH on the coagulation cascade, they are best monitored using the coagulation tests shown in the table. Because UFH predominantly effects the intrinsic system as well as the levels of Xa and IIa, the aPTT is used most often to monitor therapy. The therapeutic range for aPTT with UFH must be validated in the individual lab using a specific reagent and instrument.The ACT test performed on whole-blood samples, is used most often in the cardiac cath lab or with CABG surgery.to monitor the effects of high dose UFH where the aPTT is not suitable. Consistent with the primary mechanism of action of LMWHs, when necessary the anticoagulant activity is best monitored using anti-Xa activity. However, anti-Xa activity is usually only monitored when LMWHs are administered in special populations such as in obese patients and those with significant renal impairment. The Enox test is a point-of-care test which can be used in the cath lab to insure adequate anticoagulant activity in this setting. The citrated clotting time (CCT) is the actual test measured by the Enox test.";
text5 = "Pharmacologic CharacteristicsThis slide summarizes the pharmacologic characteristics of the heparins.. One of the major advantages of LMWHs vs. UFH is that they exhibit a more predictable anticoagulant response. Because of their lower molecular weight and decreased binding to plasma proteins, the bioavailability is much better with LMWHs as shown in the table. Because of a decrease in plasma protein binding and binding to the endothelium, LMWHs have a half-life that is 2-4 times longer than UFH. The anti-Xa to IIa ratios of the LMWHs range from 1.9 for tinzaparin to 3.8 for enoxaparin, demonstrating a preferential effect on factor Xa vs. 1-1.2 for UFH due to its significant effect on thrombin. In addition, they exhibit a dose-independent clearance and are resistant to PF4 which promotes a more predictable anticoagulant response and established dosing in comparison to UFH where the clearance is dose-dependant and the drug is not resistant to PF4. aPTT monitoring is essential with UFH, whereas monitoring is not routinely needed with LMWHs. It is also noted in the table that UFH use is associated with elevated levels of vWf and a paradoxical increase in platelet aggregation compared to the LMWHs. ";
text6 = "Impact on AggregationAs depicted, platelet activation and aggregation is critically important in thrombosis, especially on the arterial side of the circulation. A study by Montalescot (July 2000 JACC) tested the hypothesis that different anticoagulants may produce different platelet effects and release of von Willebrand factor (vWf) in unstable angina patients. The early release of vWf has been reported in more than 80% of patients who had recurrent ischemia within 30 days of unstable angina.The release of vWf was compared in 154 unstable angina patients treated with enoxaparin, UFH, or dalteparin. As shown on the bar graph, vWf levels did not increase acutely in patients receiving enoxaparin. A serious rise in vWf was reported with UFH which differed significantly from the LMWH enoxaparin. Thus, anticoagulants do not provide the same protection with regards to vWf release which may have important prognostic implications and may explain different results observed in recent ACS clinical trials (e.g. ESSENCE, TIMI 11B, FRIC). ";
text7 = "Were the aPTT Ranges Validated?When we look at the use of UFH and aPTT levels in landmark trials such as the GUSTO-I study, patient outcomes such as the probability of death were correlated with aPTT levels. In this STEMI trial, the lowest probability of death was reported to be at aPTT levels between 50-70 seconds. The question becomes, however, were the aPTT levels in the study fully validated for the specific reagents and instrumentation used?. Also, even if the aPTTs were validated, can they be extrapolated to my institution? The answer is that they are not extrapolable and aPTTs must be individually validated in individual institutions. ";
text8 = "Suboptimal UFH Monitoring/DosingMonitoring UFH therapy using aPTT remains a clinical challenge. Traditionally the target aPTT has been 1.5-2.5 X the control. However, this aPTT range must be validated in the individual lab to ensure corresponding UFH serum levels of 0.2-0.4 IU.ml or anti Xa levels of 0.3-0.7 IU/ml. It should be appreciated that there have been dramatic changes in reagents and instruments over the past 25 years. Generally, the TPL reagents are much more sensitive today. With current therapeutic UFH dosing and levels, TPL reagents produce an aPTT ratio of 3.7-6.2; thus, underdosing often results using a ratio of 1.5-2.5 X control.Further, there are more than 300 different laboratory methods in use today. ";
text9 = "Suboptimal UFH Monitoring/DosingThe result of the changes in TPL sensitivity, instrumentation, and the myriad of lab methods is that there is immense variation in responsiveness to UFH effect. For example, as shown, A UFH concentration of 0.3 IU/ml would now be equal to an aPTT between 48-108 seconds. Thus, a target aPTT of 60-85 seconds could be sub-, supra-, or therapeutic. CAP/ACCP recommend an aPTT range which is individually calibrated for each specific reagent and instrument. Even with appropriate calibration and validation of aPTT range, it is a significant challenge to consistently maintain true therapeutic aPTT levels in the individual patient. ";
text10 = "Variability of aPTT by ReagentThis graph further demonstrates the tremendous difference in TPL sensitivity and UFH responsiveness with four different reagents. Each reagent produces a different aPTT at therapeutic UFH levels of between 0.2-0.4 IU/ml..";
text11 = "Medication ErrorsAnother concern with UFH is the high number of medication errors associated with its use. The 2001 MEDMARX data is shown in the tables on the slide, indicating that UFH is the number three drug involved in medication errors producing patient harm. Further UFH is one of the top drugs involved in patient fatalities. Thus, extreme care must be taken in dosing, administering, and monitoring UFH therapy. ";
text12 = "OutlineThe next part of the program addresses the comparative clinical evidence, consensus guidelines, and medication pathways of anticoagulants in acute coronary syndromes (UA/NSTEMI and STEMI).";
text13 = "Acute Coronary SyndromesThis graphic depicts the large numbers of hospital admissions for ACS each year, including UA/NSTEMI and STEMI patients.";
text14 = "ACS Spectrum As shown in the graphic, advancing atherosclerosis is the underlying cause of most acute coronary syndromes. Atherosclerotic plaques advance over time and stable angina develops. Unstable angina and NSTEMI are associated with inflammation in the artery as well as the development of fissures within the plaque and actual plaque rupture. As depicted, in unstable angina and NSTEMI, these changes result in a flow-limiting non-occlusive thrombus within the affected artery. In acute STEMI, the thrombus totally occludes the artery and damages the heart muscle if early reperfusion does not occur. Key clinical trials involving the use of UFH and other agents such as LMWHs in UA/NSTEMI, which have shaped recent practice ,are shown in the blue box. These trials will be discussed in some detail. ";
text15 = "Evidence for Heparin in ACSUFH has been evaluated in a number of randomized, placebo-controlled trials for the short-term stabilization of UA/NSTEMI. When given alone, UFH has been shown to be effective in preventing myocardial infarction and recurrent angina. When it is combined with aspirin, the results of clinical trials suggest that it reduces short-term rates of cardiovascular death and MI by ~30% compared with aspirin alone. Considering the actual risk reduction and confidence intervals however (as shown on the slide), the benefit is of borderline significance. ";
text16 = "UA/NSTEMI: UFH vs LMWHA number of randomized controlled clinical trials comparing LMWH to UFH have been conducted. Dalteparin (FRIC) has been studied in UA/NSTEMI and basically has been shown to be equivalent to UFH in preventing recurrent ischemic events. On the basis of the FRIC trial, dalteparin was FDA-approved for this indication. The TIMI 11B and ESSENCE trials, as shown on the slide, provide the best efficacy data for the use of LMWHs in the treatment of ACS (UA/NSTEMI). Both of these trials compared enoxaparin with UFH. The composite endpoints for these trials were death, MI, and urgent revascularization in TIMI 11B and death, MI, and recurrent angina in the ESSENCE trial. The odds ratios and confidence intervals for both trials show the superiority of enoxaparin vs. UFH. The ESSENCE trial demonstrated a significant reduction in the composite endpoint at 14 days, 30 days, and at one year, compared to UFH. In the short-term phase of the TIMI 11B trial, there was a significant reduction in the composite endpoint at 14 days compared to UFH. In the long-term treatment phase (enoxaparin treatment for 43 days), the composite endpoint was again reduced significantly compared to UFH. ";
text17 = "UFH Trial IssuesSeveral issues or questions have been raised regarding the ESSENCE and TIMI 11B trials and the superiority of enoxaparin over UFH. For example, in the TIMI 11 B trial, the question has been raised regarding the lack of therapeutic aPTTs with UFH in many patients. As shown in the graphic, Bozovich et al assessed aPTT levels with UFH in the trial and found that about 7% of patients were subtherapeutic with UFH, 47% were therapeutic, and 46% were supratherapeutic. Regardless of the aPTT level, the efficacy of enoxaparin was still superior to UFH. This evaluation also points out the difficulty of achieving therapeutic aPTTs with UFH.A second issue is that some of the components of the composite endpoints such as revascularization and recurrent angina have been referred to as \"soft\" endpoints. However, these are important pre-determined clinical outcomes which significantly impact economics. Finally, the comparative duration of therapy has been questioned. As shown, the average duration of enoxaparin in these trials was 2.6-4.4 days vs. 2.6-3.0 days with UFH.";
text18 = "Early Effect: D/MI/URThis slide compares the early treatment effect of UFH vs.enoxaparin in the ESSENCE and TIMI 11B trials. Even after 48 hours of therapy, there was an early divergence of event rates at 48 hours in these trials, favoring enoxaparin.";
text19 = "UA/NSTEMI: Meta-AnalysisThe results of a large meta analysis of ESSENCE and TIMI 11B (7,081 patients) are shown here. The treatment effect of enoxaparin vs. UFH on death and nonfatal MI at various time points are shown. The superior treatment effects of enoxaparin are seen early and are persistent. ";
text20 = "Rebound in ACSRebound ischemic events after the abrupt discontinuation of UFH have been demonstrated in UA/NSTEMI and in STEMI trials (GUSTO-I, GUSTO-IIb, ESSENCE). Possible mechanisms which have been proposed include: Platelet activation/aggregation effect of UFH outlives its therapeutic anticoagulation effect Thrombin activity is increased within 6 hours after discontinuationThus, a relative hypercoagulable state may exist after UFH withdrawal. Rebound events with other agents such as LMWHs are possible but appear to occur less frequestly. ";
text21 = "Heparin ReboundData from the GUSTO IIB trial is shown on the bar graph. On the y axis is the rate of reinfarction. The x axis is the time after stopping IV UFH. Clearly, there is a peak in ischemic events between 2-8 hours after stopping the drug. Thus, the possibility of UFH rebound ischemic events must be considered when using the drug. ";
text22 = "UA/NSTEMI: UFH +/- GPBWith the recognition that platelet activation and aggregation was an important contributor to thrombus formation in UA/NSTEMI patients, it was hypothesized that more potent platelet inhibition through the use of GPBs could further prevent acute ischemic events. In the setting of medical stabilization, UFH in combination with tirofiban in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs, and Symptoms (PRISM PLUS) trial and eptifibatide in the Unstable Angina Receptor Suppression Using Integrilin (PURSUIT) trial was shown to significantly reduce ischemic events at 30 days.The benefit of UFH in combination with GPBs in PCI/stent patients has been demonstrated. The Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial with abciximab/UFH demonstrated a 50% reduction in ischemic events at 30 days compared to a 35% reduction with eptifibatide/UFH in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrelin Therapy (ESPRIT) trial. ";
text23 = "INTERACT: (UFH vs. LMWH) + GPBRecognizing that GP IIb/IIa receptor blockers ( GPBs) play an important role in the treatment of high-risk ACS patients, several trials have now assessed the use and safety of combining GPBs with UFH vs, the LMWH enoxaparin. The INTERACT trial evaluated 746 high-risk UA/NSTEMI patients who were treated with the GPB eptifibatide. Patients were then randomized to either SC enoxaparin or IV UFH. The primary endpoint was major bleeding at 96 hours. Secondary efficacy endpoints were also assessed.The trial confirmed the difficulty of establishing early therapeutic aPTTs with UFH. Other key findings included:Less major bleeding at 96 hrs (0.6% enox vs. 4.6% UFH (p=0.03), fewer ischemic episodes ( 14.3% enox vs. 25.4% UFH (p=0.0002), and fewer 30-day deaths/Mis (5% enox vs 9% UFH (p=0.03) with enoxaparin. The results indicated that enoxaparin was at least as safe and effective if not better than UFH in combination with a GPB prior to cath/PCI";
text24 = "RESCUE ACS: (UFH vs. LMWH) + GPBThe RESCUE ACS trial is a large study which is further assessing the efficacy and safety of UFH vs. enoxaparin in combination with a GPB. The trial is enrolling 3,000 high-risk NSTE ACS patients with a TIMI risk score of > 4. The patients are randomized to SC enoxaparin or IV UFH for 48 hours or until the patient undergoes an interventional procedure. The primary endpoint is death/MI/recurrent angina requiring revascularizatiion at 30 days. ";
text25 = "NICE 3: LMWH + GPBAs shown, the NICE 3 trial assessed the use of enoxaparin alone and in combination with a GPB in ACS patients. The objectives if the NICE 3 study were: To assess the safety profile (primarily bleeding) of enoxaparin and a GP IIb.IIIa blocker (abciximab, eptifibatide, or tirofiban) in patients with ACS· To assess the feasibility and safety of bringing patients to the cath lab on combination therapy (without the use of UFH)A total of 661 ACS patients (NSTEMI) were randomized to enoxaparin alone, enoxaparin plus tirofiban, enoxaparin plus eptifibatide, or enoxaparin plus abciximab. The primary endpoint was non-CABG major bleeding during hospitalization. Secondary endpoints included clinical efficacy as the composite endpoint of death, MI, or ischemia-driven TVR and minor bleeding. If patients went to the cath lab, combination therapy continued and no UFH was used. If patients went within 8 hours of the last dose of enoxaparin, no additional enoxaparin was given. If more than 8 hours had elapsed since the last dose of enoxaparin, a dose of 0.3 mg/kg IV enoxaparin was given. The NICE 3 study results and implications were as follows: Combining enoxaparin with a GP IIb/IIIa blocker did not result in excess major bleeding Patients on combination therapy can safely undergo PCI Clinical outcomes were comparable to those noted in prior studies Thus, it is not necessary to use UFH in UA/NSTEMI patients undergoing PCI who are treated with enoxaparin and a GP IIb/IIIa blocker and logistical concerns about transition to the cath lab have been addressed The NICE 3 trial was an important foundation for future investigations ";
text26 = "SC LMWH During PCIThe Collet trial assessed the use of LMWH enoxaparin in the setting of PCI. Patients were transitioned to PCI within 8 hours of the a.m. SC dose of enoxaparin. The important findings and implications of this trial were: Anti Xa levels at time of PCI were 0.98 + 0.03 IU/ml and >0.5 IU/ml in 98% of patients No abrupt closures or urgent revascularizations post-PCI were reported Death/MI 3.0% in PCI group vs. 6.2% in whole group vs. 10.8% in non-cath group Major bleeding 0.8% in PCI group vs. 1.3% in non-cath group Preliminary evidence suggests: PCI within 8 hr of last SC enox dose is safe/effective ";
text27 = "SYNERGY: (UFH vs. LMWH) +/- GPBThe SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization & GlYcoprotein IIb/IIIa Inhibitors) trial was a prospective, randomized, open-label study evaluating the efficacy and safety of enoxaparin versus UFH in high-risk patients presenting with non-ST-elevation ACS and treated with an early invasive strategy. As shown in this figure, a total of 10,027 patients were randomly assigned to either enoxaparin SC (1 mg/kg) every 12 hours or unfractionated heparin (bolus 60 U/kg, then 12 U/kg/hour). The median age of the patients was 68, and 34% were female. Among patients receiving enoxaparin, catheterization could be performed at any time after the last dose. No additional enoxaparin was given if percutaneous coronary intervention (PCI) was performed less than eight hours since the last SC dose but an intravenous dose of 0.3 mg/kg was given when PCI was performed eight to 12 hours after the last dose. SYNERGY was conducted at 467 investigative sites in the United States, Canada, Europe and South America. It is the largest trial ever conducted in UA/NSTEMI. For inclusion, patients were required to have at least 2 of the following: age > 60, ST ? (transient) or ?, or (+) CK-MB or troponin. The primary endpoint of the trial was a composite of death/MI at 30 days.There was significant crossover between enoxaparin and UFH during the study, therefore the enrollment target was extended from 8,000 to 10,000 patients. Again, this trial was pivotal because it assessed the \"real-world\" use of SC enoxaparin in early transition to PCI without additional anticoagulation with UFH. ";
text28 = "SYNERGY: EfficacyThe results of The SYNERGY trial were presented at the 2004 Annual Scientific Session of the American College of Cardiology in New Orleans, Louisiana. As shown in left bar graph, enoxaparin was not shown to be superior to UFH, but did meet prespecified criteria for noninferiority. Thus, it was shown to be at least as effective as UFH in reducing the incidence of death/MI at 30 days in the treatment of high-risk patients with non-ST-elevation ACS undergoing an early invasive strategy (14.0 percent enoxaparin vs. 14.5 percent UFH, p= NS). There also was no difference in death alone, myocardial infarction alone, or in stroke rates. In both groups, 92% of patients went to the catheterization lab during their baseline hospitalization (median time was about 21.5 hours from randomization). The average time to PCI was 23 hours for enoxaparin (6-49 hrs) vs. 22 hours (6-48 hrs) for UFH. Fifty-six percent of the enoxaparin group and 58% of the heparin group were also given a GPB.As shown on the bar graph to the right, patients receiving enoxaparin throughout the course of therapy (no crossover) did experience superior outcomes compared to UFH. A prespecified secondary analysis of 5,637 patients enrolled in SYNERGY showed that those who began treatment with enoxaparin prior to randomization and continued on it throughout the course of therapy experienced an 18 percent relative risk reduction in the incidence of death and myocardial infarction at 30 days vs. patients who were started and continued on UFH (12.8% vs. 15.6%, p=0.0029). These findings indicate that switching anticoagulant agents during an episode of ACS, including in the catheterization lab, provides no clinical benefit and potentially increases bleeding complications.";
text29 = "Bleeding EventsSafety endpoints evaluated in SYNERGY included bleeding indices (GUSTO and TIMI major bleeding criteria), incidence of transfusions, and intracranial hemorrhage (ICH).For the entire population: There was a non-significant difference in GUSTO severe events in the enoxaparin group (2.9 vs. 2.4) For non-CABG TIMI major bleeding events, there was a statistically significant increase in the enoxaparin group (2.4 vs. 1.7) There were no differences observed in the incidence of blood transfusions or ICH.It is important to note that TIMI criteria for major bleeding is broader than GUSTO severe bleeding criteria. The clinical relevance of TIMI major bleeding is less than the clinical relevance of GUSTO severe bleeding. To put this into perspective, the number of patients needed to treat with enoxaparin to observe one additional non-CABG-related major bleed per the TIMI criteria is estimated to be 200 patients. Though not a primary safety endpoint, it is important to note there were also no differences in the incidence of stroke between the two groups";
text30 = "Thrombotic ComplicationsA total of 2,321 patients randomized to enoxaparin and 2,364 patients randomized to UFH underwent PCI.There was no difference between the two treatment groups in the rate of unsuccessful PCI, threatened abrupt closure, abrupt closure or emergency CABGRecall that part of the rationale of SYNERGY was to investigate if patients receiving enoxaparin could safely brought to catheterization.";
text31 = "ACC/AHA 2002 Practice GuidelinesAs evidence evolves, practice guidelines evolve. If we look at the current practice guidelines of the ACC/AHA (March 2002) in the area of anticoagulation therapy in UA/NSTEMI there have been some significant recent changes.It is recommended that anticoagulation with SC LMWH or IV UFH should be added to antiplatelet therapy with ASA and/or clopidogrel. The level of evidence is A (the highest level) and it is a Class I guideline indicating that the intervention is useful and effective. The second part of the guideline represents the most important change in that now enoxaparin is recommended as the anticoagulant of choice in such patients as a class IIa guideline with an A level of evidence. This indicates that the weight of evidence is in favor of enhanced efficacy with enoxaparin. This change reflects the evidene from key trials such as theTIMI 11B and ESSENCE trials. These guidelines can be accessed on either the ACC or AHA websites. ";
text32 = "UA/NSTEMI PathwayEvidence also defines the medication components of the UA/NSTEMI pathway. As shown, the medication section of the pathway should include IV NTG, a beta blocker, and aspirin 81-160 mg stat and then daily thereafter. Clopidogrel is now recognized as a standard of care in these patients. Because of the superiority of enoxaparin in medically stabilizing UA patients (ESSENCE , TIMI 11B trials), it is listed as an agent of choice on the pathway. UFH would be an alternative. Tirofiban (or eptifibatide as another GPB alternative) is listed with a question mark because of the controversy regarding their actual effectiveness for medical stabilization, depending on the risk level of the patient. Finally, a statin and an ACEI represent standards of care today on this pathway.";
text33 = "ACS Spectrum As introduced earlier, this graphic depicts the underlying pathophysiooogy of ACS. The next segment of the program focuses on key clinical trials in STEMI where there is complete occlusion of the infarct-related artery. These include the ASSENT-3, ASSENT-3 PLUS, and the ExTRACT trials. In terms of anticogulation, these trials compare UFH vs. enoxaparin in combination with fibrinolytic therapy in the form of tenecteplase (TNK). ";
text34 = "Combination RationaleThe primary rationale for using combination antithrombotic therapy in STEMI is to decrease the formation of thrombus in the infarct-related artery. The hypothesis was that combining antithrombotics with different mechanisms and sites of action would significantly decrease the thrombus burden. As shown in Phase II angiographic trials, much of the benefit of combination therapy was predicted to be secondary to an improvement in epicardial and microvascular coronary blood flow. Arteries were opened earlier, and blood flow was increased compared with a fibrinolytic alone. Other benefits of combination therapy may include a reduction in reinfarction and facilitation of PCI. ";
text35 = "ASSENT-3The ASSENT-3 trial compared the safety and efficacy of a TNK/abciximab combination with heparin and a full-dose TNK/enoxaparin combination with a standard arm of full-dose TNK plus heparin in STEMI.Six thousand patients with STEMI received aspirin (150 to 325 mg daily) and were then randomized to 1 of 3 treatment arms: TNK (0.53-mg/kg bolus) plus heparin (60-U/kg bolus, 12-U/kg/h ´ 12 hours); TNK (0.27-mg/kg bolus) plus abciximab (0.25-mg/kg bolus, 0.125-?g/kg/min ´ 12 hours) and heparin (40-U/kg bolus, 7-U/kg/h infusion); or TNK (0.53 mg/kg) plus enoxaparin (15-mg IV bolus, 1 mg/kg subcutaneous injection every 12 hours).Primary endpoints included the composite outcome of death, reinfarction, and refractory ischemia at 30 days and major bleeding. Shown here on the bar graph to the left, are the results of the primary endpoint of death, MI, or refractory ischemia at 30 days. After correcting for multiple testing (Bonferroni), a statistically significant reduction in ischemic events was demonstrated for the primary efficacy endpoint when the enoxaparin group was compared to the unfractionated heparin group (standard arm) (p=0.0009) and when the abciximab group was compared to the unfractionated heparin group (p=0.0002).As shown in the bar graph to the right, significantly more major bleeding complications (p=0.0002), were seen in the abciximab group compared with the unfractionated heparin group.There was no significant difference (NS) in major bleeding in the enoxaparin group compared to the UFH group.";
text36 = "UFH vs. LMWH in STEMIA recent meta-analysis of 6 studies in STEMI assessed the clinical outcomes of UFH (control) vs. enoxaparin in combination with a fibrinolytic. As shown on the whisker plots (RRR and confidence intervals), consistent with the ASSENT-3 results, enoxaparin was shown to be superior to UFH. ";
text37 = "ASSENT-3 PLUSThe ASSENT-3 Plus trial was designed to evaluate the prehospital administration of TNK plus the LMWH enoxaparin. The comparison arm was TNK plus heparin. The trial included 1,639 patients with STEMI who were randomly assigned to receive TNK/enoxaparin (enoxaparin 30 mg IV bolus, then TNK bolus followed by SC enoxaparin every 12 hours up to 7 days) or TNK/heparin (UFH IV bolus followed immediately by TNK bolus, then IV infusion of UFH for up to 48 hours).The primary endpoints were the composites of death/MI/refractory ischemia and death/MI/refractory ischemia/ICH/major bleed. Compared to the in-hospital ASSENT-3 trial, prehospital fibrinolysis in the ASSENT-3 Plus trial reduced the delay in treatment by about 45 nimutes.As shown in the bar graphs, the TNK/enoxaparin combination reduced both endpoints compared to TNK/heparin, although the reductions did not reach statistical significance. There was an increase in ICH reported in elderly patients (> 75 years of age) with the TNK/enoxaparin combination, Thus, ongoing trials will define the most appropriate dose of enoxaparin to use in the elderly in this setting";
text38 = "ExTRACT- TIMI 25The ExTRACT (TIMI 25) trial is a large (n ~20,000) ongoing study which is assessing the efficacy and safety of enoxaparin in STEMI. As shown, all patients will be treated with ASA and a fibrinolytic of choice. They will be randomized to enoxaparin or IV UFH. The primary endpoint is death/MI at 30 days. As noted on the slide, the dose of enoxaparin will be reduced in patients > 75 years old. No bolus dose will be given to these patients and the SC dose will be reduced to 75% of the usual SC dose (0.75 mg/kg every 12 hours). Patients enrollment is underway.";
text39 = "GRACE Registry The GRACE registry is a very large database of ACS patients. One of the key outcomes assessed within this registry has been hospital outcomes in ACS patients who have received UFH vs. LMWH. It is noteworthy that LMWH was associated with better outcomes in mortality, major bleeding, stroke rates, and reinfarction compared to UFH (all statistically significant).";
text40 = "Medication UtilizationThe use of adjunctive medications in MI patients is primarily aimed at reducing the occurrence of future cardiac events. There is considerable evidence that they significantly reduce such events. The use of these adjunctive strategies has increased significantly over the past 5 years. The National Registry of Myocardial Infarction (NRMI), initiated by Genentech, Inc.in 1990, is an observational study utilizing cross-sectional observational databases for collecting presentation, treatment, and outcome data on patients with AMI. Since 1990, data from over 2,000,000 patients experiencing MI have been collected from over 1,500 institutions. These data have been used by participating hospitals to improve patient care through the evaluation and assessment of their delivery of care. \"Like\" hospital, state, and national data (data from institutions that have similar organizations or demographics) provide extensive benchmarking of trends in MI practice. The current data from NRMI 4 (June 2002-July 2003) is reflected on the graph. As shown, a fibrinolytic was used in approximately one-third of patients. A glycoprotein blocker was used in ~23% of patients. As expected, the use of early aspirin therapy has increased to beyond 90% of patients. Beta blocker usage now exceeds 80%. The early use of ACE inhibitors has increased to about 50%, still reflecting underutilization. As already mentioned, the HOPE trial provides new evidence of the benefit of ACEIs in all patients with atherosclerotic disease. The remainder of the graph shows that LMWH is now overtaking UFH as the anticoagulant of choice in this setting. Statins are clearly underutilized considering the improved outcomes which have been demonstrated in secondary prevention (4S, LIPID, CARE trials) as well as in more recent trials (PROVE-IT, REVERSAL) employing aggressive use of these agents.";
text41 = "STEMI Medication PathwayIn assessing therapy for inclusion within a STEMI medication pathway (alternative to primary PCI), new agents, evidence, and regimens must continually be evaluated and compared to current agents or regimens. A fibrinolytic protocol which reflects the most current evidence and best available agent is included. Also, as shown on the medication pathway, aspirin should be initiated immediately in the emergency department and continued at a dose of 81-325 mg daily. Enoxaparin is listed as the anticoagulant of choice because of its superior evidence as part of STEMI combination therapy. Beta blockers and ACEIs should be incorporated on the medication pathway as a standard of care in STEMI patients. Finally, instituting a \"statin\" should be strongly considered during the hospital stay to aggressively reduce cholesterol concentrations and for their anti-inflammatory effects. The National Cholesterol Education Program recommends that LDL cholesterol be reduced to 90 kg) and in the treatment of unstable angina/NSTEMI patients (10,000 units/dose, >83 kg, as per manufacturer). UFH remains a possible alternative in risk patients such as the morbidly obese.";
text45 = "Renal Dosing: EnoxaparinThe dosing of LMWHs such as enoxaparin in renal impairment has not been well defined in the past. However, recently specific dosing guidelines for enoxaparin in renally impaired patients (creatinine clearance