Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel. BACKGROUND: The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined. METHODS: We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use. RESULTS: Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj) 0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (p(interaction) = 0.61). CONCLUSIONS: In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI.     

A strategy of using enoxaparin as adjunctive antithrombin therapy reduces death and recurrent myocardial infarction in patients who achieve early ST-segment resolution after fibrinolytic therapy: the ExTRACT-TIMI 25 ECG study.

AIMS: To determine the relationship between a strategy of enoxaparin (ENOX), early ST-segment resolution (STRes), and clinical outcomes on patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolysis. METHODS AND RESULTS: Baseline and 180 min ECGs were analysed in 3208 of the 20 479 patients in the ExTRACT-TIMI 25 trial, which randomifzed patients with STEMI to ENOX vs. unfractionated heparin (UFH) as adjunctive therapy. STRes was defined as complete (70%), partial (30-70%), or none (<30%). There was no evidence for a difference in STRes between the groups assigned to the ENOX or UFH (median 69.4 vs. 67.2%; P = 0.13). Among patients with complete STRes (n = 1100), ENOX significantly reduced death or non-fatal recurrent MI at 30 days when compared with UFH (4.4 vs. 9.9%; OR(adj) 0.39; P < 0.001), whereas there was no difference in patients with only partial or no STRes [14.2 vs. 12.5%; OR(adj) 1.0; P = 0.98 (n = 368) and 16.2 vs. 15.9%; OR(adj) 1.0; P = 0.97 (n = 830), P for interaction = 0.008]. CONCLUSION: When compared with UFH, a strategy of ENOX significantly reduces death or non-fatal recurrent MI in patients who achieved complete STRes, but not in patients with less STRes. These data suggest that a strategy of ENOX improves outcomes by preventing re-occlusion in patients achieving initial successful reperfusion after fibrinolytic therapy rather than by facilitating initial reperfusion.     

The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial.

OBJECTIVES: The ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial provided the opportunity to evaluate the impact of renal dysfunction on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and compare enoxaparin (ENOX) and unfractionated heparin (UFH). BACKGROUND: It is unclear how renal dysfunction influences the balance between benefit and risk of antithrombotic therapy. METHODS: In the ExTRACT-TIMI 25 trial, 20,479 patients were randomized to UFH or ENOX. A reduced ENOX dose was administered to patients age > or =75 years and those with an estimated creatinine clearance (CrCl) <30 ml/min. RESULTS: A powerful relationship was observed between the severity of renal dysfunction (per 10 ml/min decrement in CrCl) and death, stroke, intracranial hemorrhage, and major and minor bleeding (p < 0.001 for each). There was a progressive increase in the treatment benefit with ENOX on death or nonfatal myocardial infarction (p < 0.01) with better renal function. Net clinical benefit (death, nonfatal MI, or nonfatal major bleeding) was significantly superior with ENOX (p < 0.001) for patients with a CrCl >60 ml/min (79.1% of the study population). Major bleeding and intracranial hemorrhage did not differ for patients with preserved renal function (CrCl >90 ml/min), but in those with renal dysfunction there was a progressively greater increase in the risk of major and minor bleeding with ENOX. CONCLUSIONS: Enoxaparin was superior to UFH for the majority of subjects. With more severe renal dysfunction, the net clinical benefit between ENOX and UFH did not differ, despite the rise in adverse events in both treatment groups. Future studies should take renal dysfunction into account when assessing antithrombotic regimens.     

Safety and effectiveness of enoxaparin following fibrinolytic therapy: Results of the Acute Myocardial Infarction (AMI)-QUEBEC registry

BACKGROUND:

Previous randomized controlled trials and meta-analyses demonstrated the superior efficacy of enoxaparin (ENOX) over unfractionated heparin (UFH) in patients with ST segment elevation myocardial infarction (STEMI). The external validity of randomized controlled trials may be limited by selective inclusion of patients who are younger and healthier than the ‘real-life’ population.

OBJECTIVE:

To evaluate the safety and effectiveness of ENOX compared with UFH in unselected STEMI patients.

METHODS:

The safety and effectiveness of ENOX and UFH were compared in STEMI patients who received fibrinolytic therapy at 17 Quebec hospitals in 2003.

RESULTS:

A total of 498 STEMI patients received systemic anticoagulation, with ENOX and UFH administered in 114 and 384 patients, respectively. There were no differences in baseline characteristics between the two patient groups. The rates of in-hospital major adverse cardiac or cerebral events were 11.4% in the ENOX group compared with 14.0% in the UFH group (P=0.51). In-hospital death or nonfatal reinfarction occurred in 7.9% of patients who received ENOX compared with 9.9% of patients who received UFH (P=0.52). Major bleeding occurred in 4.4% of patients who received ENOX versus 6.0% in patients who received UFH (P=0.51).

INTERPRETATION:

There was no significant difference in the rates of in-hospital adverse events in the ENOX group compared with the UFH group, when used in the real-life context. Larger observational studies may further confirm the safety, effectiveness and optimal duration of the administration of ENOX in unselected STEMI patients treated with fibrinolysis.     

Comparison of enoxaparin versus unfractionated heparin in patients with unstable angina pectoris/non-ST-segment elevation acute myocardial infarction having subsequent percutaneous coronary intervention

Patients with unstable angina or non-ST-segment elevation myocardial infarction (MI) may undergo invasive revascularization procedures shortly after admission to hospital or after a brief period of stabilization. In the Thrombolysis In Myocardial Infarction (TIMI) 11B trial and Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial 1,326 patients underwent percutaneous coronary intervention (PCI). A total of 924 patients underwent PCI during the initial hospitalization period, and of these, 445 patients did so while receiving treatment with unfractionated heparin (UFH) or the low-molecular-weight heparin, enoxaparin. This analysis compared efficacy and clinical events in the enoxaparin and UFH groups in patients who: (1) underwent PCI while on treatment versus those who did not, and (2) underwent PCI in hospital. We also compared those who did not undergo PCI. Treatment with enoxaparin (1 mg/kg given as twice daily subcutaneous injections) was beneficial and well tolerated in patients with unstable angina and non-ST-segment elevation MI who underwent PCI. Compared with UFH, enoxaparin significantly reduced the likelihood of clinical events (death and nonfatal MI after PCI) in patients who underwent PCI after 1 year (p = 0.003 for in-hospital PCI; p = 0.005 for on-treatment PCI), with a trend toward a reduced event rate at 43 days. In addition, patients treated with enoxaparin who did not undergo PCI also showed a reduction in the risk of death, nonfatal MI, and urgent revascularization when compared with those treated with UFH (significant at 43 days, with a trend persisting at 1 year). Study limitations were that PCI was nonrandomized, the analysis was post hoc, and the sample size was relatively small. Nevertheless, in the absence of large clinical trials, this study suggests that treatment with enoxaparin was well tolerated, and exhibited a similar risk of major hemorrhage to UFH in patients who underwent PCI.     

Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We sought to determine if an underlying mechanism of the association between prolonged symptom-to-treatment times and adverse outcomes may be an association of symptom-to-treatment times with impaired Thrombolysis In Myocardial Infarction myocardial perfusion grades (TMPGs). BACKGROUND: Prolonged symptom duration among ST-segment elevation myocardial infarction (STEMI) patients undergoing fibrinolytic therapy is associated with adverse outcomes. METHODS: Angiography was performed 60 min after fibrinolytic administration in 3,845 Thrombolysis In Myocardial Infarction (TIMI) trial patients. RESULTS: The median time from symptom onset to treatment was longer among patients with impaired myocardial perfusion (3.0 h for TMPG 0/1 vs. 2.7 h for TMPG 2/3; p = 0.001). In a multivariate model, impaired tissue perfusion (TMPG 0/1) remained associated with increased time to treatment (odds ratio 1.14 per hour of delay; p = 0.007) even after adjusting for Thrombolysis In Myocardial Infarction flow grade (TFG) 3, left anterior descending infarct location, and baseline clinical characteristics. Impaired myocardial perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) was associated with longer median times to treatment (3.0 h for TMPG 2/3 vs. 2.7 h for TMPG 0/1; p = 0.017), as was abnormal epicardial flow after rescue/adjunctive PCI (3.3 h for TFG 0/1/2 vs. 2.8 h for TFG 3; p = 0.005). Thirty-day mortality was associated with longer time from onset of symptoms to treatment (6.6% mortality for time to treatment >4 h vs. 3.3%; p < 0.001), even among patients undergoing rescue PCI. CONCLUSIONS: A prolonged symptom to treatment time among STEMI patients is associated with impaired myocardial perfusion independent of epicardial flow both immediately after fibrinolytic administration and after rescue/adjunctive PCI. These data provide a pathophysiologic link between prolonged symptoms due to vessel occlusion, impaired myocardial perfusion, and poor clinical outcomes.     

Association of a negative residual stenosis following rescue/adjunctive percutaneous coronary intervention with impaired myocardial perfusion and adverse outcomes among ST-segment elevation myocardial infarction patients

OBJECTIVES: We hypothesized that <0% residual stenosis (RS) after rescue/adjunctive percutaneous coronary intervention (PCI) following fibrinolytic administration in ST-segment elevation myocardial infarction (STEMI) would be associated with improved outcomes. BACKGROUND: Prior studies have associated larger lumen diameters after PCI with reduced rates of restenosis and target vessel revascularization. METHODS: Data were drawn from 748 patients with open epicardial arteries and with optimal luminal results (RS <20%) following rescue/adjunctive PCI after fibrinolytic administration in six STEMI trials. Patients were divided into two groups: 1) <0% RS and 2) 0% to 20% RS. RESULTS: A RS <0% was associated with greater gains in lumen diameter and smaller reference diameters after PCI (p < 0.001 for each), with a trend toward less frequent Thrombolysis In Myocardial Infarction flow grade (TFG) 3. A RS <0% was associated with a greater incidence of abnormal post-PCI Thrombolysis In Myocardial Infarction myocardial perfusion grades (TMPGs) (odds ratio 2.6 [1.2 to 5.9] for TMPG 0/1/2, p = 0.02), even when the analysis was restricted to patients with post-PCI TFG 3. CONCLUSIONS: A RS <0% following rescue/adjunctive PCI after fibrinolytic therapy for STEMI was independently associated with a reduction in the frequency of normal myocardial perfusion. Potential mechanisms of this finding include greater downstream embolization, increased stimulation of arterial stretch receptors with resultant coronary vasoconstriction, and increased vessel-wall injury after PCI. These findings suggest that additional prospective studies are needed to assess optimal RS that minimizes long-term restenosis without adverse effects.     

Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis.

AIMS: We compared outcomes of ST-elevation myocardial infarction (STEMI) patients randomized to a strategy of either enoxaparin or unfractionated heparin (UFH) to support fibrinolysis. METHODS AND RESULTS: In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction Study 25 (ExTRACT-TIMI 25) trial, 20,479 patients undergoing fibrinolysis for STEMI with a fibrin-specific agent (N = 16,283) or streptokinase (SK) (N = 4139) were randomized to enoxaparin throughout their hospitalization or UFH for at least 48 h. The primary end point of death or nonfatal recurrent MI through 30 days occurred in 12.0% of patients in the UFH and 9.8% in the enoxaparin groups when treated with fibrin-specific lytics [odds ratio(adjusted) (OR(adj)) 0.78; 95% CI 0.70-0.87; P < 0.001] and 11.8 vs. 10.2%, respectively, when treated with SK (OR(adj) 0.83; 95% CI 0.66-1.04; P = 0.10; P(interaction) = 0.58). Major bleeding rates including intracranial hemorrhage within the fibrin-specific cohort were 1.2 and 2.0% in the UFH and enoxaparin groups, respectively (P < 0.001) and 2.0% in UFH and 2.4% in enoxaparin patients in the SK cohort (P = 0.16). Interaction tests between antithrombin- and lytic-type were non-significant (P = 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (OR(adj) 0.82; 95% CI 0.74-0.91; P < 0.001) and favoured enoxaparin in the SK cohort (OR(adj) 0.89; 95% CI 0.72-1.10; P = 0.29; P(interaction) = 0.53). CONCLUSION: The benefits of an enoxaparin strategy over UFH were observed in both SK and fibrin-specific-treated STEMI patients. Therefore, an enoxaparin strategy is preferred over UFH to support fibrinolysis for STEMI regardless of lytic agent.     

The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial

OBJECTIVES: The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI) study were to demonstrate that enoxaparin was superior to unfractionated heparin (UFH) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infarction (STEMI) who do not receive timely reperfusion. BACKGROUND: An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion. METHODS: A total of 1224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002. Patients with STEMI ineligible for reperfusion were randomized to enoxaparin, enoxaparin plus tirofiban, UFH, or UFH plus tirofiban. All patients received oral aspirin. The primary efficacy end point was the 30-day combined incidence of death, reinfarction, or recurrent angina; the primary analysis was the comparison of the pooled enoxaparin and UFH groups. REULTS: The incidence of the primary efficacy end point was 15.7% enoxaparin versus 17.3% for UFH (odds ratio 0.89 [95% confidence interval CI = 0.66 to 1.21]) and 16.6% for tirofiban versus 16.4% for placebo (odds ratio 1.02 [95% CI 0.75 to 1.38]). The Thrombolysis In Myocardial Infarction (TIMI) major hemorrhage rate was 1.5% for enoxaparin versus 1.3% for UFH (odds ratio 1.16 [95% CI 0.44 to 3.02]) and 1.8% versus 1% for tirofiban versus placebo (odds ratio 1.82 [95% CI 0.67 to 4.95]). CONCLUSIONS: This study did not show that enoxaparin significantly reduced the 30-day incidence of death, reinfarction, and recurrent angina compared with UFH in non-reperfused STEMI patients. However, enoxaparin appears to have a similar safety and efficacy profile to UFH and may be an alternative treatment. Additional therapy with tirofiban did not appear beneficial.     

Comparative early and late outcomes after primary percutaneous coronary intervention in ST-segment elevation and non-ST-segment elevation acute myocardial infarction (from the CADILLAC trial)

We determined the outcomes of patients with acute ST-segment elevation (STE) myocardial infarction (STEMI) and non-STEMI (NSTEMI) after primary percutaneous coronary intervention (PCI). The prognosis after primary PCI in STEMI has been extensively studied and defined. Outcomes of patients who undergo primary PCI for NSTEMI are less well established. In total, 2,082 patients with ongoing chest pain for > 30 minutes consistent with acute MI were randomized to balloon angioplasty versus stenting, each with/without abciximab. Of 1,964 patients, STEMI was present in 1,725 (87.8%) and NSTEMI in 239 (12.2%). Compared with STEMI, those with NSTEMI were more likely to have delayed time-to-hospital arrival (2.4 vs 1.8 hours, p = 0.0002) and increased door-to-balloon time (3.2 vs 1.9 hours, p < 0.0001). Patients with NSTEMI were more likely to have Thrombolysis In Myocardial Infarction grade 3 flow at baseline (37.3% vs 19.4%, p < 0.0001) and higher ejection fraction (58.7% vs 55.8%, p = 0.001), but similar rates of postprocedural Thrombolysis In Myocardial Infarction grade 3 flow. At 1 year, patients with NTEMI had similar mortality (3.4% vs 4.4%, p = 0.40) but higher rates of major adverse cardiac events (24.0% vs 16.6%, p = 0.007) that was driven by more frequent ischemic target vessel revascularization (21.8% vs 11.9%, p <0.0001). In conclusion, patients with acute MI without STE who are treated with primary PCI have marked delays to treatment, similar late mortality, and increased rates of ischemic target vessel revascularization compared with patients with STEMI, despite more favorable angiographic features at presentation and similar reperfusion success. The adverse prognosis of patients with NSTEMI should be recognized and efforts made to decrease reperfusion times.     

Outcome of urgent and elective percutaneous coronary interventions after pharmacologic reperfusion with tenecteplase combined with unfractionated heparin, enoxaparin, or abciximab

OBJECTIVES: The aim of this study was to evaluate percutaneous coronary intervention (PCI) in the Assessment of the Safety and Efficacy of New Thrombolytic Regimens (ASSENT-3) trial. BACKGROUND: In the ASSENT-3 trial, co-therapy with abciximab (ABC) or enoxaparin (ENOX) reduced ischemic complications after ST-elevation acute myocardial infarction treated with tenecteplase when compared with unfractionated heparin (UFH). The effect of these new co-therapies on the results of PCI is unknown. METHODS: Clinical outcomes in patients who received co-therapy with ABC, ENOX, or UFH and subsequently underwent an elective (n = 1,064) or urgent (n = 716) PCI in the ASSENT-3 trial were compared. RESULTS: No significant differences in clinical end points were observed in patients who underwent an elective PCI. A non-significant trend toward fewer in-hospital myocardial re-infarctions was seen with ABC and ENOX when compared with UFH (0.5% vs. 0.6% vs. 1.5%, respectively). The incidence of bleeding complications was similar in the three treatment arms. Significantly fewer ABC- and ENOX-treated patients needed urgent PCI compared with UFH (9.1% vs. 11.9% vs. 14.3%; p < 0.0001), but outcomes in these patients were in general less favorable (30-day mortality: 8.2% vs. 5.4% vs. 4.5%; 1-year mortality: 11.0% vs. 8.5% vs. 5.6%; in-hospital re-infarction: 3.9% vs. 2.5% vs. 2.7%; major bleeding complications: 8.8% vs. 7.0% vs. 3.4%). In pairwise comparisons with UFH, the higher one-year mortality and major bleeding rates after ABC were statistically significant (p = 0.045 and p = 0.012, respectively). CONCLUSIONS: Clinical outcomes after elective PCI were similar with the three antithrombotic co-therapies studied in ASSENT-3. Although fewer patients needed urgent PCI with ABC and ENOX, clinical outcomes were less favorable in this selected population, especially with ABC.     

Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial.

OBJECTIVES: We examined the utility of early percutaneous coronary intervention (PCI) in a trial that encouraged its use after thrombolysis and glycoprotein IIb/IIIa inhibition for acute myocardial infarction (MI). BACKGROUND: Early PCI has shown no benefit when performed early after thrombolysis alone. METHODS: We studied 323 patients (61%) who underwent PCI with planned initial angiography, at a median 63 min after reperfusion therapy began. A blinded core laboratory reviewed cineangiograms. Ischemic events, bleeding, angiographic results, and clinical outcomes were compared between early PCI and no-PCI patients (n = 162), between patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 before PCI versus flow grade 2 or 3, and among three treatment regimens. RESULTS: Early PCI patients showed a procedural success (<50% residual stenosis and TIMI flow grade 3) rate of 88% and a 30-day composite incidence of death, reinfarction, or urgent revascularization of 5.6%. These patients had fewer ischemic events and bleeding complications (15%) than did patients not undergoing early PCI (30%, p = 0.001). Early PCI was used more often in patients with initial TIMI flow grade 0 or 1 versus flow grade 2 or 3 (83% vs. 60%, p < 0.0001). Patients receiving abciximab with reduced-dose reteplase (5 U double bolus) showed an 86% incidence of TIMI grade 3 flow at approximately 90 min and a trend toward improved outcomes. CONCLUSIONS: In this analysis, early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective. This approach has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.     

Relation of hyperemic epicardial flow to outcomes among patients with ST-segment elevation myocardial infarction receiving fibrinolytic therapy

In patients with ST-segment elevation myocardial infarction (STEMI), the restoration of normal epicardial flow following fibrinolytic administration is associated with improved clinical outcomes. The goal of this analysis was to examine the relation between hyperemic flow and outcomes following fibrinolytic administration for STEMI. In Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28), patients with STEMI (n=3,491) treated with fibrinolytic therapy were scheduled to undergo angiography 48 to 192 hours after randomization. Corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) were assessed, and their associations with outcomes at 30 days were evaluated. When evaluating initial angiography of the infarct-related artery, there was a nearly linear relation between CTFC and 30-day mortality, with faster flow (lower CTFC) associated with improved outcomes. Conversely, in patients who underwent percutaneous coronary intervention (PCI), very fast flow (CTFC<14) after intervention was associated with worse outcomes. Post-PCI hyperemic flow (CTFC<14) was associated with a higher incidence of mortality (p=0.056), recurrent myocardial infarction (p=0.011), and a composite of death or myocardial infarction (p<0.001) compared with normal flow (CTFC 14 to 28). When post-PCI CTFC was further stratified by TMPG, there was a U-shaped relation between mortality and CTFC in patients with poor myocardial perfusion (TMPG 0 or 1). This relation appeared to be linear in patients with TMPG 2 or 3. In conclusion, in patients who undergo PCI after fibrinolytic therapy for STEMI, hyperemic flow on coronary angiography is associated with an increased incidence of adverse outcomes. Hyperemic flow with associated impaired myocardial perfusion may be a marker of more extensive downstream microembolization.     

Angiographic perfusion score in patients treated with PCI at late angiography following fibrinolytic administration for ST-segment elevation myocardial infarction is associated with morbidity and mortality at 30 days

Background  Among patients with ST-segment elevation myocardial infarction (STEMI), evidence of restoration of both normal epicardial arterial flow and myocardial perfusion early after the administration of fibrinolytic agents has been associated with improved clinical outcomes. In STEMI patients treated with fibrinolytic therapy and scheduled for angiography later during hospital admission, however, the association of later indices of flow and perfusion with clinical outcomes has not been assessed. Methods  Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 enrolled 3,491 STEMI patients treated with fibrinolytic therapy. Angiography was scheduled 48–192 h (median 84) after randomization. The Angiographic Perfusion Score (APS) (the sum of the TIMI Flow Grade and Myocardial Perfusion Grade before and after percutaneous coronary intervention (PCI), range of 0–12) was assessed in the 1,460 patients treated with PCI at late angiography, and its association with morbidity and mortality at 30 days was examined. Results  Full perfusion, defined as an APS of 10–12, was associated with the lowest mortality (0.8%), while partial perfusion (APS 4–9) (2.3%) and failed perfusion (APS 0–3) (18.0%) were associated with a higher incidence of mortality at 30 days (P < 0.001 for full perfusion vs. partial perfusion, P < 0.0001 for overall trend). In addition, full perfusion was associated with a lower incidence of recurrent myocardial infarction (MI), a composite of death and MI, recurrent myocardial ischemia, ventricular tachyarrhythmia, congestive heart failure and shock (P < 0.05 for all trends). Conclusion  Among STEMI patients treated with late PCI following fibrinolytic therapy, higher APS is associated with reduced morbidity and mortality.     

Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis.

AIMS: To determine whether the low-molecular weight heparin enoxaparin remains favourable when compared with unfractionated heparin (UFH) among patients with acute coronary syndromes (ACS) when incorporating efficacy and safety of these adjunctive therapies using a net clinical endpoint. METHODS AND RESULTS: We performed a meta-analysis of randomized trials of enoxaparin vs. UFH in ST-elevation-MI (STEMI) or non-ST-elevation-ACS (NSTEACS) (n = 49,088 patients in 12 trials). The net clinical endpoint was defined as death, MI, or major bleeding by 30 days. Death or myocardial infarction (MI) was significantly reduced with enoxaparin when compared with UFH (9.8 vs. 11.4%, OR 0.84, P < 0.001). The net clinical endpoint occurred less frequently with enoxaparin than UFH (12.5 vs. 13.5%, OR 0.90, P = 0.051). Major bleeding was higher with enoxaparin (4.3 vs. 3.4%, OR 1.25, P = 0.019). Among STEMI trials, the net clinical endpoint was significantly lower with enoxaparin (OR 0.84, P = 0.015), but there was no difference in NSTEACS trials (OR 0.97). CONCLUSIONS: When compared with UFH, enoxaparin was associated with superior efficacy as adjunctive antithrombin therapy among >49 000 patients across the ACS spectrum. Although bleeding was increased with enoxaparin, this increase was offset by a reduction in death or MI. The net clinical benefit in favour of enoxaparin was evident among the STEMI population and was neutral among the NSTEACS population.     

Angiographic and clinical outcomes in elderly subjects treated with percutaneous coronary intervention following fibrinolytic administration for ST-elevation myocardial infarction

Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) patients. The association of patient age with angiographic characteristics of flow and perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) following the administration of fibrinolytic therapy has not been previously investigated. Objectives and Methods We examined the association between age (≥70 years or < 70years) and clinical and angiographic outcomes in 1472 STEMI patients who underwent rescue/adjunctive PCI following fibrinolytic therapy in 7 TIMI trials. We hypothesized that elderly patients would have slower post-PCI epicardial flow and worsened outcomes compared to younger patients. Results The 218 patients aged≥70 years (14.8%) had more comorbidities than younger patients. Although these patients had significant angiographic improvement in TTMI frame counts and rates of TIMI Grade 3 flow following rescue/adjunctive PCI, elderly patients had higher (slower) post-PCI TTMI frame counts compared to the younger cohort (25 vs 22 frames, P = 0.039) , and less often achieved post-PCI TTMI Grade 3 flow (80.1 vs 86.4% , P = 0.017). The association between age (≥70 years) and slower post-PCI flow was independent of gender, time to treatment, left anterior descending (LAD) lesion location, and pulse and blood pressure on admission. Elderly patients also had 4-fold higher mortality at 30 days (12.0 vs 2.7% , P = 0. 001). Conclusions This study suggests one possible mechanism underlying worsened outcomes among elderly STEMI patients insofar as advanced chronological age was associated with higher TTMI frame counts and less frequent TIMI Grade 3 flow after rescue/adjunctive PCI. (J Geriatr Gardiol 2005;2(1) :10-14)     

Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25.

AIMS: To determine the effects of age on outcomes in patients with STEMI treated with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). METHODS AND RESULTS: In the ExTRACT-TIMI 25 trial, 20,479 patients with STEMI were randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX was administered to patients >or=75 years, and a reduced dose in those with an estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a subset of patients (n = 73). The exposure to anti-Xa over time was lower in the elderly (AUC(0-12 h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal recurrent myocardial infarction, was greater in patients < 75 years (20%) than > 75 years (6%), but the absolute benefits were similar. When compared with UFH, ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of the excess risk tended to be lower (RR = 1.15) in patients >or= 75 years assigned to ENOX. CONCLUSION: A dose reduction of ENOX in the elderly appears to be helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in both young and elderly patients with STEMI treated with fibrinolysis.     

Angiographic and clinical outcomes associated with direct versus conventional stenting among patients treated with fibrinolytic therapy for ST-elevation acute myocardial infarction

The present study reports outcomes of direct stenting versus conventional stenting, which was performed during adjunctive/rescue percutaneous coronary intervention (n = 556) in the Integrilin and Tenecteplase in Acute Myocardial Infarction trial, the Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis in Myocardial Infarction 23 trial, and the Fibrinolytic and Aggrastat ST-Elevation Resolution trial of fibrinolytic therapy in ST-elevation myocardial infarction. Direct stenting was associated with a lower rate of death, myocardial infarction, or congestive heart failure during hospitalization and at 30 days and was independently associated with improved in-hospital outcomes (odds ratio 0.44, 95% confidence interval 0.23 to 0.85, p = 0.014).     

Outcomes of Patients with Coronary Artery Perforation Complicating Percutaneous Coronary Intervention and Correlations with the Type of Adjunctive Antithrombotic Therapy: Pooled Analysis from REPLACE-2, ACUITY, and HORIZONS-AMI Trials

Background: The lack of a specific counteragent to bivalirudin may complicate the management of patients with coronary artery (CA) perforation during percutaneous coronary intervention (PCI).
Aim: Assess outcomes of patients with CA perforation from three PCI trials comparing intravenous bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition versus unfractionated heparin (UFH) plus GP IIb/IIIa.
Methods: A pooled analysis of patients treated with PCI in three randomized trials including REPLACE-2, ACUITY, and HORIZONS-AMI.
Results: Among a total of 12,921 patients, CA perforation occurred in 35 patients (0.27%). By multivariable analysis, baseline creatinine clearance was the only independent predictor of CA perforation (per 10 mL/min decrease, odds ratio [95% confidence interval]= 1.28 [1.11, 1.47], P = 0.0007). At 30 days, patients with versus without CA perforation had significantly (all P values ≤0.001) higher rates of 30-day mortality (11.4% vs. 1.0%), myocardial infarction (MI) [Q wave: 22.9% vs. 5.7%; non-Q wave: 17.1% vs. 4.9%], target vessel revascularization (TVR) [20.1% vs. 1.8%], and composite end-point of death/MI/TVR (31.4% vs. 7.8%). Patients assigned to bivalirudin versus UFH plus a GP IIb/IIIa inhibitor had nonsignificantly lower rates of death (0% vs. 18.8%, P = 0.08), similar rates of MI (26.7% vs. 25.0%, P = 0.92), significantly lower rates of TVR (6.7% vs. 37.5%, P = 0.04), and similar rates of the composite end-point of death/MI/TVR (35.5% vs. 26.7%, P = 0.54).
Conclusion: In three PCI trials, treatment of patients experiencing CA perforation with adjunctive antithrombotic therapy of bivalirudin monotherapy was not associated with worse outcomes compared to treatment with UFH plus GP IIb/IIIa inhibitors.     

A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention. Results of the Evaluating Enoxaparin Clotting Times (ELECT) Study

OBJECTIVES: The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND: In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS: We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS: The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every approximately 30-s rise. CONCLUSIONS: Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal.