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Anatoly Langer

Publications and source records attributed to Anatoly Langer.

At least 37 records · Page 2Linked to original sources
PubMed2005

High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial.

CONTEXT: The SYNERGY trial comparing enoxaparin and unfractionated heparin in high-risk patients with acute coronary syndromes (ACS) showed that enoxaparin was not inferior to unfractionated heparin in reducing death or nonfatal myocardial infarction (MI) at 30 days. OBJECTIVE: To evaluate continued risk in this patient cohort through 6-month and 1-year follow-up. DESIGN, SETTING, AND PATIENTS: Overall, 9978 patients were randomized from August 2001 through December 2003 in 487 hospitals in 12 countries. Patients were followed up for 6 months and for 1 year. MAIN OUTCOME MEASURES: Six-month outcomes were death, nonfatal MI, revascularization procedures, stroke, and site-investigator-reported need for rehospitalization; 1-year outcome was all-cause death. RESULTS: Six-month and 1-year follow-up data were available for 9957 (99.8%) and 9608 (96.3%) of 9978 patients, respectively; 541 patients (5.4%) had died at 6 months and 739 (7.4%) at 1 year. Death or nonfatal MI at 6 months occurred in 872 patients receiving enoxaparin (17.6%) vs 884 receiving unfractionated heparin (17.8%) (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.89-1.07; P = .65). In the subgroup of patients receiving consistent therapy, ie, only enoxaparin or unfractionated heparin during the index hospitalization (n = 6138), a reduction in death or nonfatal MI with enoxaparin was maintained at 180 days (HR, 0.85; 95% CI, 0.75-0.95; P = .006). Rehospitalization within 180 days occurred in 858 patients receiving enoxaparin (17.9%) and 911 receiving unfractionated heparin (19.0%) (HR, 0.94; 95% CI, 0.85-1.03; P = .17). One-year all-cause death rates were similar in the 2 treatment groups (380/4974 [7.6%] for enoxaparin vs 359/4948 [7.3%] for unfractionated heparin; HR, 1.06; 95% CI, 0.92-1.22; P = .44). One-year death rates in patients receiving consistent therapy were also similar (251/3386 [7.4%] for enoxaparin vs 213/2720 [7.8%] for unfractionated heparin; HR, 0.95; 95% CI, 0.79-1.14; P = .55). CONCLUSIONS: In the SYNERGY trial, patients continued to experience adverse cardiac events through long-term follow-up. The effect of enoxaparin on death or MI compared with that of unfractionated heparin at 6 months was similar to that observed at 30 days in the overall trial and in the consistent-therapy group. One-year death rates were also similar in both groups. High-risk patients with ACS remain susceptible to continued cardiac events despite aggressive therapies.ClinicalTrials.gov Identifier: NCT00043784.

Enoxaparin↗
PubMed2005

In-hospital revascularization and one-year outcome of acute coronary syndrome patients stratified by the GRACE risk score.

In the prospective, multicenter Canadian Acute Coronary Syndromes Registry, in-hospital revascularization was independently associated with better 1-year survival only among patients with high-risk non-ST-elevation acute coronary syndromes stratified by the Global Registry of Acute Coronary Events risk score; similar benefits were not observed in the low- and intermediate-risk groups. The Global Registry of Acute Coronary Events risk score appears to be a useful risk stratification tool that identifies high-risk patients for whom more aggressive treatment is warranted.

Aged↗
PubMed2005

Enoxaparin and percutaneous coronary intervention: a Canadian perspective.

BACKGROUND: The low molecular weight heparin enoxaparin is commonly used in the management of patients with non-ST segment elevation acute coronary syndromes (ACS). It is perceived that there is variable acceptance of the use of enoxaparin in patients with ACS in conjunction with percutaneous coronary intervention (PCI) by Canadian interventional cardiologists, as well as diverse approaches to the procedural (ie, PCI) management of anticoagulation. METHODS AND RESULTS: A survey assessing physician and centre demographics, as well as the opinion and approach to the use of enoxaparin in patients undergoing PCI, was developed. All 141 interventional cardiologists performing PCI in Canada were sent the survey, with a 52% response rate. The majority (64%) of respondents were comfortable performing PCI during enoxaparin treatment, but almost one-half (46.5%) stated a preference to have a point-of-care measurement of the anticoagulation level during the procedure. Various 'top-up' protocols are used across the country, including fixed-dose intravenous (IV) enoxaparin, weight-adjusted IV enoxaparin, fixed-dose IV unfractionated heparin, weight-adjusted IV unfractionated heparin and IV unfractionated heparin titrated to a target activated clotting time. Although the median time threshold for administering a 'top-up' dose of anticoagulation matched current recommendations, there was a wide variation ranging from 2 h to 10 h (median 8 h). CONCLUSIONS: Although the majority of Canadian interventional cardiologists were comfortable performing PCI in patients treated with enoxaparin, the survey demonstrated various levels of confidence and a diverse range of 'top-up' anticoagulation procedures. Nationwide guidelines for the management of anticoagulation in patients with ACS undergoing PCI with enoxaparin should be developed from the best available clinical and research evidence to limit potential patient risk of inadequate or excessive anticoagulation. This is especially relevant in view of the association between switching among anticoagulant therapies and an increased bleeding risk in patients undergoing early cardiac catheterization and PCI that was found in the recently reported Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial.

Angina, Unstable↗
PubMed2005

Comparison of ST-segment resolution with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy versus fibrinolytic alone (data from four clinical trials).

We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with >/=50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed.

Abciximab↗
PubMed2005

Early cardiac catheterization is associated with lower mortality only among high-risk patients with ST- and non-ST-elevation acute coronary syndromes: observations from the OPUS-TIMI 16 trial.

BACKGROUND: Early cardiac catheterization has been shown to improve outcomes in patients with non-ST-elevation acute coronary syndromes but not yet in those with ST-elevation myocardial infarction (STEMI). The benefit of catheterization in both syndromes may depend on patient risk for adverse clinical outcomes. METHODS: We analyzed the relation between inhospital catheterization and subsequent clinical outcomes based on risk profile in 8286 patients in the OPUS-TIMI 16 Trial of patients with acute coronary syndromes. Using baseline clinical characteristics, patients were stratified into low-, intermediate-, and high-risk groups. The primary end point was 10-month mortality. The STEMI, non-STEMI (NSTEMI), and unstable angina subgroups were analyzed separately. RESULTS: Inhospital cardiac catheterization was performed in 44% of patients. Mortality rates at 10 months were 1.3%, 2.2%, and 11.3% in the low-, intermediate-, and high-risk groups, respectively. Inhospital cardiac catheterization was associated with a trend to lower mortality among the high-risk patients with STEMI (hazard ratios [HR] 0.57, 95% CI 0.33-1.01, P = .052) and NSTEMI (HR 0.65, 95% CI 0.39-1.07, P = .088) but not in those with unstable angina (HR 0.95, 95% CI 0.63-1.43, P = .82). Catheterization was not associated with any significant difference in mortality in the low-risk or intermediate-risk group. The differences among high-risk patients persisted after adjusting for baseline characteristics; inhospital catheterization was associated with significantly lower mortality in high-risk patients with ST and non-ST myocardial infarction (HR 0.65, 95% CI 0.45-0.95, P = .03). CONCLUSIONS: Inhospital cardiac catheterization is associated with lower mortality in high-risk patients and no difference in mortality in low-risk and intermediate-risk patients after STEMI and NSTEMI. These data support the hypothesis that high-risk patients with either STEMI or NSTEMI may benefit from an early invasive strategy. New prospective randomized trials are warranted, particularly in the STEMI population.

Aged↗
PubMed2005

Predictors and 1-year outcome of major bleeding in patients with non-ST-elevation acute coronary syndromes: insights from the Canadian Acute Coronary Syndrome Registries.

BACKGROUND: Bleeding is the major noncardiac adverse consequence of treatment in patients with non-ST-elevation (NSTE) acute coronary syndromes (ACS). The aims were to identify predictors of major bleeding in patients with NSTE ACS and to evaluate in-hospital and 1-year outcomes. METHODS: We evaluated 5842 patients with NSTE-ACS included in the multicenter Canadian ACS Registries. RESULTS: Patients with in-hospital major bleeding (n = 79, 1.4%) were older (75 vs 66 years, P < .001), with higher baseline creatinine (1.17 vs 1.02 mg/dL, P < .002), more diabetes (36% vs 25%, P = .04), hypertension (73% vs 54%, P < .002), previous stroke (20% vs 9%, P < .002), Killip class > or = II (P < .01), and ST-depression (37% vs 18%, P < .001). Antiplatelet/thrombotic therapies did not differ between patients with and without major bleeding. Crude event rates were significantly higher in patients with major bleeding: in-hospital death 19.2% vs 1.5% (P < .001), myocardial infarction (MI) 15.4% vs 3.8% (P < .001), and death or MI 26.9% vs 4.9% (P < .001). One-year event rates were also higher: death 35.9% vs 7.4% (P < .0001), MI 15.6% vs 6.2% (P = .0021), and death or MI 40.6% vs 12.6% (P < .0001). In multivariable analysis, independent predictors for major bleeding were age (OR 1.03, 95% CI 1.03-1.09), hypertension (1.72, 1.0-2.97), previous stroke (1.84, 1.0-3.37), and in-hospital catheterization (1.93, 1.06-3.53) or bypass surgery (2.18, 1.0-4.76). Major bleeding was an independent predictor of 1-year death (OR 3.92, 2.07-7.41) and death or MI (2.51, 1.41-4.48). CONCLUSIONS: In patients with NSTE-ACS, major bleeding is associated with increased short- and long-term rates of death and MI, and is predicted by simple clinical characteristics.

Acute Disease↗
PubMed2005

Are Canadian guidelines for cholesterol lowering in high-risk patients optimal?

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.

Atorvastatin↗
PubMed2004

Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial.

CONTEXT: Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. OBJECTIVES: To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. DESIGN, SETTING, AND PARTICIPANTS: The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. INTERVENTIONS: Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. MAIN OUTCOME MEASURES: The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. RESULTS: The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). CONCLUSIONS: Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.

Aged↗
PubMed2004

Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview.

CONTEXT: Antithrombin therapy has become a guidelines-recommended standard of care in the treatment of acute coronary syndromes (ACS), but recent trials comparing use of enoxaparin and unfractionated heparin in ACS have yielded less robust efficacy and safety results than have earlier trials of these antithrombin therapies. OBJECTIVE: To systematically evaluate the end points of all-cause death and nonfatal myocardial infarction (MI), transfusion, and major bleeding observed in the 6 randomized controlled trials comparing enoxaparin and unfractionated heparin in treatment of ACS. DATA SOURCES: The primary data sets for ESSENCE, A to Z, and SYNERGY were available at the Duke Clinical Research Institute. Baseline characteristics and event frequencies for TIMI 11B, ACUTE II, and INTERACT were provided by the principal investigator of each study. STUDY SELECTION: All 6 randomized controlled trials comparing enoxaparin and unfractionated heparin in non-ST-segment elevation ACS were selected for analysis. DATA EXTRACTION: Efficacy and safety end points were extracted from the overall trial populations and the subpopulation receiving no antithrombin therapy prior to randomization. DATA SYNTHESIS: Systematic evaluation of the outcomes for 21 946 patients was performed using a random-effects empirical Bayes model. No significant difference was found in death at 30 days for enoxaparin vs unfractionated heparin (3.0% vs 3.0%; odds ratio [OR], 1.00; 95% confidence interval [CI], 0.85-1.17). A statistically significant reduction in the combined end point of death or nonfatal MI at 30 days was observed for enoxaparin vs unfractionated heparin in the overall trial populations (10.1% vs 11.0%; OR, 0.91; 95% CI, 0.83-0.99; number needed to treat, 107). A statistically significant reduction in the combined end point of death or MI at 30 days was also observed for enoxaparin in the populations receiving no prerandomization antithrombin therapy (8.0% vs 9.4%; OR, 0.81; 95% CI, 0.70-0.94; number needed to treat, 72). No significant difference was found in blood transfusion (OR, 1.01; 95% CI, 0.89-1.14) or major bleeding (OR, 1.04; 95% CI, 0.83-1.30) at 7 days after randomization in the overall safety population or in the population of patients receiving no prerandomization antithrombin therapy. CONCLUSION: In a systematic overview of approximately 22 000 patients across the spectrum of ACS, enoxaparin is more effective than unfractionated heparin in preventing the combined end point of death or MI.

Angina Pectoris↗
PubMed2004

One-year outcome of patients after acute coronary syndromes (from the Canadian Acute Coronary Syndromes Registry).

The objective of this study was to determine the management and outcome of less [corrected] selected patients with an acute coronary syndrome during hospitalization and up to 1 year after discharge. The Canadian Acute Coronary Syndromes Registry was a prospective observational study of patients admitted with suspected acute coronary syndromes. Data on demographic and clinical characteristics, in-hospital treatment, and outcomes were recorded. At 1 year, vital status, medication use, recurrent cardiac events, and procedures were determined by telephone contact. Of the 5,312 patients enrolled, 4,627 had a final diagnosis of acute coronary syndrome, with Q-wave myocardial infarction in 27.7%, non-Q-wave myocardial infarction in 33.2%, and unstable angina pectoris in 39.1%. During hospitalization, coronary angiography and revascularization were performed in 39.6% and 20.3% of patients, respectively. The in-hospital mortality rate was 2.4% overall. At discharge, 87.8%, 76.4%, 56.0%, and 54.8% of patients were prescribed aspirin, beta blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering agents, respectively. Unadjusted 1-year mortality rates for hospital survivors were 6.5%, 10%, and 5.4% for those with Q-wave myocardial infarction, non-Q-wave myocardial infarction, and unstable angina pectoris groups, respectively (p <0.0001). This difference in mortality rate remained significant after adjusting for other prognosticators, whereas the use of coronary angiography and revascularization after discharge was similar across patients. At 1 year, fewer patients were maintained on aspirin and beta blockers, whereas the use of lipid-lowering therapy increased (all p <0.0001). Despite similar rates of coronary angiography and revascularization after discharge, patients with non-Q-wave myocardial infarction had worse outcomes at 1 year. Moreover, there was a significant opportunity to enhance the discharge and long-term use of evidence-based secondary prevention therapies.

Aged↗
PubMed2004

Combining baseline clinical descriptors and real-time response to therapy: the incremental prognostic value of continuous ST-segment monitoring in acute myocardial infarction.

BACKGROUND: Clinical descriptors and ST-segment recovery variables hold prognostic information for clinical outcome after thrombolysis for acute myocardial infarction (MI). We sought to define the incremental prognostic value of continuous 12-lead ST-segment monitoring variables to clinical risk descriptors identified by the Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial 30-day mortality analysis. METHODS: Of 1,777 patients enrolled in continuous ST-segment substudies from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-9), GUSTO-I, Duke University Clinical Cardiology Study (DUCCS-II), Integrilin to manage Platelet Aggregation to Combat Thrombus in Acute Myocardial Infarction (IMPACT-AMI), Promotion of Reperfusion by Inhibition of Thrombin During Myocardial Infarction Evolution (PRIME), and Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) trials, 825 patients qualified for assessment of time to recovery. ST recovery variables analyzed were time to stable ST-recovery and late ST elevation. Patients who were at low clinical risk (n = 261) had no high-risk descriptors, and patients at high clinical risk (n = 564) had at least 1 of these high-risk descriptors: age >or=70 years, systolic blood pressure or=90 beats/min, anterior MI, or previous MI. High (n = 90), moderate (n = 318), and low (n =417) ST-risk groups were defined by the presence of both slow ST recovery and late ST elevation, one or the other, or neither, respectively. End points analyzed were inhospital death and combined death, reinfarction, or congestive heart failure. RESULTS: There was a trend toward increased mortality rate in the high-clinical/high-ST-risk group. For the composite end point, ST subgrouping resulted in significant event stratification in both patients at low and high clinical risk. In multivariable analysis, age and heart rate were independent predictors of both mortality and the composite end point. Late ST elevation added incremental prognostic information. CONCLUSION: Age, heart rate, and late ST elevation are powerful, independent predictors of adverse clinical outcome. Continuous monitoring allows noninvasive assessment of the response to therapy. Consequently, this technique will enhance the potential to risk-stratify individual patients in a real-time setting.

Aged↗
PubMed2004

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.

Adult↗
PubMed2004

How does the prognosis of diabetes compare with that of established vascular disease? Insights from the Canadian Vascular Protection (VP) Registry.

BACKGROUND: Diabetes mellitus is a major risk factor for atherosclerotic cardiovascular disease. In a large, prospective, practice-based registry (the Vascular Protection Registry), we enrolled patients with vascular disease and/or diabetes, and compared the following features between diabetic and non-diabetic participants: (1) risk factor profiles, (2) utilization of cardioprotective medications, and (3) cardiovascular outcomes in short-term follow-up. METHODS: Patients were enrolled by participating physicians practicing in family medicine or specialty practices across Canada. The primary outcome was a composite of the first occurrence of any of the following vascular events: myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, or death. Patients were stratified according to the presence or absence of cardiovascular disease and diabetes. RESULTS: In all, 3297 patients were available for analysis (972 [30%] with diabetes but no cardiovascular disease; 899 [27%] with both diabetes and cardiovascular disease; and 1425 [43%] with cardiovascular disease but no diabetes). Most of the measured risk factors were worse for patients with diabetes. Compared to non-diabetic patients, diabetes was associated with substantial undertreatment with cardioprotective medications, including antiplatelet agents, beta blockers, and statins. During a mean follow-up of 10 (SD 3.3) months, patients with both diabetes and cardiovascular disease had the worst prognosis, with the primary outcome occurring at a rate of 16.3 per 100 person-years of follow-up. CONCLUSIONS: Patient registries provide a powerful tool for examining treatment patterns, risk factors, and outcomes. Patients with both cardiovascular disease and diabetes had the highest rates of adverse vascular outcomes. Possible reasons include relatively worse risk factor profiles and undertreatment with proven cardiovascular medications.

Aged↗
PubMed2004

Troponin is more useful than creatine kinase in predicting one-year mortality among acute coronary syndrome patients.

AIMS: To compare the long-term prognostic value of troponins (Tn) vs. conventional cardiac biomarker creatine kinase (CK) and CK-MB across the spectrum of acute coronary syndromes (ACS). METHODS AND RESULTS: In the prospective, observational Canadian ACS Registry, 4627 patients with ACS were enrolled from 51 centres. The CK, CK-MB, Tn samples were analysed in each hospital clinical laboratory and the results related to the reference levels of the individual laboratories. The study cohort comprised 3138 (67.8%) patients who had both CK (or CK-MB) and Tn measurements during the first 24 h of hospitalisation. Vital status at one-year was determined by standardized telephone interview. 61.2% and 59.0% of patients had abnormal Tn and CK (or CK-MB) levels, respectively. Vital status at one-year was ascertained for 2950 patients (6% lost to follow-up). Among patients with normal CK (or CK-MB) levels, elevated Tn was associated with increased one-year mortality (odds ratio [OR] 2.06; 95% CI 1.37-3.11; P=0.001). Similarly, among patients with abnormal CK (or CK-MB) levels, abnormal Tn predicted higher one-year mortality (OR 1.83; 95% CI 1.14-2.93; P=0.01). In contrast, abnormal CK (or CK-MB) was not predictive of mortality after stratification by Tn status. In multivariable analysis controlling for other known prognosticators including creatinine, abnormal Tn (adjusted OR 1.78; 95% CI 1.30-2.44; P<0.001) but not CK/CK-MB was independently associated with increased one-year mortality. CONCLUSIONS: Elevated Tn was independently associated with worse outcome at one-year, while CK or CK-MB status did not provide incremental prognostic information. Our findings support the use of Tn in the risk stratification of unselected ACS patients.

Aged↗
PubMed2004

Relationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.

BACKGROUND: Although available guidelines suggest reducing low-density lipoprotein cholesterol (LDL-C) to below 100 mg/dL (2.6 mmol/L), the importance of target-oriented therapy remains controversial. To assess whether achieving guideline-based targets is of benefit, the relationship between clinical outcomes and lipid levels (baseline and on-study) was evaluated in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. This study demonstrated significant reductions in morbidity and mortality associated with active dose titration of atorvastatin and structured management of dyslipidaemia. METHODS AND RESULTS: Intention-to-treat analysis (Cox proportional hazards model) was used to assess the relationship between lipid values and coronary events. Higher levels of LDL-C at baseline were associated with a greater risk of subsequent events among patients randomized to usual care. Reducing the LDL-C and the non-high density lipoprotein cholesterol (non-HDL-C) level to the National Cholesterol Educational Program (NCEP) Adult Treatment Panel (ATP) III goals required greater doses of atorvastatin for the higher baseline quartile of LDL-C. During the study there was a greater reduction in the risk of coronary heart disease (CHD) events in atorvastatin-treated patients who were in the highest quartile of LDL-C at baseline, after achieving the LDL-C treatment goal, in comparison to the usual care patients in the highest baseline LDL-C quartile. CONCLUSIONS: Achieving the NCEP ATP III LDL-C and non-HDL-C goals by titrating up the dose of atorvastatin was associated with a significant reduction in vascular events in patients with CHD. The greatest benefit was seen in those patients with the highest baseline LDL-C levels.

Aged↗
PubMed2004

A pharmacoeconomic evaluation of the myocardial ischemia reduction with aggressive cholesterol lowering (MIRACL) study in Canada.

OBJECTIVE: To determine a 16-week total healthcare cost and the cost-effectiveness of short-term, lipid-lowering therapy with atorvastatin 80 mg following acute coronary syndrome (ACS) in Canada. METHODS: The expected costs per patient on atorvastatin 80 mg per day and placebo were compared using clinical outcome data from the MIRACL study and cost data from the Ontario Case Costing Project and the Ontario Schedule of Benefits. The cost per event avoided was also assessed. The clinical outcomes measured included: death, cardiac arrest, non-fatal myocardial infarction (MI), fatal MI, angina pectoris, stroke, congestive heart failure, and surgical or percutaneous coronary revascularizations. All direct medical costs from the perspective of the Canadian health care system were taken into account. RESULTS: The total expected cost per patient was 2,590 dollars in the placebo group and 2,639 dollars in the atorvastatin group. The incremental cost of atorvastatin treatment (49.26 dollars per patient) corresponded to a cost of 1,285 dollars per event avoided. The cost savings obtained through the reduction in events offset 86% of the cost of atorvastatin treatment. Budget impact analysis revealed that increased rates of atorvastatin usage following ACS were associated with large numbers of events avoided at a small additional cost when projected to the Canadian population. CONCLUSIONS: In Canada, the clinical benefits of intensive short-term atorvastatin treatment administered within 96 hours after ACS were associated with a favorable cost-effectiveness ratio. The incremental cost of atorvastatin is mostly offset by savings due to the reduction in events in patients treated with atorvastatin.

Anticholesteremic Agents↗
PubMed2003

Randomized evaluation of the safety and efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide.

BACKGROUND: Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy. METHODS AND RESULTS: We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U x kg(-1) x h(-1) infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180- microg/kg bolus; 2 microg x kg(-1) x min(-1) infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, P=0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P=0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, P=0.0002) and subsequent (12.7% versus 25.9%, P<0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P=0.031). CONCLUSIONS: When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.

Acute Disease↗