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 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.     

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.     

Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.

OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and subsequently undergo percutaneous coronary intervention (PCI) by analyzing data from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial. BACKGROUND: Limited data are available on the use of ENOX compared with UFH as adjunctive therapy in STEMI patients treated with fibrinolytic therapy and subsequent PCI. METHODS: A total of 20,479 STEMI patients who received fibrinolytic therapy were randomized to a strategy of ENOX throughout index hospitalization or UFH for at least 48 h, with blinded study drug to continue if PCI was performed. The primary end point of death or recurrent MI through 30 days was compared for ENOX versus UFH among the patients who underwent subsequent PCI (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027). Among patients who underwent PCI by 30 days, the primary end point occurred in 10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p = NS). Results were similar when PCI was carried out in patients receiving blinded study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration was associated with a reduced risk of death or recurrent MI without difference in the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy followed by PCI is superior to UFH and provides a seamless transition from the medical management to the interventional management phase of STEMI without the need for introducing a second anticoagulant in the cardiac catheterization laboratory.     

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention

Objectives : The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI). Background : Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. Methods : Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié‐Salpêtrière registry of ischemic coronary syndromes (e‐PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity‐weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. Results : Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti‐Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12–0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16–0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12–0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17–0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). Conclusions : In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley‐Liss, Inc.     

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.     

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.     

Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation acute myocardial infarction: a substudy of the randomized double blind CLARITY-TIMI 28 trial

Background Fibrinolytic therapy for acute ST-elevation myocardial infarction (STEMI) is frequently limited by delays in administration and by incomplete reperfusion or reocclusion of the infarct-related artery. Intensified prehospital management of STEMI may shorten time to treatment and improve outcomes. Methods We carried out a prospective substudy in 11 ambulance systems in 216 of the 3,491 patients with STEMI who were enrolled in the CLARITY-TIMI 28 trial. They were randomized in the ambulance to clopidogrel (n = 109) or placebo (n = 107) along with fibrinolysis, aspirin, and heparin. The primary endpoint was the composite of an occluded infarct-related artery (TIMI flow grade 0 or 1), or death or recurrent myocardial infarction before angiography. Results All patients received a fibrin-specific lytic and the baseline characteristics in both groups were comparable. The incidence of the primary endpoint was 16.5% in the clopidogrel-treated and 27.1% in the placebo patients (adj OR 0.62, 95% CI 0.31–1.21, p = 0.16), an effect that was consistent with the effects seen in the in-hospital patients in the main CLARITY-TIMI 28 trial. Prehospital clopidogrel therapy reduced the incidence of an occluded infarct-related artery on the predischarge angiogram (11.8% vs. 22.3%, adj OR 0.52, 95% CI 0.24–1.13, p = 0.10). The 30-day incidence of cardiovascular death, recurrent MI or recurrent myocardial ischemia requiring urgent revascularization was 12.8% vs. 14.0% (adj OR 1.07, 95% CI 0.48–2.39, p = 0.87). Early TIMI major bleeding occurred in no clopidogrel patients compared with two placebo patients (1.9%). Conclusions Addition of clopidogrel to medical reperfusion of STEMI with fibrinolysis, heparin, and aspirin before reaching the hospital is feasible in medically equipped ambulances without an apparent increase in bleeding. Furthermore, prehospital clopidogrel tended to show better early coronary patency compared to placebo, a result consistent with that observed in patients randomized in-hospital in the CLARITY-TIMI 28 trial.     

Impact of delay in door-to-needle time on mortality in patients with ST-segment elevation myocardial infarction

Fibrinolytic therapy is the most common reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI), particularly in smaller centers. Previous studies evaluated the relation between time to treatment and outcomes when few patients were treated within 30 minutes of hospital arrival and many did not receive modern adjunctive medications. To quantify the impact of a delay in door-to-needle time on mortality in a recent and representative cohort of patients with STEMI, a cohort of 62,470 patients with STEMI treated using fibrinolytic therapy at 973 hospitals that participated in the National Registry of Myocardial Infarction from 1999 to 2002 was analyzed. Hierarchical models were used to evaluate the independent effect of door-to-needle time on in-hospital mortality. In-hospital mortality was lower with shorter door-to-needle times (2.9% for < or =30 minutes, 4.1% for 31 to 45 minutes, and 6.2% for >45 minutes; p <0.001 for trend). Compared with those experiencing door-to-needle times < or =30 minutes, adjusted odd ratios (ORs) of dying were 1.17 (95% confidence interval [CI] 1.04 to 1.31) and 1.37 (95% CI 1.23 to 1.52; p for trend <0.001) for patients with door-to-needle times of 31 to 45 and >45 minutes, respectively. This relation was particularly pronounced in those presenting within 1 hour of symptom onset to presentation time (OR 1.25, 95% CI 1.01 to 1.54; OR 1.54, 95% CI 1.27 to 1.87, respectively; p for trend <0.001). In conclusion, timely administration of fibrinolytic therapy continues to significantly impact on mortality in the modern era, particularly in patients presenting early after symptom onset.     

ExTRACT-TIMI 25 in perspective: key lessons regarding enoxaparin as an adjunct to fibrinolytic therapy

Unfractionated heparin (UFH) for 48 h has been the traditional standard anticoagulant with fibrinolytics. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction (ExTRACT)-Thrombolysis in Myocardial Infarction (TIMI) 25 trial prospectively studied the usefulness of enoxaparin and found that in patients treated with fibrinolysis, enoxaparin administered throughout the index hospitalization was superior to the standard 48-h UFH infusion. However, enoxaparin increased major bleeding. The data from this large trial were further analyzed across various subgroups and these results support the use of enoxaparin in a broad range of patients. The ExTRACT-TIMI 25 trial employed a novel dosing regimen for enoxaparin adjusted for age and renal function, which was designed to minimize bleeding risk while maintaining the beneficial effects of enoxaparin. Based on the evidence from this trial, the 2007 ST-segment elevation myocardial infarction guidelines now preferentially recommend enoxaparin to be administered throughout the index hospitalization as per the dosing regimen used in ExTRACT-TIMI 25 in most patients treated with fibrinolytic therapy.     

Comparison of bleeding and in-hospital mortality in Asian-Americans versus Caucasian-Americans with ST-elevation myocardial infarction receiving reperfusion therapy

Concern has been raised that Asian-Americans may have a higher bleeding risk than Caucasian-Americans when treated with fibrinolytic and antithrombotic agents. To date there is limited evidence to support or refute this hypothesis or evaluate bleeding risk and its related outcomes in Caucasian-Americans versus Asian-Americans with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI). We evaluated Asian-Americans and Caucasian-Americans with STEMI receiving reperfusion therapy in the National Registry of Myocardial Infarction (NRMI) 4 and 5 (n = 90,317). We studied risk-adjusted major bleeding and in-hospital mortality. Major bleeding rates after fibrinolysis were similar in Asian-Americans (n = 705) and Caucasian-Americans (n = 42,243, 11.1% vs 10.3%, adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.69 to 1.36, p = 0.5002). Although the observed major bleeding rate was higher in Asian-Americans (n = 1,037) compared to Caucasian-Americans (n = 46,332) treated with PPCI (10.3% vs 7.8%, p = 0.0036), these rates differed only marginally after adjusting for baseline clinical variables (OR 1.24, 95% CI 0.97 to 1.59). Overall adjusted mortality was similar in Asian-Americans and Caucasian-Americans when treated with fibrinolysis (OR 0.96, 95% CI 0.56 to 1.65) or with PPCI (OR 1.35, 95% CI 0.85 to 2.13). Major bleeding after PPCI or fibrinolysis was associated with similar increased risks for mortality in these ethic groups. In conclusion, despite suggestions to the contrary, Asian-Americans with STEMI treated with fibrinolysis or PPCI had similar bleeding and bleeding-related mortality risks compared to Caucasian-Americans. Given the genotypic and phenotypic differences between the 2 cohorts, similar studies in the rapidly growing Asian-American population are needed to confirm our findings and to understand the safety and effectiveness of newer potent antiplatelet and antithrombotic agents in patients with coronary syndromes.     

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 angiographic and other findings and mortality in non-ST-segment elevation versus ST-segment elevation myocardial infarction in patients undergoing early invasive intervention

We sought to compare the angiographic findings and mortality in patients with non-ST-segment elevation (NSTEMI) versus ST-segment elevation myocardial infarction (STEMI) undergoing early invasive intervention. Of 11,872 patients enrolled in the Korean Acute Myocardial Infarction Registry from November 2005 to January 2008, we studied patients with NSTEMI undergoing early invasive intervention (n = 1,486) and those with STEMI undergoing primary percutaneous coronary intervention (n = 4,392). Multivessel coronary disease, baseline Thrombolysis In Myocardial Infarction (TIMI) flow grade 3, and the left circumflex artery as a culprit lesion occurred more frequently in patients with NSTEMI than in those with STEMI. Those with NSTEMI had a significantly lower mortality rate than those with STEMI during a median follow-up of about 12 months (3.8% vs 6.7%, p <0.001). In the patients with NSTEMI, the independent predictors of mortality included postprocedural TIMI flow grade 0 to 2 (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.01 to 9.29, p = 0.047) and multivessel coronary disease (HR 3.83, 95% CI 1.36 to 10.81, p = 0.010) but not baseline TIMI flow or infarct location. However, baseline TIMI flow grade 0 to 2 (HR 1.56, 95% CI 1.03 to 2.36, p = 0.035), anterior infarction (HR 1.69, 95% CI 1.28 to 2.23, p <0.001), multivessel coronary disease (HR 1.45, 95% CI 1.10 to 1.91, p = 0.008), and postprocedural TIMI flow grade 0 to 2 (HR 2.00, 95% CI 1.42 to 2.82, p <0.001) were all independent predictors of mortality in the patients with STEMI. In conclusion, the angiographic findings in patients from NSTEMI differ from those in patients with STEMI. Postprocedural TIMI flow and multivessel coronary disease were independent predictors of mortality in patients with NSTEMI undergoing early invasive intervention.     

Contemporary clinical outcomes of primary percutaneous coronary intervention in elderly versus younger patients presenting with acute ST-segment elevation myocardial infarction

Background: Primary percutaneous coronary intervention (PPCI) is the choice reperfusion strategy for acute ST‐segment elevation myocardial infarction (STEMI). However, data on PPCI in elderly patients are sparse. This study determined clinical outcome post‐PPCI in elderly versus younger patients with STEMI. Methods and Results: A cohort of 790 consecutive STEMI patients was studied for survival and major adverse cardiovascular events (MACE) after PPCI using a precise cardiac catheterization protocol. Patients were divided into two groups: those ≥75 years (elderly) and those <75 years. Median door‐to‐balloon time (DBT) was 82 minutes in the elderly versus 66 minutes in the younger group (P = 0.002). In‐hospital all‐cause mortality was higher in the elderly group (15.5% vs. 2.7%, P < 0.001). In elderly patients, MACE were found to be higher (32.3% vs. 16.1%, P < 0.001). Using a multivariate logistic regression analysis, age (odds ratio [OR]= 1.04, 95% confidence interval [CI]= 1.02–1.05, P < 0.001), diabetes (OR = 2.17, 95% CI = 1.33–3.53, P = 0.002), renal failure (OR = 3.75, 95% CI = 1.30–10.79, P = 0.014) and coronary artery disease (OR = 1.61, 95% CI = 1.00–2.59, P = 0.050) were associated with higher in‐hospital MACE, while age (OR = 1.05, 95% CI = 1.02–1.08, P = 0.001), diabetes (OR = 2.18, 95% CI = 1.06–4.47, P = 0.034) and renal failure (OR = 6.65, 95% CI = 2.01–22.09, P = 0.002) were associated with higher in‐hospital mortality. Kaplan–Meier 1‐year survival rate was lower in the elderly. Conclusions: In a contemporary population of STEMI patients treated with PPCI, overall in‐hospital MACE and mortality remain higher in elderly compared to younger patients. Although partly due to higher burden of preexisting comorbidities, a higher DBT may also be responsible. (J Interven Cardiol 2011;24:357–365)     

Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality

OBJECTIVES: We hypothesized that impaired renal function would also be associated with poorer clinical outcomes among patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolysis. BACKGROUND: Previous studies have demonstrated that impaired renal function is associated with poorer clinical outcomes in the setting of unstable angina and non-STEMI and after percutaneous coronary intervention. METHODS: Data were drawn from the Thrombolysis In Myocardial Infarction (TIMI)-10, TIMI-14, and Intravenous nPA for the Treatment of Infarcting Myocardium Early (InTIME-II) trials. RESULTS: Within each TIMI risk score (TRS) for STEMI category (0 to 2, 3 to 4, >/=5), 30-day mortality increased stepwise among patients with normal (creatinine [Cr] 1.2 to 2 mg/dl), and severely (Cr >2.0 mg/dl) impaired renal function (p < 0.001) and in patients with normal (creatinine clearance [CrCl] >/=90 ml/min), mildly (60 to <90 ml/min), moderately (30 to <60 ml/min), and severely (<30 ml/min) impaired CrCl (p < 0.001). Impaired renal function was associated with increased mortality after adjusting for previously identified correlates of mortality (using Cr: odds ratio [OR] for mild impairment 1.52, 95% confidence interval [CI] 1.30 to 1.77, p < 0.001; OR for severe impairment 3.73, 95% CI 2.55 to 5.45, p < 0.001; using CrCl: OR for mild impairment 1.38, 95% CI 1.10 to 1.73, p = 0.006; OR for moderate impairment 2.06, 95% CI 1.59 to 2.66, p < 0.001; OR for severe impairment 3.81, 95% CI 2.57 to 5.65, p < 0.001). CONCLUSIONS: In the setting of STEMI, elevated Cr and/or impaired CrCl on presentation is associated with increased mortality, independent of other conventional risk factors and TRS. This association does not appear to be mediated by reduced fibrinolytic efficacy among patients with impaired renal function or by the presence of congestive heart failure on presentation.     

Effectiveness of primary percutaneous coronary intervention for acute ST-elevation myocardial infarction from a 5-year single-center experience

Primary percutaneous coronary intervention (PCI) is currently viewed as the preferred reperfusion strategy in patients with ST-elevation acute myocardial infarction (STEMI). This method was introduced in our hospital in 2000. From January 1, 2000, to December 31, 2004, a total of 2,393 consecutive patients with STEMI were admitted (27% transferred from 9 non-PCI hospitals and 31 prehospital emergency units/outpatient clinics). Of these patients, 1,666 (70%) underwent urgent coronary angiography and primary PCI. Platelet glycoprotein llb/llla inhibitors were used in 40% and stent placement, in 78%. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow was documented in 86%. Intra-aortic balloon counterpulsation was used in 6%; mechanical ventilation, in 8.6%; and inotropic drugs/vasopressors, in 15.8%. Mortality rates in patients with Killip's class I or II ranged from 1% to 4.9% without negative influence of ischemic time. In patients with Killip's class III or IV, mortality rates increased from 18% to 54% with increasing ischemic delay up to 6 hours (p = 0.06) and remained at around 40% afterward. Independent predictors of mortality were age (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p = 0.04), resuscitated cardiac arrest (OR 2.44, 95% CI 1.18 to 5.05, p = 0.02), and postprocedural TIMI flow (OR 0.31, 95% CI 0.16 to 0.59). Overall mortality rates of patients who underwent a primary PCI strategy from 2000 to 2004 were significantly lower than in the control group of 152 consecutive patients who underwent thrombolysis from 1995 to 1996 (6.2% vs 16.4%; p <0.001). In conclusion, introduction of a primary PCI strategy significantly decreased hospital mortality in our unselected group of patients with STEMI compared with the thrombolytic era. Our study further emphasized the importance of shortening myocardial ischemic time, particularly in the presence of severe heart failure on admission.     

N-terminal pro-B-type natriuretic peptide is associated with adverse short-term clinical outcomes in patients with acute ST-elevation myocardial infarction underwent primary percutaneous coronary intervention

BACKGROUND: Increased level of N-terminal pro-B type natriuretic peptide (NT-proBNP) is known to be associated with adverse outcome in patients with acute coronary syndrome. We evaluated early outcomes of patients with acute ST-elevated myocardial infarction (STEMI) according to the level of NT-proBNP as a substudy of Korean Acute Myocardial Infarction Registry (KAMIR). METHODS: Study population consisted of 1052 consecutive patients (mean 61.3+/-12.8 years old, male 73.2%) with STEMI of onset <12 h who underwent primary percutaneous coronary intervention (PCI) and who had baseline NT-proBNP level by electrochemiluminescence immnunoassay (ECLIA, NT-proBNP kit, Roche Diagnostics, Mannheim, Germany). The study subjects were divided into two groups according to the level of serum NT-proBNP. RESULTS: Patients with NT-proBNP level >991 pg/mL (n=329, 57.1% male) had lower left ventricle ejection fraction (LVEF) (47.8+/-11.8% vs. 53.0+/-10.8%, p<0.001), needed longer intensive care (3.7+/-3.6 days vs. 2.8+/-2.4 days, p<0.001) and had higher in-hospital mortality (1.3% vs. 7.4%, p<0.001) than those with NT-proBNP level991 pg/mL) (OR 3.70, 95% CI 1.14 to 12.03, p=0.030), old age (>or=70 years) (OR 4.71, 95% CI 1.43 to 15.52, p=0.011), advanced Killip class (>1) (OR 4.96, 95% CI 1.58 to 15.53, p=0.006), male gender (OR 5.67, 95% CI 1.45 to 22.21, p=0.013) and TIMI flow 0 before PCI (OR 5.04, 95% CI 1.08 to 23.41, p=0.039). CONCLUSIONS: This study suggests that baseline NT-proBNP level is associated with short term mortality in patients with STEMI underwent primary PCI.     

Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome: An ENTIRE-TIMI 23 substudy.

AIMS: Prior studies suggest that acute coronary syndromes (ACSs) are associated with endothelial activation and that this is of prognostic significance. We hypothesized that endothelial activation, as measured by a rise in von Willebrand Factor (DeltavWF), was influenced by the thrombolysis in myocardial infarction flow grade (TFG), the corrected TIMI frame count (CTFC) and the choice of anticoagulant therapy after fibrinolysis in ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: Data were drawn from the enoxaparin and tenecteplase tissue plasminogen activator (TNK-tpa) with or without GPIIb/IIIa inhibitor as the reperfusion strategy in the STEMI trial (ENTIRE-TIMI 23). Three hundred and fourteen patients had serial measurements of vWF (baseline and 48-72 h) and angiographic data available. TFG<3 (P=0.0042) or CTFC>/=40 at 60 min (P=0.0035) were associated with a higher DeltavWF. DeltavWF >/=75th percentile was associated with a higher incidence of death or myocardial infarction (MI) at 30 days, compared with <75th percentile (11.2 vs. 4.1%, P=0.027). Enoxaparin independently reduced the DeltavWF (P=0.019) and also the composite of death or MI (OR 0.33, 95% CI 0.12-0.91, P=0.03) compared with unfractionated heparin. CONCLUSION: In STEMI treated by fibrinolysis, coronary flow at 60 min and choice of adjunctive anticoagulant appear to be independent determinants of DeltavWF. Enoxaparin is independently associated with a reduction in DeltavWF and a reduction in death or MI. The clinical benefits of enoxaparin as an adjunctive treatment in STEMI may be mediated in part by a reduction in vWF release.     

Prognostic impact of acute beta-blocker therapy on top of aspirin and angiotensin-converting enzyme inhibitor therapy in consecutive patients with ST-elevation acute myocardial infarction

The prognostic effect of beta-blocker treatment on ST-elevation acute myocardial infarction (STEMI) is controversially discussed in the era of reperfusion therapy. From the German multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS (MITRA PLUS), 17,809 consecutive patients with STEMI treated with a guideline-recommended therapy with aspirin and an angiotensin-converting enzyme inhibitor were investigated; the prognostic effect of additional acute beta-blocker treatment was analyzed. Patients with cardiogenic shock were excluded. Of included patients, 77.6% received additional acute beta-blocker treatment and 22.4% did not. Patients with beta-blocker treatment were younger and more often received reperfusion therapy. Acute beta-blocker treatment was associated with a lower hospital mortality (univariate analysis 4.9% vs 10.8%, p <0.001; multivariate analysis odds ratio [OR] 0.70, 95% confidence interval [CI] 0.61 to 0.81). Acute beta blockade was significantly associated with a lower hospital mortality in patients without (OR 0.66, 95% CI 0.56 to 0.79) and with (OR 0.76, 95% CI 0.60 to 0.98) reperfusion therapy. The greatest benefit of acute beta-blocker treatment, measured by the number needed to treat to save 1 life, was found in patients with anterior MI, a heart rate > or =80 beats/min, no reperfusion therapy, female gender, and age > or =65 years. In conclusion, acute beta-blocker therapy in the clinical practice of treating patients with STEMI, in addition to aspirin and angiotensin-converting enzyme inhibitor therapy, was independently associated with a significant decrease in hospital mortality in patients with and without reperfusion therapy. High-risk patients with STEMI, such as elderly patients and patients without reperfusion therapy, showed a greater benefit of acute beta-blocker therapy than low-risk patients with STEMI.     

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.