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.     

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.     

Primary angioplasty versus no reperfusion therapy in patients with acute myocardial infarction and a pre-hospital delay of > 12-24 hours: results from the pooled data of the maximal individual therapy in acute myocardial infarction (MITRA) registry and the myocardial infarction registry (MIR)

OBJECTIVE: In patients with acute myocardial infarction (AMI), treatment with thrombolysis is superior to no reperfusion therapy only up to 12 hours after the onset of symptoms. There are no data addressing whether this time limit is also justified for treatment with primary angioplasty. DESIGN: The pooled data of two German ST-segment elevation AMI registries, the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study and the Myocardial Infarction Registry (MIR), were analyzed. PATIENTS: Out of 22,749 patients, eight hundred and forty-eight with a pre-hospital delay of > 12 hours and < or = 24 hours were treated with either primary angioplasty (94/848; 11.1%) or no reperfusion therapy (754/848; 88.9%). RESULTS: Patients treated with primary angioplasty were 10 years younger (59 years versus 69 years; p = 0.001), more often male [72.3% versus 59.9%; odds ratio (OR) = 0.57; 95% confidence interval (CI) = 0.36-0.92] and less likely to be diabetics (17% versus 27.2%; OR = 0.55; 95% CI = 0.31-0.97). Hospital mortality was 8.5% in patients treated with primary angioplasty compared to 17.1% in patients with no reperfusion therapy (OR = 0.45; 95% CI = 0.21-0.95; p = 0.033) and the combined endpoint (death, reinfarction or stroke) occurred significantly less often (11.7% versus 20.3%; OR = 0.52; 95% CI =0.27-1; p = 0.045). However, multiple logistic regression showed only a non-significant trend for lower mortality (OR = 0.54; 95% CI =0.20-1.23) and the combined endpoint (OR = 0.65; 95% CI = 0.29-1.31) in patients treated with primary angioplasty. CONCLUSIONS: These data show the possibility of a benefit of primary angioplasty over conservative treatment in patients with pre-hospital delays of > 12 up to 24 hours, although multiple logistic regression analysis failed to find significant differences between treatments. This might be due to inadequate study power or a selection bias. These findings encourage further investigation of this subject.     

The TETAMI Trial: The Safety and Efficacy of Subcutaneous Enoxaparin versus Intravenous Unfractionated Heparin and of Tirofiban versus Placebo in the Treatment of Acute Myocardial Infarction for Patients Not Thrombolyzed: Methods and Design

Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non–Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.     

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.     

Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention

OBJECTIVES: We sought to determine the prognostic value of mean platelet volume (MPV) for angiographic reperfusion and six-month mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). BACKGROUND: Mean platelet volume is predictive of unfavorable outcome among survivors of STEMI when measured after the index event. No data are available for the value of admission MPV in patients with STEMI treated with primary PCI. METHODS: Blood samples for MPV estimation, obtained on admission in 398 consecutive patients presenting with STEMI, were measured before primary PCI. Follow-up up to six months was performed. RESULTS: No-reflow was significantly more frequent in patients with high MPV (> or =10.3 fl) compared with those with low MPV (<10.3 fl) (21.2% vs. 5.5%, p < 0.0001). The MPV was correlated strongly with corrected Thrombolysis In Myocardial Infarction frame count (CTFC) (r = 0.698, p < 0.0001). Kaplan-Meier survival analysis showed six-month mortality rate of 12.1% in patients with high MPV versus 5.1% in low MPV group (log rank = 6.235, p = 0.0125). After adjusting for baseline characteristics, high MPV remained a strong independent predictor of no-reflow (odds ratio [OR] 4.7, 95% confidence interval [CI] 2.3 to 9.9, p < 0.0001), CTFC > or =40 (OR 10.1, 95% CI 5.7 to 18.1, p < 0.0001), and mortality (OR 3.2, 95% CI 1.1 to 9.3, p = 0.0084). Abciximab administration resulted in significant mortality reduction only in patients with high MPV values (OR 0.02, 95% CI 0.01 to 0.48, p = 0.0165). CONCLUSIONS: Mean platelet volume is a strong, independent predictor of impaired angiographic reperfusion and six-month mortality in STEMI treated with primary PCI. Apart from prognostic value, admission MPV may also carry further practical, therapeutic implications.     

Effect of impaired myocardial reperfusion on left ventricular remodeling in patients with anterior wall acute myocardial infarction treated with primary coronary intervention

We assessed the effect of impaired myocardial blush after primary coronary intervention (PCI) on left ventricular remodeling in patients with ST-segment elevation myocardial infarction (STEMI). The study population consisted of 145 patients with first anterior STEMI that was treated successfully (Thrombolysis In Myocardial Infarction grade 3 flow) with PCI. Left ventricular remodeling was defined as an increase of > or =20% in end-diastolic volume based on repeated echocardiographic measurements in patients. The study population was divided into 2 groups according to the presence (myocardial blush grade [MBG] 2 to 3, n = 86) or absence (MBG 0 to 1, n = 59) of myocardial reperfusion. Left ventricular remodeling appeared in 21% of the entire study group. Poor myocardial blush after PCI was associated with an increased rate of remodeling compared with good myocardial reperfusion (32% vs 14%, hazard ratio 2.308, 95% confidence interval [CI] 1.21 to 4.39, p=0.014). Symptoms of heart failure were observed significantly more often in patients with MBG 0 to 1 (35.6% vs 18.6%, p = 0.032) than in patients with MBG 2 to 3. In multivariate analysis, only age (odds ratio 0.96, 95% CI 0.92 to 0.99, p = 0.02) and MBG 0 to 1 (odds ratio 3.15, 95% CI 1.35 to 7.31, p = 0.008) were associated with left ventricular dilation. In conclusion, impaired microvascular reperfusion is associated with left ventricular remodeling and development of congestive heart failure in patients with anterior STEMI that is treated with primary coronary angioplasty.     

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.     

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.     

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.     

Efficacy and Safety of Low-Molecular-Weight Heparins As An Adjunct to Thrombolysis in Acute ST-Elevation Myocardial Infarction

A 48-hour course of intravenous unfractionated heparin (UFH) is the standard of treatment in conjunction with fibrin-specific thrombolysis in ST-elevation myocardial infarction (STEMI). In recent trials, the efficacy and safety of in-hospital administration of subcutaneous low-molecular-weight heparins (LMWH), previously proven effective in non-ST-elevation acute coronary syndromes, have been investigated in the setting of STEMI. The aim of this review was to evaluate the available evidence supporting the use of LMWH in STEMI.Overall, about 27,000 patients treated with various thrombolytic regimens, were included in 12 open-label randomized clinical trials, where dalteparin, reviparin or enoxaparin were administered. While acknowledging the wide variability in study dimensions, designs and end-points, a higher efficacy of LMWH was observed overall as compared to placebo, and also to UFH (mainly as regards the occurrence of reinfarction). As regards safety, bleedings were more frequent than placebo and comparable to UFH in LMWH groups, with the exception of the pre-hospital ASSENT-3 PLUS trial, where in elderly patients, enoxaparin had an incidence of intracranial hemorrhage twice higher than UFH. In a recent double-blind, randomized, mega-trial including over 20,000 patients, the superior efficacy on in-hospital and 30-day adverse cardiac events (namely reinfarction), and comparable safety on intracranial bleedings, of enoxaparin compared to UFH, was shown.In conclusion, in-hospital subcutaneous administration of dalteparin, reviparin and enoxaparin, as an adjunct to various thrombolytics in STEMI, appears feasible and at least as effective and safe as 48-hour intravenous treatment with UFH. In accordance with the available strongest evidence, an initial intravenous bolus of enoxaparin followed by twice daily subcutaneous administration for about 1 week should be the preferred regimen, and should be strongly considered instead of intravenous UFH. Along with its easiness of use, not requiring laboratory monitoring, subcutaneous administration of LMWH following STEMI treated with thrombolysis allows extended antithrombotic treatment, while permitting early mobilization (and rehabilitation) of patients.Key Words: ST-elevation acute myocardial infarction, enoxaparin, dalteparin, reviparin, unfractionated heparin.     

Prior aspirin users with acute non-ST-elevation coronary syndromes are at increased risk of cardiac events and benefit from enoxaparin

BACKGROUND: The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. METHODS: The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. RESULTS: The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). CONCLUSION: Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated.     

Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial.

AIMS: In high risk patients with non-ST elevation acute coronary syndromes (ACS), enoxaparin is generally preferred to unfractionated heparin (UFH). However, less is known about the relative merits of these two forms of heparin in patients receiving concomitant glycoprotein IIb/IIIa inhibitors. METHODS AND RESULTS: The A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987 patients with non-ST elevation ACS were randomised to receive either enoxaparin or UFH in combination with aspirin and tirofiban. Inclusion required either ST depression or cardiac biomarker elevation. While the selection of an early management strategy (invasive or conservative) was at the discretion of the local investigator, investigators were asked to designate their plans for an invasive or conservative strategy on the case record form. An early conservative strategy was specified for 1778 patients (45%); this subgroup forms the population for the present analyses. Among patients with a planned conservative strategy, baseline characteristics were similar between those randomised to UFH (n = 872) and those randomised to enoxaparin (n = 906). The primary endpoint of death, new MI, or documented refractory ischaemia within 7 days of randomisation occurred in 10.6% of patients randomised to UFH and 7.7% of patients randomised to enoxaparin (HR 0.72; 95% CI 0.53-0.99; p = 0.04). The combined rate of TIMI major, minor, or loss no-site bleeding was 1.3% in patients treated with UFH and 1.8% in those treated with enoxaparin (p = ns). CONCLUSIONS: When a conservative approach to catheterisation and PCI was planned for ACS patients receiving tirofiban and aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs UFH.     

Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention

OBJECTIVES: The purpose of this study was to determine the clinical and angiographic correlates and outcomes of patients with suboptimal coronary flow after primary percutaneous coronary interventions (PCI). BACKGROUND: The clinical and angiographic correlates and outcomes of Thrombolysis in Myocardial Infarction (TIMI) < or =2 flow in patients treated with primary PCI are not known. METHODS: We evaluated 3,362 patients with ST elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction trials, who underwent primary PCI. RESULTS: Post-procedural final TIMI < or =2 flow occurred in 232 (6.9%) patients. Multivariate analysis identified age > or =70 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), diabetes (OR 1.9; 95% CI, 1.3 to 2.7), symptom onset to emergency room presentation (OR 1.1; 95% CI, 1.1 to 1.2); initial TIMI < or =1 flow (OR 3.2; 95% CI, 1.9 to 5.5), and left ventricular ejection fraction <50% (OR 1.7; 95% CI, 1.2 to 2.4) as independent correlates of final TIMI < or =2 flow. In-hospital (composite of reinfarction, ischemic target vessel revascularization, or death, as well as these events individually) and one-year (reinfarction and/or death) events occurred more frequently in patients with TIMI < or =2 flow. The Cox proportional hazards model identified TIMI < or =2 flow to be independently associated with one-year mortality (hazard ratio 3.8, 95% CI, 2.5 to 5.7). CONCLUSIONS: Final TIMI < or =2 flow, although uncommon after primary PCI, was strongly associated with hospital and one-year adverse events. The clustering of final TIMI < or =2 flow in high-risk groups may partially explain the poor prognosis of these patients. Awareness of these risk factors may be useful to clinicians to triage and treat patients undergoing primary PCI.     

Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction

ObjectivesThis study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y₁₂ inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).BackgroundEarly dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y₁₂ inhibitor effect is delayed and varies according to formulation administered.MethodsThe COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion.ResultsA total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y₁₂ reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40).ConclusionsOral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.     

Impact of abciximab on mortality and reinfarction in patients with acute ST‐segment elevation myocardial infarction treated with primary stenting

Objectives: To combine data from all randomized trials of abciximab versus placebo or open‐label control in patients with STEMI treated with primary stenting to assess the short‐term and long‐term mortality, reinfarction, and bleeding complications. Background: Clinical trials of adjunctive abciximab therapy in patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary stenting have produced conflicting results. Methods: Formal searches of electronic databases (Medline, Cochrane) from January 1990 to April 2009 were performed. Five trials randomizing 2,937 patients (1,475 in the abciximab group, 1,462 in the placebo group) were included in the analysis. Results: When compared with placebo, abciximab was not associated with a significant reduction in the odds of 30‐day (OR 0.71, 95% CI: 0.45–1.14, P = 0.16) or long‐term (OR 0.85, 95% CI: 0.48–1.50, P = 0.57) mortality. Similarly, the rate of reinfarction was not statistically different at 30 days (OR 0.59, 95% CI: 0.30–1.17, P = 0.13) or at long‐term follow‐up (OR 0.67; 95% CI: 0.39–1.16, P = 0.16). However, when trials with upstream use of thienopyridines were excluded, abciximab was associated with a significant reduction in the composite of death or reinfarction at 30 days (OR 0.45; 95% CI: 0.26–0.77, P = 0.004) but not at long‐term follow‐up (OR 0.59; 95% CI: 0.27–1.28, P = 0.18). Conclusion: Routine use of abciximab in patients with STEMI treated with primary stenting may reduce short‐term rates of death or reinfarction in patients not administered preprocedural thienopyridine therapy, but does not appear to be beneficial in those who receive preprocedural thienopyridines. © 2009 Wiley‐Liss, Inc.     

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study

ObjectivesThe aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention.BackgroundPrasugrel is one of the preferred P2Y₁₂ platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients.MethodsBetween September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days.ResultsOf 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36).ConclusionsThis observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).     

The incidence, predictors, and outcomes of early reinfarction after primary angioplasty for acute myocardial infarction

OBJECTIVES: We sought to identify the incidence, predictors, and clinical consequences of one-month reinfarction (RE-MI) in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: One-month reinfarction after AMI significantly increases long-term mortality; however, little is known about the incidence and predictors of RE-MI in patients undergoing primary angioplasty. METHODS: We analyzed data from 3,646 patients who underwent primary PCI in the Primary Angioplasty in Acute Myocardial Infarction (PAMI) studies. We studied the incidence, correlates, and clinical outcomes of 30-day RE-MI. RESULTS: Reinfarction within one month of index hospitalization occurred in 77 (2.1%) of patients. In multivariate analysis, admission Killip class >1 (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.09 to 3.76), left ventricular ejection fraction <50% (OR 2.49, 95% CI 1.30 to 4.74), final coronary stenosis >30% (OR 2.57, 95% CI 1.28 to 5.15), and presence of coronary dissection (OR 2.40, 95% CI 1.36 to 4.24) and thrombus (OR 2.36, 95% CI 1.23 to 4.53) on the final angiogram were independent correlates of RE-MI. One-month reinfarction was independently associated with death (OR 7.14, 95% CI 3.28 to 15.5) and ischemic target vessel revascularization (I-TVR) (OR 15.0, 95% CI 8.68 to 26.0) at six months. CONCLUSIONS: We conclude that, although early RE-MI is uncommon in patients treated by primary PCI, it is a significant independent predictor of death and I-TVR at six months. Admission Killip class >1 and left ventricular systolic dysfunction were associated with higher incidence of RE-MI. Our results suggest that optimal revascularization during primary PCI may decrease RE-MI rates.     

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.     

Effectiveness of primary percutaneous coronary intervention compared with that of thrombolytic therapy in elderly patients with acute myocardial infarction

Background

Few data exist from a community-based perspective on the relative effectiveness of primary percutaneous coronary intervention (PCI) as compared with thrombolytic therapy (TT) in elderly patients with ST-elevation myocardial infarction (STEMI), particularly in the current era of coronary stents and newer antithrombotic agents.

Methods

We evaluated data from patients, aged ≥70 years, with STEMI who were enrolled in the Global Registry of Acute Coronary Events study between April 1999, and September 2002.

Results

Of the 2975 elderly patients eligible for reperfusion therapy, 365 (12.7%) underwent primary PCI and 769 (26.7%) received TT. The median delay from hospital arrival to therapy was 105 minutes for primary PCI and 40 minutes for TT. Inhospital complications for primary PCI versus TT included mortality (13.5% vs 14.8%), reinfarction (1.1% vs 5.7%), composite of death or reinfarction (14.3% vs 18.7%), cardiogenic shock (11.3% vs 11.6%), major bleeding (8.6% vs 5.9%), and stroke (1.1% vs 2.8%). After adjustment for baseline differences and propensity score, patients receiving primary PCI showed a lower rate of reinfarction (odds ratio [OR], 0.15; 95% CI, 0.05-0.44) and mortality (OR, 0.62; 95% CI, 0.39-0.96) and the composite of reinfarction or death (OR, 0.53; 95% CI, 0.35-0.79), with no difference in other outcome measures.

Conclusion

Our data suggest that, compared with TT, primary PCI is associated with a decrease in reinfarction and mortality, with no change in other outcome measures, in elderly patients with STEMI. These findings from an observational registry require further confirmation in future randomized clinical trial assessing the optimal reperfusion strategy in the elderly cohort with STEMI.