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.     

Improved clinical outcomes with abciximab therapy in acute myocardial infarction: a systematic overview of randomized clinical trials

Background

Investigations of glycoprotein (GP) IIb/IIIa inhibition in primary percutaneous coronary intervention (PCI) have suggested the efficacy of abciximab in improving clinical and angiographic outcomes, but sample-size limitations and variability in trial design preclude the ability to generalize these results to a broader patient population.

Methods

Meta-analytic techniques were used to evaluate clinical outcomes from randomized trials comparing GP IIb/IIIa inhibition with placebo or control therapy in primary PCI for acute myocardial infarction (MI).

Results

In 3266 patients, treatment with abciximab significantly reduced the 30-day composite end point of death, reinfarction, or ischemic or urgent target-vessel revascularization (TVR; odds ratio [OR], 0.54; 95% CI, 0.40-0.72), with trends toward reduced 30-day death and death or reinfarction. Abciximab resulted in an increased likelihood of major bleeding (OR, 1.74; 95% CI, 1.11-2.72). By 6 months, abciximab significantly reduced the occurrence of death, reinfarction, or any TVR (OR, 0.80; 95% CI, 0.67-0.97), and there were positive trends favoring a decrease in mortality alone and the composite of death or reinfarction.

Conclusions

Treatment with abciximab significantly reduces early adverse ischemic events, a clinical benefit that is maintained at 6-month follow-up. These findings support the use of adjunctive GP IIb/IIIa inhibition in primary PCI.     

Subcutaneous enoxaparin with early invasive strategy in patients with acute coronary syndromes

Background

Subcutaneous enoxaparin during at least 48 hours provides adequate anticoagulation and good clinical results in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI).

Methods

In this nonrandomized retrospective study, we compared 347 patients with non-ST-segment elevation acute coronary syndromes who underwent rapid PCI after only 2 injections of subcutaneous enoxaparin (EI, n = 117) to those referred later to the catheterization laboratory with ≥3 injections (DI, n = 230). We measured anti-Xa at the time of PCI and evaluated bleeding and major ischemic events (death/myocardial infarction) at 30 days.

Results

Patients in the EI group more frequently received glycoprotein IIb/IIIa inhibitors and clopidogrel preceding PCI than did patients in the DI group (58.1% vs 31.7%, P < .0001 for glycoprotein IIb/IIIa inhibitors and 68.4% vs 40.4% for clopidogrel pretreatment, P < .0001, respectively). The anti-Xa activity measured at the time of catheterization (0.92 ± 0.04 U/mL vs 0.96 ± 0.02 U/mL, EI vs DI, P = .25) and the injection-to-catheterization times (5.6 ± 0.2 h vs 5.2 ± 0.1 h, EI vs DI, P = .17) were similar in both groups. The 30-day bleeding rates of 1.7% and 4.8% in the EI and DI strategies were found to be equivalent with a significant non-inferiority test for the EI strategy (P < .05). There was a nonsignificant trend for less death or myocardial infarction at 30 days in the EI group compared to the DI group (4.3% vs 7.0%, non-inferiority test not significant).

Conclusion

A rapid invasive strategy with only 2 subcutaneous injections of enoxaparin provides similar levels of anticoagulation, and is associated with a favorable trend for ischemic events and with safety equivalent to a more prolonged “upstream” treatment with enoxaparin.     

Elective percutaneous coronary intervention using broad-spectrum antiplatelet therapy (eptifibatide, clopidogrel, and aspirin) alone, without scheduled unfractionated heparin or other antithrombin therapy

Background

Adjunctive pharmacotherapy during percutaneous coronary intervention (PCI) has historically consisted of a regimen of antiplatelet agents accompanied by an antithrombin agent, typically unfractionated heparin. Paradoxically, unfractionated heparin may activate platelets, induce other pro-thrombotic activities, increase bleeding complications, and cause thrombocytopenia. To optimize patient care and avoid the potential risks of unfractionated heparin in patients undergoing elective PCI, one of the authors began to use adjunctive pharmacotherapy consisting of broad-spectrum antiplatelet therapy alone, without scheduled unfractionated heparin or other antithrombin therapy.

Methods

Five hundred consecutive patients undergoing scheduled, elective PCI (stent deployment, cutting balloon atherotomy, conventional balloon angioplasty, or high-speed rotational atherectomy) received adjunctive pharmacotherapy consisting of eptifibatide, clopidogrel, and aspirin.

Results

The technical success rate was 100%. During the first 24 hours, there were no major adverse clinical events. Non-Q-wave myocardial infarction occurred in 1.6% of patients, major and minor bleeding complications in 0.2% and 0.6%, respectively, and thrombocytopenia in 0.6%. During the first 30 days, there was 1 (0.2%) major adverse clinical event.

Conclusions

For elective PCI, adjunctive pharmacotherapy consisting of broad-spectrum antiplatelet therapy alone, without scheduled unfractionated heparin or other antithrombin therapy, appears to be safe and may prove to be efficacious.     

Platelet activation after stenting with heparin-coated versus noncoated stents

Background

In animal models, heparin coating reduces platelet accumulation induced by coronary stenting. However, reduced platelet activation has never been demonstrated in humans. The purpose of the current study was to investigate the effect of heparin coating on platelet activation after coronary artery stenting.

Methods

In a prospective, randomized, pilot study of 50 consecutive elective patients, platelet activation was analyzed by measuring aggregation and surface receptor expression before and at 2 hours, 24 hours, 5 days and 30 days after implantation of either heparin-coated or noncoated stents .

Results

There was less platelet activation after implantation of a heparin-coated stent, as indicated by reduced expression at 24 hours of active glycoprotein (GP) IIb/IIIa (10.3 ± 6.1 vs 6.7 ± 2.1, P = .014), and total GP IIb/IIIa (382 ± 101 vs 306 ± 88, P = .01). A trend at 30 days poststenting of lower total (383 ± 150 vs 296 ± 86, P = .07) and active GP IIb/IIIa expression (10.3 ± 6.9 vs 7.5 ± 2.9, P = .15) was also observed with the heparin-coated stent). Aggregation and stimulated p-selectin did not differ between stent types.

Conclusion

Use of a heparin-coated stent in this pilot study of elective patients was associated with primarily less early platelet expression of GP IIb/IIIa. These findings have implications on the risk of subacute thrombosis and deserve further investigation.     

Bleeding events with abciximab in acute coronary syndromes without early revascularization: An analysis of GUSTO IV-ACS

Background

The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates.

Methods

In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure.

Results

In 1507 patients (19.3%), bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) classification was observed while they were hospitalized or within 7 days. Ninety-eight patients (1.2%) had a major bleed, including 8 with intracranial hemorrhages. In 215 patients (2.8%), a minor bleed was reported, and in 1194 patients (15.3%), an insignificant bleed was reported. Bleeding was more frequent in patients receiving a 48-hour infusion of abciximab. Spontaneous bleeding was seen in 911 patients (11.7%). The other 596 patients had a bleeding event in conjunction with a procedure. The most significant predictors for bleeding with multivariable analysis were: use of low-molecular weight heparin, duration of abciximab infusion, region of hospitalization, performance of coronary artery bypass grafting or percutaneous coronary intervention (PCI), advanced age, and female sex. For major bleeding, the predictors were performance of coronary artery bypass grafting or PCI, long duration of abciximab administration, and advanced age.

Conclusion

Treatment with abciximab in patients with non-ST-elevation acute coronary syndromes is safe because major bleeding and stroke are rare, and most events are clinically manageable or have few clinical consequences. Guidelines for use of abciximab in combination with other antithrombotic agents developed for PCI should also be respected in acute coronary syndromes. Specific dosing guidelines for combination with low-molecular weight heparin must be developed for patients who subsequently will undergo a PCI.     

Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: a report from the NHLBI Dynamic Registry

Background

Older age has been associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). As PCI technology evolves and the US population becomes proportionally older, assessment of PCI in older age groups is essential.

Methods

From the National Heart, Lung, and Blood Institute Dynamic Registry, 4620 PCI-treated patients (1997 to 1999) were studied. Differences in clinical presentation, treatment strategy, and inhospital and 1-year outcomes were compared between patient age groups: younger (<65 years, n = 2537); older (65 to 79 years, n = 1776); and elderly (≥80 years, n = 307).

Results

Older and elderly patients had more cardiac and comorbid noncardiac conditions and more extensive and complex arteriosclerosis, including stenoses in bypass grafts. Stent use was similar as age increased (72% vs 73% vs 73%), as was the use of IIb/IIIa receptor antagonists (29% vs 26% vs 28%). Rates of successful treatment of all attempted lesions were 93%, 92%, and 89%, respectively. Adjusted relative risks of inhospital death (1.0 vs 2.91 vs 3.64) and myocardial infarction (1.0 vs 1.35 vs 2.57) increased by age group, as did 1-year mortality rates (1.0 vs 1.87 vs 3.02). However, the relative magnitude of excess mortality rates at 1 year was comparable to that observed by age in the US general population. Age was not associated with 1-year risk of myocardial infarction or coronary artery bypass grafting.

Conclusions

Although new technologies may allow for treatment of complex disease in older and elderly patients with comorbid disease, the increased procedural risk remains substantial in these patients. After PCI, the long-term relative risk of death is similar to that expected among persons of similar ages in the general population.     

Antithrombotic therapy in the acute phase of unstable angina

Low molecular weight heparins appear to be a better choice in patients with unstable angina than unfractionated heparin. In addition, the excellent predictable dose-response makes them suitable to prevent ischemic complications of percutaneous coronary intervention. Although direct comparisons between LMWH and UH are limited, substantial evidence exists that patients receiving LMWH can be safely brought to cardiac catheterization. Therefore, previous concern regarding transitioning such therapy from the medical service to the cardiac catheterization laboratory should not impede the upstream use of thèse agents. Although UH remains an option in conjunction with GP IIB/IIIa inhibitors, there is substantial evidence that LMWH and GP IIb/IIIa inhibitor therapy can be used safely in combination. Although GP IIb/IIIa inhibitors are very potent to prevent ischemic events after percutaneous coronary interventions, their benefit in the medical management of unstable angina is much more modest. ADP receptor antagonists reduce major ischemic events in combination with aspirin in the medical management of unstable angina patients but also when PCI is planned. Their combination with GP IIB/IIIa receptor antagonist does not impair the benefit of GP IIb/IIIa antagonists. The development of biologic tools to monitor these antithrombotic regimen is highly warranted especially in high risk patients (chronic renal failure, elderly).     

What is the role for improved long-term antiplatelet therapy after percutaneous coronary intervention?

Background

Coronary stent placement has replaced balloon angioplasty as the percutaneous coronary intervention (PCI) method of choice, primarily because of its lower restenosis rate. Compared with aspirin (ASA) monotherapy or ASA plus warfarin, the ticlopidine and ASA combination is superior in reducing thrombotic events after stenting. Clopidogrel plus ASA appears to be at least as effective as ticlopidine and ASA. Intravenous glycoprotein IIb/IIIa inhibitors effectively prevent periprocedural thrombotic complications, but their short duration of action and parenteral dosing don’t allow for long-term protection. This review aimed to answer how long after PCI with a stent patients are at risk for recurrent thrombotic events and what the optimal way to prevent them is.

Results

Classically, ASA has been prescribed indefinitely, whereas adenosine diphosphate receptor antagonists have been discontinued after 2 to 4 weeks. However, the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial found that long-term dual antiplatelet therapy with clopidogrel and ASA was more effective than ASA alone in preventing major cardiovascular events in patients with acute coronary syndrome, including those treated with PCI.

Conclusion

Results from additional ongoing studies are needed to clarify the role of long-term dual oral antiplatelet therapy in preventing ischemic events in patients who have undergone PCI.     

Combination Enoxaparin and Abciximab During Percutaneous Coronary Intervention: A New Standard of Care?

Evidence from randomized trials supports the administration of platelet glycoprotein (GP) IIb/IIIa blockade both to patients undergoing percutaneous coronary intervention (PCI) and those presenting with non-ST elevation acute coronary syndromes (ACSs). Similarly, the low molecular weight heparin (LMWH), enoxaparin, has demonstrated superior efficacy when compared with unfractionated heparin (UFH) in the treatment of patients with non-ST elevation ACS. Algorithms for seamless integration of pharmacotherpy through the course of hospitalization for patients who present with ACS and who require PCI will likely combine therapy with enoxaparin and platelet GP IIb/IIIa blockade (abciximab). Our preliminary experience with combination enoxaparin and abciximab as adjunctive pharmacotherapy for PCI suggests that this strategy is safe and effective and may offer advantages over a conventional strategy, which employs UFH.     

Effects of clopidogrel and aspirin combination versus aspirin alone on platelet aggregation and major receptor expression in patients with heart failure: the Plavix Use for Treatment Of Congestive Heart Failure (PLUTO-CHF) trial

Background

Persistent platelet activation may contribute to thrombotic events in patients with congestive heart failure (CHF). Chronic use of mild platelet inhibitors could therefore represent an independent avenue to improve morbidity, mortality, and quality of life in this expanding population. Although clopidogrel is widely used in patients with acute coronary syndromes and ischemic stroke, the ability of this novel ADP-receptor antagonist to inhibit platelet function in patients with CHF is unknown. We assessed antiplatelet properties of clopidogrel with aspirin (C+A) versus aspirin alone (A) in patients with CHF with heightened platelet activity.

Methods

Patients with left ventricular ejection fraction <40%, or CHF symptoms in the setting of preserved systolic function and New York Heart Association class II-IV were screened. Patients were considered to have platelet activation when 4 of the following 5 parameters were met: ADP-induced platelet aggregation >60%; collagen-induced aggregation >70%; whole blood aggregation >18 ohms; expression of GP IIb/IIIa >220 log MFI; and P-selectin cell positivity >8%. All patients were treated with 325 mg of acetylsalycilic acid (ASA) for at least 1 month. Patients receiving an antithrombotic agent other than ASA were excluded. Patients meeting clinical and laboratory criteria were randomly assigned to C+A (n=25), A (n=25) groups, or represent screen failures (n=38). Platelet studies (conventional and whole blood aggregometry, shear-induced activation, expression of 10 major receptors and formation of platelet-leukocyte microparticles) were performed at baseline and after 30 days of therapy.

Results

There were no deaths, hospitalizations, or serious adverse events. There were no changes in platelet parameters in the A group. In contrast, therapy with C+A resulted in a significant inhibition of platelet activity assessed by ADP-induced (P = .00001), and epinephrine-induced (P = .0016) aggregation, closure time (P = .04), expression of PECAM-1 (P = .009), GP Ib (P = .006), GP IIb/IIIa antigen (P = .0001), GP IIb/IIIa activity with PAC-1 (P = .0021), and CD151 (P = .0026) when compared with the A group. Therapy with C+A also resulted in the reduced formation of platelet-leukocyte microparticles (P = .021). Collagen-induced aggregation in plasma and in whole blood, expression of vitronectin receptor, P-selectin, CD63, CD107a, and CD107b did not differ among groups.

Conclusions

Treatment with C+A for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients with CHF. Patients with CHF with heightened platelet activity represent a potential target population in which addition of clopidogrel may decrease mortality rates by reducing the incidence of thrombotic vascular events.     

Association of the PURSUIT risk score with predischarge ejection fraction, angiographic severity of coronary artery disease, and mortality in a nonselected, community-based population with non-ST-elevation acute myocardial infarction

Background

The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) risk score was derived from the PURSUIT trial population for 30-day mortality prediction.

Methods

The PURSUIT risk score was calculated for 337 consecutive Olmsted County residents with non-ST-elevation acute myocardial infarction admitted to the coronary care unit of our institution from 1988 through 1998. Predischarge ejection fraction (EF) measurement was available for 246 patients (73%). After excluding patients with prior coronary artery bypass graft surgery (n = 42), 219 patients (65%) had coronary angiography within 30 days of admission. Mortality at 30 days was 8.9%. Among 30-day survivors, mortality at 1 year was 7.9%.

Results

Mean age was 70 ± 13 years, and 37% of patients were women. Mean predischarge EF was 52% ± 16%. Patients with higher PURSUIT risk score had lower EF (P < .001). Three-vessel (≥70% stenosis in all 3 coronary arteries) or left main (≥50% stenosis) coronary artery disease was present in 60 of 219 patients (27%) who had coronary angiography. Higher PURSUIT risk score was associated with greater likelihood of 3-vessel or left main disease (P < .001). The PURSUIT risk score had very good predictive accuracy for both early (30-day, C-statistic = 0.78) and late (30-day to 1-year, C-statistic = 0.77) mortality.

Conclusions

The PURSUIT risk score correlates with EF, angiographic severity of coronary artery disease, and short- and long-term mortality of nonselected patients with non-ST-elevation acute myocardial infarction.     

Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy)

Background

It has been expected that therapy with oral glycoprotein (GP) IIb/IIIa blockers including roxifiban will reduce mortality and vascular complications in a long-term. However, platelet-related properties of roxifiban in the clinical setting are not well known. We measured platelet characteristics during chronic treatment in patients with coronary artery disease enrolled in the Roxifiban Oral Compound Kinetics Evaluation Trial (ROCKET-I).

Methods

ROCKET-I was designed as a randomized, double blind, multicenter, dose-ranging study of roxifiban, administered either as monotherapy or concomitantly with aspirin, compared with aspirin alone. Thirty-one patients were assigned for 24 weeks of therapy with aspirin (n = 7), roxifiban (n = 9), or roxifiban plus aspirin (n = 15). Platelets were assessed 5 times in each patient at baseline, and at weeks 2, 4, 12, 18, and 24 thereafter with aggregometry and flow cytometry.

Results

Baseline platelet characteristics were similar in all 3 groups. There was a consistent significant decrease of adenosine diphosphate- (P = .0001) and collagen-induced (P = .002) platelet aggregation in the patients treated with roxifiban when compared with patients treated with aspirin alone. Flow cytometry revealed paradoxical late activation of GP IIb/IIIa expression (P = .007) when roxifiban was used without aspirin, which was significant compared with the aspirin and aspirin-roxifiban groups. There were no differences among groups in GP Ib expression, although its rise was more profound in the patients treated with roxifiban. There were substantial differences in the P-selectin expression. Although aspirin time dependently decreased the percent of P-selectin positive platelets (P = .02), treatment with roxifiban resulted in the phasic changes with the early inhibition (P = .01) and then 2-fold activation (P = .0001) starting at week 12 of the therapy. There was an early transient activation of platelet endothelial cell adhesion molecule-1 expression (P = .008) at week 2, followed by the later inhibition of this receptor (P = .003) in patients treated with roxifiban.

Conclusion

Despite achieving sustained inhibition of platelet aggregation, therapy with roxifiban has been associated with over expression or phasic changes of major platelet receptors. These data may explain clinical concerns about the use of oral GP IIb/IIIa inhibitors linking higher mortality rates and incidence of thrombotic episodes with paradoxical switching to alternative passways of platelet activation.     

Adherence to Pharmacological Thromboprophylaxis Orders in Hospitalized Patients

Objective

We compared adherence to unfractionated heparin (UFH) 2 or 3 times daily prophylaxis orders versus low-molecular-weight heparin (LMWH) once daily orders. Our goals were to determine which strategy demonstrated the best adherence in terms of timing and frequency of dose administration, and to determine reasons for ordered heparin not being administered.

Methods

We queried our electronic medication administration record where nurses document reasons for delayed administration or omitted doses. We identified 250 consecutive patients who were prescribed prophylaxis with UFH 2 or 3 times daily or LMWH once daily. We followed patients for their hospitalization to determine adherence to physicians' prophylaxis orders.

Results

Adherence, defined as the ratio of prophylaxis doses given to doses ordered, was greater with LMWH (94.9%) than UFH 3 times daily (87.8%) or UFH twice daily (86.8%) regimens (P <.001). Patients receiving LMWH more often received all of their scheduled prophylaxis doses (77%) versus UFH 3 times daily (54%) or UFH twice daily (45%) (P <.001). There were no differences between regimens regarding reasons for omitted doses. The most common reason for late or omitted doses was patient refusal, which explained 44% of the UFH and 39% of the LMWH orders that were not administered.

Conclusions

LMWH once a day had better adherence than UFH 2 or 3 times daily. For both LMWH and UFH, patient refusal was the most common reason for not administering prophylaxis as prescribed. These findings require consideration when evaluating pharmacological prophylaxis strategies. Educational programs, explaining the rationale, may motivate patients to improve adherence during hospitalization.     

Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial: study design and rationale

Background

Patients with acute coronary syndromes (ACS; unstable angina and non-ST-segment elevation myocardial infarction) are at significant risk for death and myocardial infarction. Early angiography followed by revascularization is considered the treatment of choice for moderate- to high-risk patients with ACS. However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors, and thienopyridines, the rate of adverse ischemic events still remains unacceptably high, and the intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty and surgical revascularization procedures elicit a high rate of bleeding complications. Pilot trials suggest that the thrombin-specific anticoagulant bivalirudin may improve clinical outcomes in ACS.

Study design

In the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial, 13,800 patients with moderate- to high-risk ACS are being prospectively randomly assigned at up to 600 centers to unfractionated heparin or enoxaparin + IIb/IIIa inhibition, versus bivalirudin + IIb/IIIa inhibition, versus bivalirudin + provisional IIb/IIIa inhibition. All patients undergo cardiac catheterization within 72 hours, followed by percutaneous or surgical revascularization when appropriate. In a second random assignment, patients assigned to receive IIb/IIIa inhibitors are subrandomized to upstream drug initiation, versus IIb/IIIa inhibitor administration during angioplasty only. The primary study end point is the composite of death, myocardial infarction, unplanned revascularization for ischemia, and major bleeding at 30 days. Clinical follow-up will continue for 1 year.

Conclusions

The ACUITY trial is the largest study yet performed in patients with ACS undergoing an invasive strategy. In addition to evaluating the utility of bivalirudin in ACS, this study will also provide important guidance regarding the necessity for and timing of IIb/IIIa inhibitor administration.     

The combination of enoxaparin, glycoprotein IIb/IIIa inhibitors and an early invasive approach among acute coronary syndrome patients

OBJECTIVES: This study was designed to assess the feasibility and safety of enoxaparin in combination with glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) as part of an early invasive strategy in patients presenting with acute coronary syndromes (ACS). BACKGROUND: Trials in patients with ACS have evaluated the utility of enoxaparin, adjuvant GP IIb/IIIa inhibitors with PCI, and an early invasive approach. Information about the combination of all three of these approaches, however, is limited. METHODS: Forty-nine patients with ACS underwent cardiac catheterization, of whom 23 underwent PCI with enoxaparin and GP IIb/IIIa inhibitors. RESULTS: The primary endpoint of the study, a composite of death, myocardial infarction or urgent revascularization at 30 days, occurred in 8% of patients undergoing PCI. There were no deaths. One patient received a blood transfusion. No other adverse events occurred. These event rates were comparable to those from the pooled EPILOG/EPISTENT database, in which intravenous unfractionated heparin was used in conjunction with GP IIb/IIIa receptor blockade. The mean anti-Xa level in patients undergoing PCI was 0.74 0.48 U/ml. The majority of patients who underwent PCI within eight hours of their last dose of enoxaparin had therapeutic anti-Xa levels. CONCLUSION: In patients with ACS, enoxaparin in combination with GP IIb/IIIa inhibitors and an early invasive approach resulted in comparable clinical complication and bleeding rates versus historical references utilizing unfractionated heparin.     

Warfarin Use and Outcomes in Patients with Atrial Fibrillation Complicating Acute Coronary Syndromes

Background

We examined warfarin use at discharge (according to Congestive heart failure, Hypertension, Age > 75 years, Diabetes, Prior Stroke/transient ischemic attack score and bleeding risk) and its association with 6-month death or myocardial infarction in patients with post-acute coronary syndrome atrial fibrillation.

Methods

Of the 23,208 patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network A, and Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors trials, 4.0% (917 patients) had atrial fibrillation as an in-hospital complication and were discharged alive. Cox proportional hazards models were performed to assess 6-month outcomes after discharge.

Results

Overall, 13.5% of patients with an acute coronary syndrome complicated by atrial fibrillation received warfarin at discharge. Warfarin use among patients with atrial fibrillation had no relation with estimated stroke risk; similar rates were observed across Congestive heart failure, Hypertension, Age > 75 years, Diabetes, Prior Stroke/transient ischemic attack (CHADS₂) scores (0, 13%; 1, 14%; ≥ 2, 13%) and across different bleeding risk categories (low risk, 11.9%; intermediate risk, 13.3%; high risk, 11.1%). Among patients with in-hospital atrial fibrillation, warfarin use at discharge was independently associated with a lower risk of death or myocardial infarction within 6 months of discharge (hazard ratio 0.39; 95% confidence interval, 0.15-0.98).

Conclusion

Warfarin is associated with better 6-month outcomes among patients with atrial fibrillation complicating an acute coronary syndrome, but its use is not related to CHADS₂ score or bleeding risk.     

The activated clotting time (ACT) can be used to monitor enoxaparin and dalteparin after intravenous administration

BACKGROUND: The use of low-molecular weight heparin (LMWH) during percutaneous coronary intervention (PCI) has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays. OBJECTIVES: This study was designed to compare the dose-response of enoxaparin, dalteparin and unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT or aPTT can be used to monitor intravenous (IV) low molecular weight heparin (LMWH). METHODS: A total of 130 patients undergoing cardiac catheterization were assigned to intravenous enoxaparin 0.5 mg/kg, dalteparin 50 international units/kg or UFH 50 units/kg. Of the 130 patients, 46 (35%) underwent PCI, all of whom received a glycoprotein (GP) IIb/IIIa inhibitor. We measured ACT, activated partial thromboplastin time (aPTT) and plasma anti-Xa levels after serial sampling. RESULTS: Both enoxaparin and dalteparin induced a significant rise in the ACT and aPTT, with an ACT dose-response approximately one-half the magnitude of that obtained using UFH. The time course of changes in the ACT and aPTT after administration of enoxaparin and dalteparin was virtually identical, with a return to baseline at approximately 2 hours. The enoxaparin and dalteparin-treated patients successfully underwent PCI with no major hemorrhagic complications. CONCLUSIONS: The ACT is equally sensitive to IV enoxaparin and dalteparin. These data support an ACT-guided strategy for intravenously administered LMWH during PCI. Additional studies with larger patient populations may be indicated to determine the ideal target ACT for LMWH in PCI.     

Electrocardiographic determination of culprit lesion site in patients with acute coronary events

Purpose

The purpose of our study was to determine the ability of electrocardiographic (ECG) criteria derived from prior angiographic-ECG correlative studies to identify life-threatening coronary artery obstructive lesions.

Methods

We studied 128 consecutive patients referred from the emergency department for emergent coronary angiography for symptoms and ECG changes suggesting an acute coronary event. Using ECG criteria derived from prior studies, we attempted to predict not only the vessel housing the culprit lesion, but whether the lesion was located proximally in that vessel, and then determined the positive and negative predictive values (PPV and NPV) of the criteria used.

Results

Our criteria correctly identified 7 of 11 patients with left main disease, with a PPV of 100% and an NPV of 97%; 12 of 19 patients with proximal left anterior descending coronary artery disease, with a PPV of 67% and an NPV of 94%; and 25 of 28 patients with proximal right coronary artery disease, with a PPV of 64% and an NPV of 97%. The combined PPV and NPV for predicting patients with either left main coronary artery, proximal left anterior descending coronary artery, or proximal right coronary artery disease were 72% and 81%.

Conclusion

Our study indicates that the location of life-threatening coronary artery lesions in patients presenting with signs and symptoms of acute coronary syndromes can be predicted from the initial ECG with a high degree of accuracy. Recognizing the ECG criteria for such lesions has the potential for shortening door-to-reperfusion time and improving patient outcomes.     

Safety and efficacy of low-dose intravenous enoxaparin and GP IIb/IIIa inhibitor therapy during PCI

The use of intravenous enoxaparin, a glyco-protein (GP) IIb/IIIa inhibitor, during percutaneous coronary intervention (PCI) has been shown to be safe and to possibly reduce in-hospital and 30-day major adverse cardiac events(MACE). NICE-4, a recent PCI observational study, evaluated a reduced dose of intravenous (IV) enoxaparin (0.75 mg/kg) with abciximab. However, prior PCI studies evaluating IV enoxaparin have not used percutaneous closure devices. The purpose of this study was to observe the safety and efficacy of a lower dose of IV enoxaparin (0.5 mg/kg) in conjunction with any GP IIb/IIIa inhibitor. The Angio-Seal femoral closure device was also employed as part of the treatment strategy. We administered 0.5 mg/kg IV enoxaparin and a GP IIIb/IIIa inhibitor to 75 eligible PCI patients. None received anticoagulation 24 hours prior to PCI; all received pre-procedural aspirin, post-procedural deployment of the Angio-Seal and clopidogrel therapy, and were discharged home within 36 hours. TIMI minor bleeding was 1.3%; there were no TIMI major bleeding events or major adverse cardiac events during in-hospital stay or at 30-day follow-up. Our small observational study shows that IV enoxaparin is safe and efficacious during PCI when given at a dose 33% lower than previously reported in conjunction with any GP IIb/IIIa inhibitor and Angio-Seal. However, large, randomized PCI trials are needed to confirm the clinical efficacy, safety and cost-effectiveness of lower doses of enoxaparin with GPIIb/IIIa inhibitors and vascular closure devices.