Cardiac troponins in suspected acute coronary syndrome: a meta-analysis of published trials.

We performed a meta-analysis of published trials to determine the predictive value of cardiac troponin I (cTnI) and T (cTnT) levels for adverse events (death and myocardial infarction) in acute coronary syndrome without ST elevation (ACS). The accumulated odds ratio (OR) for adverse events (30 days) in ACS with elevated cTnI (n = 5,759) and cTnT (n = 5,483) was 4.9 (95% confidence interval, CI, 3.9-6.2) and 4.6 (95% CI 3.8-5.5), respectively. Trials that mandated timed serum sampling (6 or more hours after symptom onset) had an improved predictive value for elevated cTnI (n = 2,807, OR 8.8; 95% CI 5.9-13.2) and cTnT (n = 1,990, OR 8.5; 95% CI 5.9-12.5). In conclusion, cTnI and cTnT provide similar information in ACS. The risk of adverse events is 4-fold higher in patients with suspected ACS and elevated serum cTn. For patients with an elevated timed (6-hour) sample the risk is over 8-fold higher.     

Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events.

AIMS: To determine whether low-molecular-weight heparin (LMWH)+glycoprotein (GP) IIb/IIIa inhibitors provide greater benefit than unfractionated heparin (UFH)+GP IIb/IIIa inhibitors, irrespective of renal status. METHODS AND RESULTS: Patients in the Global Registry of Acute Coronary Events (GRACE) were divided into three groups according to creatinine clearance (CrCl): normal renal function (CrCl >60 mL/min), moderate renal dysfunction (30相似文献   

Incidence of high-risk acute coronary syndromes and eligibility for glycoprotein IIb/IIIa inhibitors among patients admitted for possible myocardial ischemia

Objective Recent studies have demonstrated that glycoprotein (GP) IIb/IIIa inhibitors can reduce cardiac events in patients with acute coronary syndromes (ACS). However, little is known about how many patients are actually eligible for treatment. Our purpose was to determine how many patients admitted for possible myocardial infarction (MI) meet GP IIb/IIIa inhibitor treatment criteria. Methods Patients admitted for possible MI who underwent a standard protocol that included serial sampling of total creatine kinase (CK), CK-MB, and troponin I (TnI) were retrospectively assigned to different treatment algorithms on the basis of criteria from GP IIb/IIIa inhibitor trials: an electrocardiogram (ECG) consistent with acute MI or ischemia, and myocardial marker elevations. Elevated CK-MB was considered diagnostic of MI. High-risk ACS was defined as ischemic ECG changes or troponin elevations without CK-MB elevations. Results A total of 2179 patients were admitted for MI exclusion. MI was identified in 304 patients (14.0%) (123 ST-elevation, 49 ischemic ECG, 132 nonischemic ECG). Another 273 patients (12.5%) without CK-MB criteria for MI met high-risk ACS criteria (172 ischemic ECG, 120 TnI elevations). Ischemic ECGs or elevated myocardial markers identified 454 (21%) patients as eligible for treatment. Inclusion of patients with ST elevation increased eligibility to 26.5%. Of the 454 non-ST-elevation ACS patients, 340 (74%) were identified early by the ECG or the initial markers. Conclusions A large proportion of patients admitted for possible MI met criteria for treatment with GP IIb/IIIa inhibitors. The non-ST-elevation ACS group was >3 times larger than the ST-elevation MI group. These findings have important implications for treatment of patients with ACS. (Am Heart J 2002;143:70-5.)     

Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study

Background

In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI).

Methods

The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia.

Results

A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively).

Conclusions

The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.     

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.     

Platelet function in clopidogrel-treated patients with acute coronary syndrome.

Percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS) is associated with increased risk of thrombotic complications. ACS enhances platelet activation; whether pretreatment with clopidogrel is sufficient to suppress platelet function in patients with ACS is not known. This study assessed platelet function in patients with and without ACS prior to PCI and after pretreatment with a single dose of 600 mg clopidogrel. Blood samples of 402 patients prior to PCI with (n = 119) or without (n = 283) ACS were collected at least 2 h after 600 mg clopidogrel administration. Maximal platelet aggregation in response to ADP (5 and 20 micromol/l), collagen (4 microg/ml) and TRAP (25 micromol/l) was measured with optical aggregometry. Surface expression of glycoprotein IIb/IIIa and P-selectin was assessed with flow cytometry at baseline and after stimulation with 5 and 20 micromol/l ADP. Agonist-induced platelet aggregation did not differ significantly between patients with and without ACS (P > or = 0.15). Parameters of platelet activation (glycoprotein IIb/IIIa and P-selectin surface expression) were significantly higher in ACS patients at baseline and after 5 and 20 micromol/l ADP stimulation (P < 0.0001). Patients with ACS continue to exhibit increased platelet activation after pretreatment with 600 mg clopidogrel. This finding supports the need for additional platelet function inhibition during PCI in patients with ACS.     

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.     

Safety and effectiveness of combined low molecular weight heparin and glycoprotein IIb/IIIa inhibitors

This study examines the safety and efficacy of low molecular weight heparin (LMWH) in combination with platelet glycoprotein (GP) IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI). LMWH has been shown to be as effective as unfractionated heparin (UFH) in the treatment of acute coronary syndrome (ACS), but there are limited data regarding the safety and efficacy of LMWH in combination with GP IIb/IIIa inhibitors. We studied 37,320 patients in the National Registry of Myocardial Infarction 3 who were treated with GP IIb/IIIa receptor antagonists from April 1998 to September 2000. Using univariate analysis, clinical events were compared between 2,482 patients who received LMWH and 34,838 patients who were treated with UFH. To adjust for confounding covariates, a multivariate regression analysis was also performed. Major bleeding rates were 4.0% in patients on LMWH versus 4.2% in patients who were treated with UFH (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.80 to 1.23, p = 0.92). Similarly, there was no significant difference in the occurrence of recurrent myocardial ischemia (OR 0.93, 95% CI 0.82 to 1.06, p = 0.26), and in-hospital death (OR 0.86, 95% CI 0.71 to 1.05, p = 0.14) between groups. There was a trend toward a decreased risk of recurrent AMI in patients who received LMWH compared with those on UFH (1.5% vs 1.9%, OR 0.74, 95% CI 0.53 to 1.05, p = 0.09). LMWH appears to be a safe and effective alternative to UFH in patients with AMI who receive IIb/IIIa inhibitors.     

Clinical significance of cardiac troponins I and T in acute heart failure

BACKGROUND: Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF). AIMS: To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF. METHODS: FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed. RESULTS: Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2-3.5, p=0.01) and cTnT (OR 2.6, 95% CI 1.5-4.4, p=0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2-13, p<0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0-1.8, p=0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8-0.9, p=0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality. CONCLUSIONS: cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.     

Ischemia Modified Albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T

BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients. METHODS: We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs.     

Clinical trial--derived risk model may not generalize to real-world patients with acute coronary syndrome

Background

Accurate risk stratification can guide clinical decision-making in the management of acute coronary syndromes (ACS). However, the applicability of risk models to the general ACS population remains unclear. The purpose of this study was to validate and compare a modified international clinical trial and a registry-based risk model in a contemporary, less selected ACS population.

Methods

In the prospective, observational Canadian ACS Registry, 4627 patients with ACS were enrolled from 51 centers. Baseline patient data were recorded on standardized case report forms. We evaluated risk models derived from the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) and the Global Registry of Acute Cardiac Events (GRACE) predicting in-hospital death among patients with non-ST-elevation ACS. Model discrimination was measured by the c-statistic, and calibration was assessed graphically and by the Hosmer-Lemeshow goodness-of-fit test.

Results

In-hospital mortality rates were 2.4% overall and 1.5% among the patients with non-ST-elevation ACS (n = 2925; 63.2%) in our validation cohort. Both the in-hospital PURSUIT and GRACE risk models showed similar and good prognostic discrimination (c-statistics = 0.84 and 0.83, respectively; P = .69 for difference). The GRACE model also demonstrated good calibration (Hosmer-Lemeshow P = .40). In contrast, calibration in the PURSUIT model was poor (Hosmer-Lemeshow P < .001), with consistent overestimation of risks.

Conclusions

Both the PURSUIT and GRACE models demonstrated good discrimination for in-hospital mortality rates in the Canadian ACS Registry. However, the GRACE risk model, derived from a less selected population, provided superior calibration in risk assessment across the spectrum of ACS. Our findings underscore the potential importance of risk model validation in the general ACS population rather than a clinical trial population to establish its generalizability before integration into clinical practice.     

Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors

OBJECTIVES: The purpose of this study was to examine the in-hospital outcome and influence of glycoprotein (GP) IIb/IIIa antagonists on patients with acute coronary syndromes (ACS) across a range of renal function. BACKGROUND: Recent studies demonstrate increasing cardiovascular risk with progressive renal dysfunction. Previous studies investigating GP IIb/IIIa antagonist use have excluded patients with renal dysfunction. METHODS: Patients presenting with ACS between January 1999 and May 2000 were identified, and data on demographics, in-hospital management, and clinical events were collected using standardized definitions. Patients were stratified according to renal function assessed by calculated creatinine clearance (CrCl) at presentation. Primary outcome measures included in-hospital mortality and major bleeding events. RESULTS: Renal insufficiency was present in 312 of 889 patients. There were 40 in-hospital deaths. In non-dialysis-dependent patients, as CrCl worsened, there was a decline in utilization of routine diagnostics and therapeutics, an increase in in-hospital mortality (p = 0.002), and an increase in major bleeding (p = 0.03). Although the use of GP IIb/IIIa antagonists was associated with an increase in major bleeding (p < 0.001), there was a protective effect on in-hospital mortality (p = 0.04) after controlling for CrCl. CONCLUSIONS: Renal dysfunction is present in a substantial proportion of patients with ACS and is associated with increased in-hospital death. Although GP IIb/IIIa antagonist use in patients with ACS and renal insufficiency resulted in increased bleeding events, its administration was associated with a decreased risk of in-hospital mortality. These preliminary findings need to be confirmed in future randomized clinical trials.     

The role of risk stratification in the decision to provide upstream versus selective glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: a cost-effectiveness analysis.

OBJECTIVES: We endeavored to determine under what conditions a strategy of upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for all acute coronary syndromes (ACS) patients is cost effective compared to that of selective use of abciximab in only those patients requiring percutaneous coronary intervention (PCI). BACKGROUND: Small molecule GP IIb/IIIa inhibitors have shown benefit in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be more effective during PCI. However, abciximab does not have proven efficacy in medical management. No prior study has attempted to balance these competing benefits. METHODS: A decision analysis was performed to examine two strategies: 1) treat all ACS patients upstream with a small molecule GP IIb/IIIa inhibitor and continue through medical management and PCI, if performed; or 2) wait, and selectively use abciximab only in patients who ultimately undergo PCI. Applicable randomized controlled trial data were used for the principal analysis. RESULTS: The strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was superior to selective use, and economically acceptable, with a cost-effectiveness ratio of 18,000 dollars per year of life gained. The superiority of the upstream use strategy persisted over the majority of sensitivity analyses. When stratified by risk according to Thrombolysis in Myocardial Infarction risk score, a strategy of upstream use was only cost effective in those patients with moderate or high risk. CONCLUSIONS: Upstream use of small molecule GP IIb/IIIa inhibition in ACS patients with moderate or high risk for cardiovascular events is a cost-effective approach that should be considered in this subset of patients.     

Early angioplasty in acute coronary syndromes without persistent ST-segment elevation improves outcome but increases the need for six-month repeat revascularization: an analysis of the PURSUIT Trial. Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy

OBJECTIVES: We explored the effect of timing of percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS) without persistent ST-segment elevation on the need for repeat revascularization, and we related this effect to other events. BACKGROUND: Percutaneous coronary intervention is widely used to treat ACS without persistent ST-segment elevation. Moreover, restenosis and subsequent revascularization after PCI are more frequent in ACS than in stable angina. The optimal timing of PCI in ACS without persistent ST-segment elevation is unknown. METHODS: In the Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) database, patients were stratified by the time of PCI. In the PURSUIT trial, 9,461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide or placebo for 72 h. The investigators decided on other treatments. RESULTS: A total of 2,430 patients underwent PCI within 30 days. Repeat revascularization (during 165 days) was notably higher for PCI within 24 h of enrollment (n = 620 [19%]) than for PCI at 24 to 72 h (n = 624 [16.7%]), 3 to 7 days (n = 614 [13.2%]), or 8 to 30 days (n = 561 [7.7%]; p < 0.001), regardless of eptifibatide use. This gradual reduction in the revascularization rate for later PCI was also observed after multivariate analysis correcting for baseline characteristics and with time as a continuous variable. CONCLUSIONS: Percutaneous coronary intervention within 24 is associated with improved outcome (other analysis) but more repeat revascularization. Prospective analyses are needed to test the hypothesis that rapid PCI in ACS with a platelet glycoprotein IIb/IIIa receptor antagonist reduces myocardial infarction (and possibly death) and is therefore most suited for patients at highest risk of infarction, despite a higher need for repeat revascularization.     

Admission risk assessment by cardiac troponin T in unstable coronary artery disease: additional prognostic information from continuous ST segment monitoring. TRIM study group. Thrombin Inhibition in Myocardial Ischemia.

OBJECTIVES: We investigated whether the addition of 24 h of continuous vectorcardiography ST segment monitoring (cVST) for an early (within 24 h of the latest episode of angina) determination of cardiac troponin T (cTnT) could provide additional prognostic information in patients with unstable coronary artery disease (UCAD), i.e., unstable angina and non-Q wave myocardial infarction. BACKGROUND: Determination of cTnT at admission and cVST are individually reported to be valuable techniques for the risk assessment of patients with UCAD. METHODS: Two hundred and thirty-two patients suspected of UCAD were studied. Patients were followed for 30 days, and the occurrence of cardiac death or acute myocardial infarction (AMI) were registered. RESULTS: One ST segment episode or more (relative risk [RR] 7.43, p = 0.012), a cTnT level > or = 0.20 microg/liter (RR 3.85, p = 0.036) or prestudy medication with calcium antagonists (RR 3.31, p = 0.041) were found to carry independent prognostic information after multivariate analysis of potential risk variables. By combining a cTnT determination and subsequent cVST for 24 h, subgroups of patients at high (25.8%) (n = 31), intermediate (3.1%) (n = 65) and low risk (1.7%) (n = 117) of death or AMI could be identified. CONCLUSIONS: Twenty-four hours of cVST provides additional prognostic information to that of an early cTnT determination in patients suspected of having UCAD. The combination of biochemical and electrocardiographic methods provides powerful and accurate risk stratification in UCAD.     

Complementary prognostic values of ST segment deviation and Thrombolysis In Myocardial Infarction (TIMI) risk score in non-ST elevation acute coronary syndromes: Insights from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study

BACKGROUND:

Although the Thrombolysis In Myocardial Infarction (TIMI) score incorporates ST deviation, it does not account for characteristics of the ST deviations. In the present study, it was hypothesized that the magnitude and characteristics of ST deviation may add to the prognostic values of the TIMI risk score in acute coronary syndrome (ACS) patients, particularly in lower-risk patients with a TIMI risk score of less than 5.

OBJECTIVE:

To evaluate the prognostic value of combining the TIMI risk score and characteristics of ST deviation in patients with non-ST elevation ACS and a TIMI risk score of less than 5.

METHODS:

The death/myocardial infarction (MI) rates of 1296 patients enrolled in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) angiographic substudy were examined.

RESULTS:

Patients without a TIMI risk score of 5 or greater, and without an ST deviation of 1 mm or greater had the lowest six-month rate of death/MI (5%). In patients with a TIMI risk score of less than 5, the six-month death/MI rate was increased in those with ST depression of 2 mm or greater compared with patients with a similar TIMI risk score and without ST deviation of 1 mm or greater (24% versus 5%, P<0.001). The presence of ST deviation of 2 mm or greater identified an additional 15% of patients with an increased six-month death/MI rate in patients with a TIMI risk score of less than 5.

CONCLUSION:

ST segment deviation of 2 mm or greater confers additional prognostic information in non-ST elevation ACS patients with a TIMI risk score of less than 5. Patients with a TIMI risk score of less than 5 and ST deviation of 2 mm or less had the lowest risk of six-month death/MI.     

Cardiac troponin T in chest pain unit patients without ischemic electrocardiographic changes: angiographic correlates and long-term clinical outcomes

OBJECTIVES

We prospectively evaluated the relation between cardiac troponin T (cTnT) level, the presence and severity of coronary artery disease (CAD) and long-term prognosis in patients with chest pain but no ischemic electrocardiographic (ECG) changes who had short-term observation.

BACKGROUND

Cardiac TnT is a powerful predictor of future myocardial infarction (MI) and death in patients with ECG evidence of an acute coronary syndrome. However, for patients with chest pain with normal ECGs, it has not been determined whether cTnT elevation is predictive of CAD and a poor long-term prognosis.

METHODS

In 414 consecutive patients with no ischemic ECG changes who were triaged to a chest pain unit, cTnT and creatine kinase, MB fraction (CK-MB) were evaluated ≥10 h after symptom onset. Patients with adverse cardiac events, including death, MI, unstable angina and heart failure were followed for as long as one year.

RESULTS

A positive (>0.1 ng/ml) cTnT test was detected in 37 patients (8.9%). Coronary artery disease was found in 90% of 30 cTnT-positive patients versus 23% of 144 cTnT-negative patients who underwent angiography (p < 0.001), with multivessel disease in 63% versus 13% (p < 0.001). The cTnT-positive patients had a significantly (p < 0.05) higher percent diameter stenosis and a greater frequency of calcified, complex and occlusive lesions. Follow-up was available in 405 patients (98%). By one year, 59 patients (14.6%) had adverse cardiac events. The cumulative adverse event rate was 32.4% in cTnT-positive patients versus 12.8% in cTnT-negative patients (p = 0.001). After adjustment for baseline clinical characteristics, positive cTnT was a stronger predictor of events (chi-square = 23.56, p = 0.0003) than positive CK-MB (>5 ng/ml) (chi-square = 21.08, p = 0.0008). In a model including both biochemical markers, CK-MB added no predictive information as compared with cTnT alone (chi-square = 23.57, p = 0.0006).

CONCLUSIONS

In a group of patients with chest pain anticipated to have a low prevalence of CAD and a good prognosis, cTnT identifies a subgroup with a high prevalence of extensive and complex CAD and increased risk for long-term adverse outcomes.     

Antiplatelet Strategies: Evaluating Their Current Role in the Setting of Acute Coronary Syndromes

Numerous clinical trials have established the value of antiplatelet therapies for acute coronary syndromes (ACS). Aspirin (ASA), thienopyridines (i.e., clopidogrel and ticlopidine) and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS and for the prevention of thrombotic complications of percutaneous coronary intervention (PCI). Clopidogrel is beneficial when administered before and after PCI, and is more effective when combined with either ASA or GP IIb/IIIa inhibitors in preventing post‐PCI complications, coronary subacute stent thrombosis, and thrombotic events in general. It is currently unclear whether a higher loading dose of clopidogrel (600 mg) is better than the standard loading dose (300 mg), how long therapy should continue, and which maintenance dose is optimal. The role of the GP IIb/IIIa antagonists in ACS is less clear due to conflicting data from several studies with different patient populations. Currently, it appears that the use of GP IIb/IIIa antagonists might be most beneficial in high‐risk ACS patients scheduled to undergo PCI, who demonstrate non‐ST‐segment elevation myocardial infarction and elevated troponin levels. Copyright © 2008 Wiley Periodicals, Inc.     

Low-molecular-weight heparin compared with unfractionated heparin for patients with non–ST-segment elevation acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors: Results from the CRUSADE initiative

Background: Both heparin and glycoprotein (GP) IIb/IIIa inhibitor therapy and early invasive management strategies are recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the treatment of patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). However, controversy exists about which form of heparin—unfractionated (UF) or low-molecular-weight (LMW)—is preferable. We sought to compare the efficacy and safety of these treatment strategies in a large contemporary population of patients with NSTE ACS. Methods: Using data from the CRUSADE Initiative, we evaluated LMWH and UFH in high-risk NSTE ACS patients (positive cardiac markers and/or ischemic ST-segment changes) who had received early (< 24 hours) GP IIb/IIIa inhibitor therapy and underwent early invasive management. In-hospital outcomes were compared among treatment groups. Results: From a total of 11,358 patients treated at 407 hospitals in the US from January 2002–June 2003, 6881 (60.6%) received UFH and 4477 (39.4%) received LMWH. Patients treated with UFH were more often admitted to a cardiology inpatient service (73.6% vs. 65.5%, P < 0.0001) and more frequently underwent diagnostic catheterization (91.8% vs. 85.9%, P < 0.0001) and percutaneous coronary intervention (PCI) (69.7% vs. 56.9%, P < 0.0001) than patients treated with LMWH. The point estimate of the adjusted risk of in-hospital death or reinfarction was slightly lower among patients treated with LMWH (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.67–0.99) and the risk of red blood cell transfusion was similar (OR 1.01, 95% CI 0.89–1.15). Among patients who underwent PCI within 48 hours, adjusted rates of death (OR 1.14, 95% CI 0.71–1.85), death or reinfarction (OR 0.93, 0.67–1.31), and transfusion (OR 1.16, 0.89–1.50) were similar. Patients who underwent PCI more than 48 hours into hospitalization had reduced rates of death (OR 0.64, 0.46–0.88), death or reinfarction (OR 0.57, 0.44–0.73), and transfusion (OR 0.66, 0.52–0.84). Conclusions: In routine clinical practice, patients treated with GP IIb/IIIa inhibitors have slightly improved outcomes and similar bleeding risks with LMWH than with UFH. These findings are consistent with current ACC/AHA guidelines but raise important questions about the safety and effectiveness of antithrombotic therapy in real-world clinical practice. Abbreviations abstract Using data from the CRUSADE Initiative, we evaluated low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in high-risk patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS) who received early (<24 hours) glycoprotein (GP) IIb/IIIa inhibitors and early invasive management. In-hospital outcomes were compared among treatment groups. LMWH was associated with slightly improved clinical outcomes and similar rates of transfusion compared with UFH. Our results support the current ACC/AHA guidelines recommendations but raise concerns about the safety and efficacy of UFH in the setting of background use of upstream GP IIb/IIIa inhibitors for patients with NSTE ACS in routine clinical practice. CRUSADE is funded by Millennium Pharmaceuticals, Inc. (Cambridge, Massachusetts) and Schering Corporation (Kenilworth, New Jersey). Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership provides an unrestricted grant in support of the program.     

Underuse of evidence-based treatment modalities in diabetic patients with non-ST elevation acute coronary syndrome. A prospective nation wide study on acute coronary syndrome (FINACS)

This study was designed to evaluate how new treatment guidelines of acute coronary syndrome (ACS) without ST elevation have been implemented in clinical practice especially in diabetic patients. A prospective follow-up was performed on 501 consecutive patients with suspected ACS without ST elevation admitted to nine hospitals in Finland between 15 January and 11 March 2001. The study group included 143 (29%) diabetic patients. Their risk profile was more severe than in non-diabetic patients; ST-depression on admission electrocardiography 57 versus 38%; P<0.0001, elevated troponin levels 66 versus 56%; P<0.05. Six months composite incidence of death, new myocardial infarction (MI), refractory angina or readmission for unstable angina was 39% in diabetic patients and 20% in non-diabetic patients (P<0.0001). In spite of this more severe risk profile, glycoprotein (GP) IIb/IIIa receptor antagonists and statins were used with similar frequency in non-diabetic and diabetic patients (15 vs. 19 and 48 vs. 54%, respectively; P=NS for both). In diabetic patients mean delay for in hospital coronary angiography was longer (6.4 vs. 4.2 days, P<0.05) and it was performed less often (32 vs. 45% P<0.05). Our results show that diabetic patients with ACS have higher risk profile and worse outcome than non-diabetic patients. Despite their indisputable benefits in diabetic patients, statins, GP IIb/IIIa receptor antagonists and invasive strategy were underused or often neglected. Further education is needed to change attitudes and to better implement new guidelines into clinical practice.