Elevated creatine kinase-MB with normal creatine kinase predicts worse outcomes in patients with acute coronary syndromes: results from 4 large clinical trials.

BACKGROUND: The degree to which elevated creatine kinase (CK)-MB in the presence of normal CK is predictive of outcome is not well understood despite having been studied for decades. This analysis examined whether normal CK with elevated CK-MB in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) is an independent predictor of worse outcomes. A concomitant goal was to contribute insight to the debate over how patients with NSTE ACS should be managed. METHODS: Data for 25,960 patients from the GUSTO IIb, PARAGON A and B, and PURSUIT trials were analyzed. Of these patients, 6402 were excluded from primary analysis because of missing (unmeasured) biomarkers. Patients with complete laboratory data (n = 19,558) were grouped by CK and CK-MB results. To confirm the primary analysis results, data from patients with missing biomarkers were used in an imputation model. RESULTS: Patients were categorized in 1 of 4 groups: normal CK + normal CK-MB; normal CK + elevated CK-MB; elevated CK + normal CK-MB; or elevated CK + elevated CK-MB. For the primary outcome, 180-day death, or myocardial infarction, Kaplan-Meier estimates were 14.9%, 20.8%, 14.5%, and 18.2%, respectively. Regardless of total CK, elevated CK-MB was associated with a 25% to 49% increased relative risk of worse outcomes. Findings from the analyses were verified by the multivariable model. CONCLUSIONS: CK-MB remains a reliable marker for myocardial necrosis and a strong predictor of worse prognosis. All patients with ACS should have CK-MB measurement to search for cardiac ischemia. Patients with elevated CK-MB should receive aggressive management commensurate with their increased risks.

Triple antiplatelet therapy during percutaneous coronary intervention is associated with improved outcomes including one-year survival: results from the Do Tirofiban and ReoProGive Similar Efficacy Outcome Trial (TARGET).

OBJECTIVE: We sought to examine if clopidogrel treatment initiated before coronary stenting improved clinical outcomes among patients receiving aspirin and a glycoprotein (GP) IIb/IIIa inhibitor. BACKGROUND: Antiplatelet therapy plays a pivotal role in contemporary percutaneous coronary interventions (PCI). METHODS: Outcomes among 4,809 patients randomized to tirofiban or abciximab during PCI with stent placement were compared according to whether they received 300 mg of clopidogrel before PCI (93.1%) versus immediately after the procedure. RESULTS: The 30-day primary composite end point (death, myocardial infarction [MI], or urgent target vessel revascularization [TVR]) was lower among clopidogrel-pretreated patients (6.6% vs. 10.4%, p = 0.009), mainly because of reduction of MI (6.0% vs. 9.5%, p = 0.012). The benefit of clopidogrel pretreatment was sustained at six months (death, MI, any TVR: 14.6% vs. 19.8%, HR = 0.71, p = 0.010), and this was due mainly to lowering of death and MI (7.8% vs. 13.0%, p = 0.001). At one year, clopidogrel pretreatment was associated with a lower mortality rate (1.7% vs. 3.6%, p = 0.011). Because clopidogrel pretreatment was not randomized, multivariable and propensity analyses were performed. After adjusting for baseline heterogeneity, clopidogrel pretreatment was an independent predictor for death or MI at 30 days (HR = 0.63, p = 0.012) and at six months (HR = 0.61, p = 0.003), and survival at one year (HR = 0.53, p = 0.044). No excess in 30-day bleeding events was noted with clopidogrel pretreatment. CONCLUSIONS: Among patients undergoing coronary stent placement with aspirin and a GP IIb/IIIa inhibitor, clopidogrel pretreatment is associated with a reduction of death and MI irrespective of the type of GP IIb/IIIa inhibitor used.

Prevalence of conventional risk factors in patients with coronary heart disease.

CONTEXT: It is commonly suggested that more than 50% of patients with coronary heart disease (CHD) lack any of the conventional risk factors (cigarette smoking, diabetes, hyperlipidemia, and hypertension). This claim implies that other factors play a significant role in CHD and has led to considerable interest in nontraditional risk factors and genetic causes of CHD. OBJECTIVE: To determine the prevalence of the 4 conventional risk factors among patients with CHD. DESIGN, SETTING, AND PATIENTS: In 2002-2003, we analyzed data for 122458 patients enrolled in 14 international randomized clinical trials of CHD conducted during the prior decade. Patients included 76716 with ST-elevation myocardial infarction, 35527 with unstable angina/non-ST-elevation myocardial infarction, and 10215 undergoing percutaneous coronary intervention. MAIN OUTCOME MEASURES: Prevalence of each conventional risk factor and number of conventional risk factors present among patients with CHD, compared between men and women and by age at trial entry. RESULTS: Among patients with CHD, at least 1 of the 4 conventional risk factors was present in 84.6% of women and 80.6% of men. In younger patients (men < or =55 years and women < or =65 years) and most patients presenting either with unstable angina or for percutaneous coronary intervention, only 10% to 15% of patients lacked any of the 4 conventional risk factors. This pattern was largely independent of sex, geographic region, trial entry criteria, or prior CHD. Premature CHD was related to cigarette smoking in men and cigarette smoking and diabetes in women. Smoking decreased the age at the time of CHD event (at trial entry) by nearly 1 decade in all risk factor combinations. CONCLUSIONS: In direct contrast with conventional thinking, 80% to 90% of patients with CHD have conventional risk factors. Although research on nontraditional risk factors and genetic causes of heart disease is important, clinical medicine, public health policies, and research efforts should place significant emphasis on the 4 conventional risk factors and the lifestyle behaviors causing them to reduce the epidemic of CHD.

Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials.

INTRODUCTION: Oxidised LDL is thought to play an important part in the pathogenesis of atherosclerosis. Observational studies have associated alpha tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular events, but not clinical trials. We did a meta-analysis to assess the effect of these compounds on long-term cardiovascular mortality and morbidity. METHODS: We analysed seven randomised trials of vitamin E treatment and, separately, eight of beta carotene treatment; all trials included 1000 or more patients. The dose range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up ranged from 1.4 to 12.0 years. FINDINGS: The vitamin E trials involved a total of 81788 patients and the beta carotene trials 138113 in the all-cause mortality analyses. Vitamin E did not provide benefit in mortality compared with control treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11] p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1 [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis. INTERPRETATION: The lack of a salutary effect was seen consistently for various doses of vitamins in diverse populations. Our results, combined with the lack of mechanistic data for efficacy of vitamin E, do not support the routine use of vitamin E.

Variability of area measurements obtained with different intravascular ultrasound catheter systems: Impact on clinical trials and a method for accurate calibration.

BACKGROUND: Atherosclerotic plaque burden is the major end point in ongoing progression trials. Intravascular ultrasound allows precise measurements of coronary artery dimensions. However, the variability of measurements among different catheter systems is incompletely characterized. METHODS: Intravascular ultrasound imaging was performed in a cylindric phantom with 5 sections of different, known, cross-sectional area ranging from 3.24 to 27.99 mm(2). A total of 3637 measurements with different catheter systems (Atlantis SR and Ultracross, Scimed/Boston Scientific; and Invision and Avanar, Jomed) were performed. Measurements were divided into model building and validation datasets. For each catheter, calibration models were developed. RESULTS: Overestimation and underestimation of the true cross-sectional area of up to 18% was observed with different catheter systems. Calibration equations for the different systems could be developed that predicted the true diameter and area with high statistical precision (adjusted R(2) > 0.99). CONCLUSIONS: Area measurements vary among different intravascular ultrasound catheter systems. Calibration equations can correct for these differences and allow the comparison of measurements among catheters.

Reduction in vascular access site bleeding in sequential abciximab coronary intervention trials.

We analyzed vascular access site bleeding from the EPIC, EPILOG, and EPISTENT trials to quantify the decrease in vascular bleeding complications in these three trials, especially those attributable to abciximab. The incidence of combined major and minor vascular access site bleeding in nonabciximab (heparin plus placebo) patients progressively decreased from EPIC (8.2%) to EPILOG (2.9%) to EPISTENT (1.7%; P < 0.001). Combined major and minor vascular access site bleeding in abciximab (heparin plus abciximab) patients decreased from EPIC (20%) to EPILOG (5.8%) to EPISTENT (2.2%; P < 0.001). There were more major vascular access site bleeds with abciximab compared to placebo in EPIC (odds ration 3.2; P < 0.001) but not in EPILOG or EPISTENT. Modified abciximab and heparin dosing and improved vascular access site management strategies have decreased the risk of vascular access bleeding during coronary intervention and have essentially eliminated the excess access site bleeding associated with abciximab.

Assessing the effect of publication of clinical guidelines on the management of unstable angina and non-ST elevation myocardial infarction in the TIMI III (1990-1993) and the GUARANTEE (1995-1996) Registries.

BACKGROUND: The clinical guidelines for unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) published in 1994 by the Agency for Health Care Policy Research (AHCPR) were intended to help improve treatment. No large study, however, has evaluated the effect of the guidelines on clinical practice METHODS: We compared the treatment of 3,318 patients admitted with UA/NSTEMI in the preguideline Thrombolysis in Myocardial Infarction (TIMI) III Registry (1990-1993) and 2,948 patients enrolled in the postguideline Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry (1995-1996). RESULTS: More patients in GUARANTEE received guideline-recommended medication than did those in TIMI III, specifically beta-blockers (50.9% vs. 40.7%, P < 0.001), heparin (63.3% versus 57.5%, P < 0.001), and the combination of aspirin, heparin, and beta-blockers on admission plus aspirin at discharge (26.9% vs. 18.8%, P < 0.001). These changes were similar in all subgroups, but the greatest improvement in medication use was seen in patients admitted to a tertiary care hospital and in those with a final diagnosis of NSTEMI, i.e., with positive cardiac markers. Conversely, fewer patients in GUARANTEE who fulfilled AHCPR criteria for catheterization underwent the procedure (62.3% in GUARANTEE tertiary centers vs. 44.6% in GUARANTEE nontertiary centers vs. 66.0% in TIMI, P < 0.001). CONCLUSION: After publication of clinical guidelines for UA/NSTEMI, more patients received appropriate pharmacologic treatment, but a significant number of patients remained under-treated. Efforts to improve compliance with guideline recommendations via education and critical pathways are warranted, especially in nontertiary care settings.