[Show abstract][Hide abstract] ABSTRACT: Non-ST-segment elevation acute coronary syndromes (NSTE ACS) are highly prevalent in the United States and globally, and are associated with significant morbidity and mortality.
The key role of platelet-mediated thrombosis in the pathogenesis of NSTE ACS is confirmed by the proven clinical benefits of antiplatelet agents (aspirin and a P2Y(12) adenosine diphosphate [ADP] receptor antagonist) in this setting. Despite the documented advantages and broad use of antiplatelet therapy, the long-term morbidity and mortality rates remain significant, and the bleeding risk remains substantial. Residual risk can be attributed, at least in part, to the fact that thrombosis continues in the presence of current treatments because aspirin and P2Y(12) ADP receptor antagonists each block only one of multiple platelet activation pathways, and thus do not impact other platelet activation pathways, such as the one triggered by interaction of thrombin with protease-activated receptor (PAR)-1, thereby exposing patients to continued accumulation of thrombotic events.
These considerations suggest that novel therapies with a different mechanism of action, when used in combination with current antiplatelet agents, may provide more comprehensive inhibition of platelet activation and additional reductions in morbidity and mortality, potentially without incremental bleeding risk.
Preview · Article · Nov 2009 · Cardiovascular Drugs and Therapy
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to evaluate long-term mortality and identify factors associated with 1-year mortality in patients who underwent elective percutaneous coronary intervention (PCI).
While long-term outcomes in PCI patients have been reported previously, limited data are currently available regarding the comparative long-term outcomes in PCI patients who receive enoxaparin versus intravenous unfractionated heparin (UFH).
We conducted a follow-up analysis of clinical outcomes at 1 year in patients enrolled in the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation) trial of 3,528 patients undergoing elective PCI. Patients were randomized to receive either intravenous 0.50-mg/kg or 0.75-mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure.
Mortality rates were 1.4%, 2.0%, and 1.5% from 1 month to 1 year, and 2.3%, 2.2%, and 1.9% from randomization to 1 year, after index PCI in patients receiving 0.50 mg/kg enoxaparin, 0.75 mg/kg enoxaparin, and UFH, respectively. Multivariate analysis identified nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio: 3.5, 95% confidence interval: 1.7 to 7.3; p < 0.001), and major bleeding within 48 h (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.5; p = 0.04) as the strongest independent risk factors for 1-year mortality.
The 1-year mortality rates were low and comparable between patients receiving enoxaparin and UFH during elective PCI. Periprocedural ischemic or bleeding events were the strongest independent predictors of 1-year mortality. (The STEEPLE Trial; NCT00077844).
Full-text · Article · Nov 2009 · JACC. Cardiovascular Interventions
[Show abstract][Hide abstract] ABSTRACT: Achieving an appropriate balance of anti-ischemic efficacy versus bleeding risk with antiplatelet and anticoagulant agents demands an accurate estimation of risks. Although traditional risk stratification is available to decrease complications, and various methods of stratifying these risks have been proposed and validated, the stratification of bleeding risk is in its infancy. However, no model currently available permits the simultaneous estimation of these risks. Ischemic risk may be determined using 1 of several validated models, followed by the estimation of bleeding risk according to known risk factors. After selecting appropriate pharmacotherapy on the basis of the stratification of these risks, attention must be paid to proper dosing according to individual risk factors and patient, clinical, and technical variables. The aim of this study was to examine risk stratification models for these parameters to determine clinical characteristics common to ischemia and bleeding that can be used to minimize risks. A "bleeding risk subscale" is proposed, with factors extrapolated from current ischemic risk models, to integrate ischemic mortality and bleeding risk in patients with non-ST-segment elevation acute coronary syndromes. In conclusion, a validated tool to simultaneously evaluate ischemic and bleeding risk will help determine the most well-balanced pharmacotherapy for patients with non-ST-segment elevation acute coronary syndromes.
No preview · Article · Jun 2009 · The American journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic agents for the treatment of patients with acute coronary syndromes (ACS). In patients with unstable angina and non-ST segment elevation myocardial infarction (MI), many data support the use of the LMWH enoxaparin to reduce cardiovascular events and death. LMWHs also appear more effective than unfractionated heparin in reducing the composite end point of acute MI, recurrent ischemia, or death in patients with ST segment elevation MI, and can also be used effectively in patients undergoing thrombolysis reperfusion and percutaneous coronary intervention. However, the various LMWH preparations should not be used interchangeably. Each LMWH is a pleiotropic biological agent with a unique chemical, biochemical, biophysical, and biological profile, and it displays a unique pharmacodynamic and pharmacokinetic profile. As a result, LMWHs are not equipotent in preclinical assays or equivalent in terms of their clinical efficacy and safety. Therefore, it is essential that new, emerging, generic versions of LMWHs demonstrate clinical equivalence, in specific indications, with the existing approved LMWHs. This article highlights the chemical, biological, and pharmacological differences between the LMWH preparations that may result in different clinical outcomes during the treatment of patients with acute coronary syndromes.
No preview · Article · May 2009 · Journal of cardiovascular pharmacology
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is a risk factor for coronary heart disease and bleeding with antithrombotic therapy in patients with acute coronary syndromes (ACS). We evaluated the effect of renal function on efficacy and outcomes in high-risk patients with NSTE ACS in the SYNERGY trial.
Creatinine clearance (CrCl) at the time of randomization was analyzed as a continuous variable added to multivariable logistic regression models for 30-day death or MI, non-CABG-associated TIMI major bleeding, GUSTO severe bleeding, and transfusion in the overall study population, patients undergoing coronary angiography, and patients undergoing PCI.
Of 9838 patients with a CrCl value, 70.6% (N=6950) had CrCl≥60 mL/min, 27.8% (N=2732) had CrCl 30-59 mL/min, and 1.6% (N=156) had CrCl<30 mL/min. No randomized treatment by CrCl interaction test was found to be statistically significant, suggesting renal insufficiency affected enoxaparin and unfractionated heparin outcomes similarly. After adjustment, CrCl was an independent predictor of 30-day death or MI (OR 1.06, 95% CI 1.03-1.09), TIMI major bleeding (OR 1.06, 95% CI 1.02-1.10), GUSTO severe bleeding (OR 1.10, 95% CI 1.03-1.17), and transfusion (OR 1.07, 95% CI 1.04-1.11).
Patients with CKD had higher rates of 30-day death or MI and bleeding than those without CKD, regardless of randomized antithrombin therapy. While this analysis suggests that there is a rise in bleeding events as CrCl falls for patients in either treatment group, it is unknown whether a reduction in dose would decrease bleeding risk.
No preview · Article · Apr 2009 · International journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: Patent foramen ovale (PFO) is reported in up to 50% of patients with cryptogenic stroke. However, the role of PFO in acute myocardial infarction is less reported. In this case report, the relationship between PFO, myocardial infarction, and an interatrial paradoxical thromboembolism (aka thrombus-in-transit) was diagnosed with the use of non-invasive technique, percutaneous procedures, as well as gross surgical specimen.
No preview · Article · Apr 2009 · Journal of Thrombosis and Thrombolysis
[Show abstract][Hide abstract] ABSTRACT: Antiplatelet therapy is an evidence-based, guideline-recommended, worldwide standard of care for treatment of patients with atherothrombosis. However, clinical implementation of the guidelines is suboptimal, in part because of physician and patient nonadherence. The increased risk of bleeding associated with antiplatelet therapy is often the reason for nonadherence, and several programs have been created to increase adherence to guideline treatment recommendations. Despite the relative success of such initiatives, including Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines, Guidelines Applied in Practice, and the American Heart Association's Get With the Guidelines and a Science Advisory, a current estimate is that less than 50% of atherothrombotic patients are taking antiplatelet therapies as recommended by national guidelines. A PubMed and MEDLINE search of the literature (January 1, 1983-May 15, 2008) was performed to examine the bleeding risks associated with various antiplatelet therapies. Relevant clinical trials, observational registry data, and other studies relevant to treatment and guideline recommendations were selected from articles generated through specific search terms. This comprehensive review contributes to the understanding of the benefit-to-risk ratio of antiplatelet therapy for patients with atherothrombosis.
Preview · Article · Mar 2009 · Mayo Clinic Proceedings
[Show abstract][Hide abstract] ABSTRACT: Controversy regarding the optimal antiplatelet/antithrombotic regimen indicates a need to re-evaluate the place of these agents in treating patients with unstable angina/non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.
Although clinical trial data suggest that glycoprotein IIb-IIIa inhibition benefits moderate-risk to high-risk patients, recent studies question the use of intensive antiplatelet therapy in lower risk patients. The resultant shift towards less intensive alternative regimens raises questions about identifying patients in whom an alternative strategy is preferable. The concept of risk stratification for coronary intervention has evolved from lesion-based categorization to include clinical factors, for example, elevated levels of cardiac troponin.
Risk factors for periprocedural complications during percutaneous coronary intervention can be divided into anatomic (unprotected left main stenting, bifurcation lesions, and diffuse disease) and clinical (older age, diabetes, renal disease, left ventricular function, recent myocardial damage, and female sex) factors. These may interact additively or synergistically, increasing the likelihood of complications in patients who might otherwise have been considered at low risk. We need to reconsider, therefore, how we identify appropriate options and, hopefully, optimize clinical outcomes. This review evaluates risk factors for periprocedural complications in an effort to determine patients who may benefit most from intensive antiplatelet regimens.
No preview · Article · Feb 2009 · Current opinion in cardiology
[Show abstract][Hide abstract] ABSTRACT: To evaluate the occurrence, size and composition of embolized debris captured during routine directional atherectomy using the SilverHawk device.
15 consecutive eligible patients with a nonocclusive superficial femoral artery (SFA) were enrolled. Patients were included if they were > 18 years of age and had > or = 70% stenosis in the SFA. All lesions underwent plaque excision with the SilverHawk atherectomy device. A FilterWire EZ was used for distal protection and retrieval of embolized material. Specimens were collected separately from the filter basket and the SilverHawk atherectomy device's nosecone and were studied by a pathologist for number, size and composition.
Visible debris captured in the filter was found in the majority of patients 14/15 (93%). Clinically-significant debris was found in 7/15 (47%) patients. The proportion of captured debris ranged from 0.1-0.4 cm. Microscopy revealed that the shaved particles consisted predominantly of collagen, fibrin, lipid-laden macrophages, cholesterol and calcium. Analysis of the embolized material revealed a different composition, mostly consisting of collagen with fibrosis, cholesterol and macrophages.
In this single-center comparative study we have shown that during SilverHawk atherectomy of SFA lesions, distal embolization is universal. The debris captured in the filter is different in overall composition from the captured material in the nosecone of the SilverHawk device. Debris large enough to cause clinically-significant embolization, no-reflow and ischemia following SFA interventions occurred in nearly 50% of cases.
No preview · Article · Jan 2009 · The Journal of invasive cardiology
[Show abstract][Hide abstract] ABSTRACT: The STEEPLE trial assessed outcomes of patients undergoing elective percutaneous coronary intervention randomized to receive a bolus of intravenous enoxaparin (0.5 or 0.75 mg/kg, n = 2,298) or activated clotting time-adjusted unfractionated heparin (UFH, n = 1,230), stratified according to planned glycoprotein IIb/IIIa inhibitor use.
In this subanalysis, we assessed outcomes in patients with renal impairment (creatinine clearance < or =60 mL/min, n = 659).
Major bleeding occurred more often in patients with renal impairment compared with those without (2.7% vs 1.5%, P = .04). Enoxaparin was associated with less major bleeding than UFH with normal renal function (0.9% for enoxaparin 0.5 mg/kg or 1.0% for enoxaparin 0.75 mg/kg vs 2.6%, respectively; both P = .01 vs UFH), with a trend toward less major bleeding with impaired renal function (2.6% or 1.8% vs 3.8%, P = .18 for enoxaparin 0.5 mg/kg and P = .47 for 0.75 mg/kg vs UFH). Minor bleeding rates were similar irrespective of renal function or anticoagulation regimen. The incidence of death, nonfatal myocardial infarction, or urgent target-vessel revascularization was similar between patients with and without renal impairment (5.7% vs 6.5%, P = .45). In patients with renal impairment, event rates were 6.2% or 5.3% with enoxaparin vs 5.6% with UFH (P = nonsignificant). Target anticoagulation levels were achieved 4 to 5 times more often with enoxaparin compared with UFH in patients with normal and impaired renal function (both P < .0001).
A single bolus of enoxaparin was associated with similar ischemic events and a trend for less major bleeding compared with UFH in patients with renal impairment undergoing percutaneous coronary intervention. Enoxaparin can be administered safely without dose adjustment in these patients.
No preview · Article · Jan 2009 · American heart journal
[Show abstract][Hide abstract] ABSTRACT: Definitions of bleeding must be considered when evaluating results of clinical trials. Assessments of bleeding impact based on clinical criteria may be more relevant to patient outcomes than those based on simple laboratory measures like an isolated change in hemoglobin, that do not appear to affect patient care. The risk of excessive bleeding in patients who receive antiplatelet and antithrombotic therapy is related to a combination of patient characteristics (older age, female sex, impaired renal function), and delivery factors (excessive dosing, stacking of anticoagulants). Investigators should justify components of bleeding endpoints as being clinically meaningful, sufficiently frequent in the study population, and affected by the intervention.
No preview · Article · Dec 2008 · Journal of Thrombosis and Thrombolysis
[Show abstract][Hide abstract] ABSTRACT: Patients presenting to the Emergency Department (ED) need to be quickly diagnosed, risk-stratified, and treated accordingly. Anticoagulants used in the ED should be easy to use and suitable for all patients with acute coronary syndromes, regardless of treatment strategy. In patients with ST-segment myocardial infarction, current guidelines recommend unfractionated heparin regardless of reperfusion strategy or low-molecular-weight heparin (LMWH) as an alternative in patients undergoing percutaneous coronary intervention (PCI). The LMWH enoxaparin is approved for ST-segment elevation myocardial infarction patients managed medically or undergoing PCI. The recently updated American College of Cardiology/American Heart Association guidelines for patients with unstable angina or non-ST-segment elevation myocardial infarction recommend unfractionated heparin or the LMWH enoxaparin (class IA recommendation), or the factor Xa inhibitor fondaparinux or the direct thrombin inhibitor bivalirudin (class IB recommendation) for patients managed invasively. This review discusses each of these anticoagulant options in the context of patients transitioning to PCI.
No preview · Article · Nov 2008 · The American journal of emergency medicine
[Show abstract][Hide abstract] ABSTRACT: Enoxaparin use in PCI has been investigated, however its role in primary PCI is less known.
To evaluate the role of combination IV + SC enoxaparin in primary PCI in STEMI.
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).
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.
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.
No preview · Article · Oct 2008 · Journal of Thrombosis and Thrombolysis
[Show abstract][Hide abstract] ABSTRACT: With the availability of new data and the recent release of new European and US guidelines, contemporary care paradigms for the treatment of patients with non-ST-elevation acute coronary syndromes (NSTE ACS), including those undergoing percutaneous coronary intervention, are likely to undergo substantial changes. In recognition of this shifting landscape as well as the impact of new guidelines on care models for the treatment of patients with NSTE ACS, a roundtable was convened on October 25, 2007, to discuss the implications of these changes. The purpose of this review is to summarize the presentations and subsequent discussions from the roundtable, which examined the guidelines and evidence from a variety of perspectives, and to explore the best ways to incorporate new treatment paradigms into everyday clinical care. The multiple viewpoints expressed by the roundtable attendees illustrate the recognition that at this point, consensus has not been reached on the optimum algorithm for treatment of these patients. This article focuses on issues discussed during the roundtable from the perspective of the practicing cardiologist.
No preview · Article · Sep 2008 · Journal of Interventional Cardiology
[Show abstract][Hide abstract] ABSTRACT: Staphylococcus epidermidis is the most common organism associated with prosthetic valve endocarditis. Staphylococcus capitis, a coagulase-negative Staphylococcus, is a rare cause of endocarditis. We report two cases of S.capitis prosthetic valve endocarditis, both involving prosthetic aortic valve and complicated by aortic root abscess. We also review the literature for this rare condition caused by this rare organism.
No preview · Article · Sep 2008 · Heart & lung: the journal of critical care
[Show abstract][Hide abstract] ABSTRACT: Smoking remains a major public health issue. We investigated the incidence of smoking and outcomes in high-risk patients with acute coronary syndromes. Differences in treatment effect of antithrombin therapies were also investigated.
Using data from SYNERGY, patients were categorized by their self-reported smoking status. They were followed at 30 days and 6 months for death, nonfatal myocardial infarction (MI), revascularization procedures, stroke, and need for rehospitalization, and at 1 year for occurrences of death.
Overall, 9,971 patients were evaluated, of whom 2,404 (24%) were current smokers, 3,491 (35%) were former smokers, and 4076 (41%) had never smoked. Current smokers were younger (median age 61 years, interquartile range [IQR] 52-67) than former smokers (median age 69 years, IQR 63-75) and never smokers (median age 70 years, IQR 64-77) and had fewer additional coronary artery disease risk factors (hypertension, diabetes, hypercholesterolemia). The 30-day death/MI rate was similar for former versus never smokers (15% vs 13.6%, P = .079) and for current versus never smokers (14% vs 13.6%, P = .585). Adjusted odds ratios for 30-day death/MI in patients receiving enoxaparin compared with those receiving unfractionated heparin were 1.065 (95% CI 0.883-1.283, P = .51) in never smokers, 1.034 (95% CI 0.853-1.254, P = .733) in former smokers, and 0.742 (95% CI 0.582-0.948, P = .017) in current smokers. A significant interaction for treatment and smoking status was found at 30 days (P = .0215), but not at 6 months (P = .1381) or 1 year (P = .1054). One-year unadjusted mortality rates were higher for former versus never smokers (9.1% vs 6.7%, P = .0002) but were similar for current versus never smokers (6.5% vs 6.7%, P = .7226). On follow-up at 30 days, 62.3% (n =1397) of current smokers reported not smoking.
Smokers with non-ST-segment elevation acute coronary syndrome are generally younger and have fewer cardiac risk factors. A significant interaction of smoking and enoxaparin was seen at 30 days, but not sustained at 6 months and 1 year. More than 60% of smokers quit within 30 days of their cardiac event. There was little difference in outcomes from 30 days to 1 year for these smokers who quit versus those who did not.
No preview · Article · Aug 2008 · American heart journal
[Show abstract][Hide abstract] ABSTRACT: Early risk stratification of patients with acute coronary syndromes (ACS), unstable angina, or non-ST-elevation myocardial infarction ensures patients receive appropriate care.
Many risk-stratification models have been developed to identify high-risk ACS patients who would benefit most from an early invasive strategy and to determine patients at greater risk for bleeding complications. Although high-risk patients seem to benefit most from a combination of aggressive antithrombotic and early invasive therapies, stratification for risk of bleeding also helps in the choice and dosing of appropriate medical therapy.
The effective use of glycoprotein IIb/IIIa inhibitors, in particular, is dependent on accurate risk assessment, whereas the risk-to-benefit ratio of direct thrombin inhibitors in high-risk versus low-risk patients as part of an initial therapy plan requires clarification. Nevertheless, use of the same anticoagulant throughout the care pathway may reduce the rates of death or recurrent myocardial infarction, and bleeding complications.
No preview · Article · Aug 2008 · Cardiovascular Drugs and Therapy