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.     

Use of anticoagulants in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention: a potential role for enoxaparin

Unfractionated heparin (UFH) is currently given as the standard anticoagulant therapy in ST-elevation myocardial infarction (STEMI) patients, including those undergoing percutaneous coronary intervention (PCI). Recent data, however, have shown lower rates of death or recurrent myocardial infarction (MI) with the low-molecular-weight heparin (LMWH) enoxaparin compared with UFH in STEMI patients treated with thrombolytics, off-setting an increase in major bleeding. This review compares the use of enoxaparin with UFH in STEMI patients undergoing PCI, within the context of available evidence for other anticoagulant drugs. Evidence is accumulating for the preferential use of enoxaparin in STEMI patients undergoing PCI.     

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.     

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.     

Enoxaparin 0.3 mg/kg IV supplement for patients transitioning to PCI after subcutaneous enoxaparin therapy for NSTE ACS: A subgroup analysis from the SYNERGY trial

Objective : To explore clinical and bleeding outcomes in patients enrolled in the SYNERGY trial who had percutaneous coronary intervention (PCI) based on adherence to the dosing regimens of enoxaparin mandated by the protocol. Background : In SYNERGY, 4,687 patients underwent PCI during index hospitalization. Patients in the subcutaneous (sc) enoxaparin group were to be given an 0.3 mg/kg IV bolus immediately before PCI if balloon inflation occurred ≥8 hr after their last sc dose of enoxaparin. Methods : The incidence of the 1° efficacy end point (death/myocardial infarction [MI] post PCI and through 30 days), and the rates of post‐PCI in‐hospital TIMI major and GUSTO severe bleeding were compared between patients randomized to unfractionated heparin (UFH) and those randomized to sc enoxaparin who did or did not receive a supplemental IV bolus of enoxaparin in accord with protocol‐mandates. Results : A total of 4,687 patients had PCI; 2,323 were assigned sc enoxaparin and 1,332 received protocol‐mandated IV enoxaparin bolus, while 215 enoxaparin patients received inappropriate IV therapy (either receiving IV enoxaparin before the 8‐hr protocol time or not receiving the IV enoxaparin as directed after 8 hr). Death or MI occurring post PCI through 30‐day follow‐up tended to be lower in the enoxaparin patients who were treated according to protocol than in those who were not (12.3% vs. 14.4%; adjusted P = 0.25), as was TIMI major bleeding (3.0% vs. 4.7%, adjusted P = 0.08). Conclusion : These exploratory analyses show that patients in SYNERGY who received the protocol‐mandated supplemental IV bolus of 0.3 mg/kg enoxaparin before PCI performed 8–12 hr after their last sc enoxaparin dose tended to have improved outcomes compared with those who did not. Strategies to ensure adherence to dosing guidelines of enoxaparin during PCI should be considered. © 2009 Wiley‐Liss, Inc.     

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.     

Comparison of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing an invasive strategy: A meta-analysis of randomized clinical trials

Objective

This meta-analysis was performed to assess the efficacy and safety of bivalirudin compared with unfractionated heparin or enoxaparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI).

Background

Pharmacotherapy for patients undergoing PCI includes bivalirudin, heparin, and GP IIb/IIIa inhibitors. We sought to compare ischemic and bleeding outcomes with bivalirudin versus heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.

Methods

A literature search was conducted to identify fully published randomized trials that compared bivalirudin with heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.

Results

A total of 19,772 patients in 5 clinical trials were included in the analysis (9785 patients received bivalirudin and 9987 patients received heparin plus GP IIb/IIIa inhibitors during PCI). Anticoagulation with bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in no difference in major adverse cardiovascular events (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96 to 1.19), death (OR 0.93, 95% CI 0.72 to 1.21), or urgent revascularization (OR 1.06, 95% CI 0.86 to 1.30). There is a trend towards a higher risk of myocardial infarction (OR 1.12, 95% CI 0.99 to 1.28) but a significantly lower risk of TIMI major bleeding with bivalirudin (OR 0.55, 95% CI 0.44 to 0.69).

Conclusion

In patients who undergo PCI, anticoagulation with bivalirudin as compared with unfractionated heparin or enoxaparin plus GP IIb/IIIa inhibitors results in similar ischemic adverse events but a reduction in major bleeding.     

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.     

Primary percutaneous coronary intervention for ST-elevation myocardial infarction using an intravenous and subcutaneous enoxaparin low molecular weight heparin regimen

Background Enoxaparin use in PCI has been investigated, however its role in primary PCI is less known. Objective To evaluate the role of combination IV + SC enoxaparin in primary PCI in STEMI. Methods 83 consecutive patients with STEMI who underwent primary PCI between January 1, 2005 and January 15, 2008 were included. Anticoagulation was based on our institution’s STEMI protocol; either IV + SC enoxaparin, or IV unfractionated heparin (UFH). Clinical endpoints included MACE, bleeding and net adverse cardiac events (NACE). Results 45 patients received UFH and 37 received IV + SC enoxaparin. There was no difference in the rate of mortality, MACE, or NACE. There was a trend toward more TIMI major and GUSTO moderate and severe bleeding in the UFH group. Conclusions Application of IV + SC enoxaparin strategy for primary PCI in STEMI appears both safe and efficacious. A prospective randomized trial will be necessary to evaluate the safety and efficacy more thoroughly.     

Renal Protection Using Remote Ischemic Peri‐Conditioning During Inter‐Facility Helicopter Transport of Patients With ST‐Segment Elevation Myocardial Infarction: A Retrospective Study

Objective

To assess the impact of remote ischemic peri‐conditioning (RIPC) during inter‐facility air medical transport of ST‐segment elevation myocardial infarction (STEMI) patients on the incidence of acute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI).

Background

STEMI patients who receive pPCI have an increased risk of AKI for which there is no well‐defined prophylactic therapy in the setting of emergent pPCI.

Methods

Using the ACTION Registry‐GWTG, we evaluated the impact of RIPC applied during inter‐facility helicopter transport of STEMI patients from non‐PCI capable hospitals to 2 PCI‐hospitals in the United States between March, 2013 and September, 2015 on the incidence of AKI following pPCI. AKI was defined as ≥0.3 mg/dL increase in creatinine within 48–72 hours after pPCI.

Results

Patients who received RIPC (n = 127), compared to those who did not (n = 92), were less likely to have AKI (11 of 127 patients [8.7%] vs. 17 of 92 patients [18.5%]; adjusted odds ratio = 0.32, 95% CI 0.12–0.85, P = 0.023) and all‐cause in‐hospital mortality (2 of 127 patients [1.6%] vs. 7 of 92 patients [7.6%]; adjusted odds ratio = 0.14, 95% CI 0.02–0.86, P = 0.034) after adjusting for socio‐demographic and clinical characteristics. There was no difference in hospital length of stay (3 days [interquartile range, 2–4] vs. 3 days [interquartile range, 2–5], P = 0.357) between the 2 groups.

Conclusion

RIPC applied during inter‐facility helicopter transport of STEMI patients for pPCI is associated with lower incidence of AKI and in‐hospital mortality. The use of RIPC for renal protection in STEMI patients warrants further in depth investigation.

     

Efficacy and safety of optimized antithrombotic therapy with aspirin, clopidogrel and enoxaparin in patients with non-ST segment elevation acute coronary syndromes in clinical practice

In randomized clinical trials enoxaparin in non ST-elevation acute coronary syndromes (NSTE-ACS) has been shown to be more effective than unfractionated heparin in preventing the combined endpoint of death and myocardial infarction. Clopidogrel in combination with aspirin reduced the combined endpoint of death, myocardial infarction and stroke in NSTE-ACS patients compared to aspirin alone. Aim of the present study was to determine the clinical impact of optimized antithrombotic therapy with enoxaparin, clopidogrel and aspirin compared to standard therapy with unfractionated heparin (UFH) and aspirin in NSTE-ACS in clinical practice. We analyzed data of 2,956 consecutive patients with NSTE-ACS and either antithrombotic therapy with enoxaparin, clopidogrel and aspirin or with aspirin and UFH, which were prospectively enrolled in the acute coronary syndromes registry (ACOS) from July 2000 until the end of November 2002. After adjustment for baseline characteristics and PCI the combined endpoint of hospital death and non-fatal reinfarctions was lower in the group with optimized antithrombotic therapy including clopidogrel, enoxaparin and aspirin compared to the control-group with aspirin and UFH (odds ratio 0.30, 95% confidence interval 0.16–0.53). There was no significant difference in major bleedings between the two treatment groups (1.5% vs. 0.9%, P = 0.35), while overall there were more bleeding complications in the group with optimized antithrombotic therapy (4.9% vs. 2.0%, P = 0.005). In clinical practice optimized antithrombotic therapy with aspirin, clopidogrel and enoxaparin in NSTE-ACS is associated with a reduction in the combined endpoint of death and non-fatal reinfarctions compared to standard therapy with aspirin and UFH without increase in major bleeding complications.     

Impact of anticoagulation regimens on sheath management and bleeding in patients undergoing elective percutaneous coronary intervention in the STEEPLE trial

Objective: To evaluate the impact of sheath management on bleeding rates. Background: The procedural characteristics and anticoagulant regimen determine the frequency of postoperative bleeding complications following percutaneous coronary intervention (PCI). Methods: This subanalysis of the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial evaluated the relative impact of enoxaparin or unfractionated heparin (UFH) on the rate of non‐coronary artery bypass graft‐related major and minor bleeding, according to sheath management procedures in 3,528 patients undergoing elective PCI with a femoral approach. Results: Sheaths were removed at a median time of 54 min with enoxaparin 0.5 mg/kg, compared with 3 hr 14 min with enoxaparin 0.75 mg/kg and 2 hr 24 min with UFH. Early sheath removal (within 30 min from the end of PCI) was associated with reduced bleeding in patients receiving 0.5 or 0.75 mg/kg enoxaparin compared with UFH (enoxaparin 0.5 mg/kg: 4.9% vs. 10.8%; P < 0.001; enoxaparin 0.75 mg/kg: 5.0% vs. 10.8%; P < 0.001). Compared with UFH, major and minor bleeding was halved when enoxaparin (0.5 mg/kg and 0.75 mg/kg) was used in combination with a closure device (4.4% and 5.3% vs. 10.5% with UFH) or smaller (<7 Fr) sheath sizes (4.9% and 6.0% vs. 9.3%). Conclusion: This analysis shows that early sheath removal can be performed safely following elective PCI in patients receiving enoxaparin. Enoxaparin use was associated with less major and minor bleeding compared with UFH, when either a closure device or a smaller sheath size was used. © 2009 Wiley‐Liss, Inc.     

Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction.

AIMS: To compare the efficacy and safety of low molecular weight heparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. METHODS AND RESULTS: Three-hundred patients receiving fibrinolytic therapy following acute myocardial infarction were randomly assigned to low molecular weight heparin as enoxaparin (40 mg intravenous bolus, then 40 mg subcutaneously every 8 h, n=149) or unfractionated heparin (5000 U intravenous bolus, then 30 000 U. 24 h(-1), adjusted to an activated partial thromboplastin time 2-2.5x normal, n=151) for 4 days in conjunction with routine therapy. Clinical and therapeutic variables were analysed, in addition to use of enoxaparin or unfractionated heparin, to determine independent predictors of the 90-day composite triple end-point (death, non-fatal reinfarction, or readmission with unstable angina). The triple end-point occurred more frequently in patients receiving unfractionated heparin rather than enoxaparin (36% vs. 26%; P=0.04). Logistic regression modelling of baseline and clinical variables identified the only independent risk factors for recurrent events as left ventricular failure, hypertension, and use of unfractionated heparin rather than enoxaparin. There was no difference in major haemorrhage between those receiving enoxaparin (3%) and unfractionated heparin (4%). CONCLUSION: Use of enoxaparin compared with unfractionated heparin in patients receiving fibrinolytic therapy for acute myocardial infarction was associated with fewer recurrent cardiac events at 90 days. This benefit was independent of other important clinical and therapeutic factors.     

The ratio of contrast volume to glomerular filtration rate predicts outcomes after percutaneous coronary intervention for ST‐segment elevation acute myocardial infarction

Objective: To assess the value of the ratio between contrast medium volume and glomerular filtration rate (CMGFRr) for prediction of development of contrast‐induced nephropathy (CIN) and mortality in patients with ST‐segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Background: Renal function is a strong predictor of outcome in patients with STEMI. CIN may complicate the course of primary PCI in these patients. Methods: The study population included all 871 consecutive patients with STEMI without cardiogenic shock who underwent primary PCI at our center from January 1, 2001, to October 30, 2006. CIN was defined as an absolute increase in serum creatinine > 0.5 mg/dL or a relative increase >25% within 48 hr after PCI. Results: In‐hospital CIN developed in 72 (8.3%) patients. On linear regression analysis, the following variables were independently associated with CIN: male sex (odds ratio [OR] = 0.42, 95% confidence interval [CI], 0.18–0.97, P = 0.04), GFR < 60 (OR = 3.6, 95% CI, 2.79–4.78, P < 0.0001), multivessel coronary artery disease (OR = 1.67, 95% CI, 1.08–2.58, P = 0.02), CMGFRr (OR = 1.53, 95% CI, 1.01–2.31, P = 0.04, for upper tertile vs. lower two tertiles), and Killip class > 1 (OR = 1.35, 95% CI, 1.03–1.76, P = 0.03). CMGFRr > 3.7 was a strong independent predictor of CIN (OR = 3.87, 95% CI, 1.72–8.68, P = 0.001). Twenty‐six (2.9%) patients died at 1 month after PCI. The following variables were independently predictive of 1‐month mortality: CMGFRr > 3.7 (OR = 3.3, 95% CI, 1.22–9.04, P = 0.018) and multivessel coronary artery disease (OR = 2.3, 95% CI, 1.28–4.07, P = 0.005). Conclusion: The contrast medium‐to‐GFR ratio is a strong predictor of CIN and of 1‐month mortality in patients undergoing primary PCI for STEMI. © 2010 Wiley‐Liss, Inc.     

Meta-analysis comparing bivalirudin versus heparin monotherapy on ischemic and bleeding outcomes after percutaneous coronary intervention

With femoral access, bivalirudin decreases risks of major bleeding after percutaneous coronary intervention (PCI) and provides better net clinical benefit compared to unfractionated heparin (UFH) plus planned glycoprotein IIb/IIIa inhibitors. Whether this benefit exists compared to UFH monotherapy is less clear. We performed a systematic review and meta-analysis to compare outcomes in patients undergoing transfemoral PCI with UFH or bivalirudin. Randomized trials (n = 3) and observational studies (n = 13) comparing bivalirudin to UFH monotherapy were reviewed. Primary outcomes were 30-day rates of major adverse cardiovascular events (MACEs) including death, myocardial infarction (MI), urgent revascularization, as well as all-cause mortality, MI, major bleeding, and blood transfusion. We collected data from 16 studies involving 32,492 patients undergoing PCI. Most observational studies were performed in the United States, whereas all randomized trials were done in Europe. Compared to UFH monotherapy, bivalirudin was associated with similar risk of MACEs (odds ratios [OR] 0.92, 95% confidence interval [CI] 0.75 to 1.12), a substantial 45% relative decrease in major bleeding (OR 0.55, 95% CI 0.43 to 0.72), and a trend in the decrease of transfusion (OR 0.87, 95% CI 0.70 to 1.08). A decrease in mortality was seen in observational studies (OR 0.62, 95% CI 0.45 to 0.85) but remained inconclusive in randomized trials (OR 0.63, 95% CI 0.20 to 2.01). MI rate was similar with the 2 anticoagulants. In conclusion, in patients undergoing transfemoral PCI, the benefit of bivalirudin over UFH monotherapy is driven by a significant decrease in major bleeding with similar rates of MACE. As PCI practice moves toward other bleeding-avoidance strategies such as the radial approach, future studies should focus on the interaction between anticoagulant strategy and access-site choice.     

Early and mid-term clinical outcome of emergency PCI in patients with STEMI due to unprotected left main coronary artery disease

Objectives: Evaluation of acute and mid‐term outcomes of patients with ST‐elevation myocardial infarction (STEMI) undergoing emergency PCI due to unprotected left main coronary artery (ULMCA) disease. Background: STEMI patients due to ULMCA disease represent a rare, high risk group. Percutaneous coronary intervention (PCI) may be the preferred strategy of myocardial revascularization but there are few data about this topic. Methods: We analyzed 30‐day and mid‐term mortality of 58 patients with STEMI and ULMCA disease as culprit lesion treated in our centre by emergency PCI between 2000 to 2010. Results: Mean age was 67.3 ± 11.5 years. Thirty (51.7%) patients had cardiogenic shock on admission. PCI success was achieved in 54 patients (93.1%). Mean follow‐up was 15.8 ± 10.9 months (median 14, range 6–45). Thirty‐day and mid‐term mortality rates were 39.7% and 44%. Backward binary logistic regression model identified cardiogenic shock at presentation (OR 12.6, 95% CI 2.97–53.6, P < 0.001), age ≥75 years (OR 5.9, 95% CI 1.3–26.5, P = 0.019) and post‐PCI TIMI flow grade <3 (OR 2.9, 95% CI 1.8–5.7 P = 0.02) as independent predictors of 30‐day mortality. Cox proportional hazard ratio (HR) identified shock at presentation (HR 5.2, 95% CI 1.8–14.3, P < 0.002), age ≥75 years (HR 3.9, 95% CI 1.8–8.7, P < 0.001), post‐PCI TIMI flow grade <3 (HR 4.9, 95% CI 1.6–14.6; P < 0.005) as independent predictors of mid‐term mortality. Conclusions: In patients with STEMI and ULMCA as culprit lesion, emergency PCI is a valuable therapeutic strategy. Early and mid‐term survival depends on cardiogenic shock, advanced age, and PCI failure. Patients surviving the first month have good mid‐term prognosis. (J Interven Cardiol 2012;25:215–222)     

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.     

Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial.

OBJECTIVES: This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. BACKGROUND: In the OASIS-5 trial, fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%. METHODS: The OASIS-5 trial was a double-blind, randomized comparison of fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the fondaparinux group, intravenous fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was <6 h from last subcutaneous dose, and additional intravenous unfractionated heparin (UFH) was given if PCI was >6 h. RESULTS: Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p < 0.00001) at day 9, with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Fondaparinux reduced major bleeding 48 h after PCI irrespective of whether PCI was performed <6 h of the last enoxaparin dose (1.6% vs. 3.8%, HR 0.42, p < 0.0001) or >6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p < 0.0001). Catheter thrombus was more common in patients receiving fondaparinux (0.9%) than enoxaparin alone (0.4%), but was largely prevented by using UFH at the time of PCI, without any increase in bleeding. CONCLUSIONS: Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream fondaparinux.     

Percutaneous Coronary Intervention,Comorbidities, and Mortality among Emergency Department–Admitted ST‐Elevation Myocardial Infarction Patients in Florida

Background: Risk of mortality following an ST‐elevation myocardial infarction (STEMI) can be significantly reduced by prompt percutaneous coronary intervention (PCI). National guidelines specify primary PCI as the preferred recommended treatment for STEMI. In this study, we examined same‐day PCI as an independent predictor of in‐hospital mortality, after adjustment for comorbidities, other patient factors, and hospital PCI‐volume using unselected surveillance data from Florida. Methods: We analyzed hospital discharge data for adults, 18+ years old, with a primary diagnosis of STEMI who were admitted to PCI‐capable hospitals through the emergency department during 2001–2005 (n = 43,849). Hierarchical (multilevel) logistic regression models were used for analysis. Results: Overall, 4,143 STEMI patients (9.4%) did not survive to hospital discharge. In late 2005, the in‐hospital mortality rates were 1.9% for those who received same‐day PCI versus 13.0% for those who did not. After adjustment for multiple patient factors, same‐day PCI was a significant predictor of in‐hospital survival with a strong protective effect (adjusted OR = 0.35, 95% CI 0.31–0.38 P < 0.0001). Restriction of the analysis to those patients who survived the first day of admission did not appreciably change this result (adjust OR = 0.37, 95% CI 0.33–0.42, P < 0.0001). Hospital PCI‐volume did not significantly impact mortality risk. Conclusions: Same‐day PCI markedly reduced the risk of in‐hospital mortality among STEMI patients after multivariate adjustment. Serious comorbidities and complications, older age, and female gender continued to predict elevated risk of mortality after control for treatment status. Our results provide additional evidence in support of national clinical recommendations and aggressive treatment of STEMI. (J Interven Cardiol 2010;23:205–215)     

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.