Biomedical subjects

Anatoly Langer

Publications and source records attributed to Anatoly Langer.

At least 19 recordsLinked to original sources

PubMed2007

Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal.

OBJECTIVES: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high-risk patients with acute coronary syndromes (ACS). BACKGROUND: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. METHODS: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. RESULTS: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P=0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)-related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for >or=8 Fr (P<0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. CONCLUSIONS: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.

Aged↗

PubMed2006

Comparison of effectiveness of enoxaparin versus unfractionated heparin to reduce silent and clinically apparent acute myocardial infarction in patients presenting with non-ST-segment elevation acute coronary syndrome.

Electrocardiographic (ECG) estimates of myocardial infarct size based on the Selvester ECG score have been shown to predict mortality and left ventricular function after acute myocardial infarction (AMI). This score has also been used to identify not clinically apparent AMI ("silent" AMI) and to determine treatment effect, suggesting it could serve as a clinical trial end point. The objective of this study was to compare the rate of silent AMI as measured by the Selvester QRS score in patients with a non-ST-segment elevation acute coronary syndrome treated with enoxaparin versus intravenous unfractionated heparin who were participating in a continuous ECG monitoring substudy of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study (ESSENCE) and INTegrelin and Enoxaparin Randomized Assessment of acute Coronary syndrome Treatment trial (INTERACT). Enoxaparin was associated with a 56% relative risk decrease in silent AMI at 96 hours compared with unfractionated heparin (2.7% vs 6.1% p = 0.03). Similarly, enoxaparin decreased Holter-detected myocardial ischemia compared with unfractionated heparin (18.7% vs 35.9%, p = 0.03). In conclusion, enoxaparin significantly decreased the composite of silent AMI or clinical AMI and death at 1 year (9.3% vs 21%, p = 0.0001).

Anticoagulants↗

PubMed2006

Increased soluble Fas plasma levels in subjects at high cardiovascular risk: Atorvastatin on Inflammatory Markers (AIM) study, a substudy of ACTFAST.

OBJECTIVE: Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment. METHODS AND RESULTS: ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk > 20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides < or = 600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL. CONCLUSIONS: sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.

Aged↗

PubMed2006

A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment. METHODS: Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.

Aged↗

PubMed2006

Supporting a call to action for peripheral artery disease: insights from two prospective clinical registries.

BACKGROUND: Patients affected by peripheral arterial disease (PAD) incur a heightened risk of adverse cardiovascular events, including stroke, myocardial infarction, and vascular mortality. We examined risk factors, medications, and prognosis of outpatients with PAD enrolled in two national, prospective, practice-based Canadian registries that encompassed 484 physician practices: the Vascular Protection and Guideline Oriented Approach in Lipid Lowering registries. METHODS: The 2 registries were combined to analyze 9810 patients with vascular disease, diabetes mellitus, or age 65 years or older plus at least 2 additional cardiovascular risk factors. Risk factors, medications, and major cardiovascular events were recorded at baseline and again at 6 months' follow-up. RESULTS: Compared with patients without PAD (n = 8303), those with PAD (n = 1507) had substantially worse risk factor profiles and were more likely to have coexisting coronary or cerebrovascular disease. Both groups received high rates of treatment with evidence-based therapies, including antiplatelet drugs, statins, and angiotensin-converting enzyme inhibitors. Despite this, patients with PAD had a nearly twofold higher risk of major cardiovascular events at 6 months than non-PAD patients (7.3% vs 4.1%; P < .0001). After adjustment for multiple confounding factors, the presence of PAD at baseline continued to predict a heightened risk of adverse vascular sequelae (odds ratio, 1.54; 95% confidence interval, 1.18-2.01; P < .0001). CONCLUSIONS: These data support a strong relationship between PAD and worsened vascular prognosis that is independent of both conventional vascular risk factors and concomitant cardiovascular disease. The presence of PAD should therefore provide a clear impetus for intensive risk factor modification and use of preventive medical therapy in affected patients.

Aged↗

PubMed2006

Prognostic significance of admission heart failure in patients with non-ST-elevation acute coronary syndromes (from the Canadian Acute Coronary Syndrome Registries).

We evaluated the in-hospital and 1-year outcomes and predictors of admission heart failure in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) without previous heart failure. We analyzed 4,825 patients with NSTE-ACS without a history of congestive heart failure who were included in the multicenter Canadian ACS Registries. Patients in Killip's class II/III on admission (n = 559, 11.6%) were compared with patients in Killip's class I. Patients with heart failure on admission were older (72 [64, 79] vs 64 [54, 73] years, p < 0.0001), with higher baseline creatinine levels (96 vs 88 mmol/dl, p <0.0001), more diabetes (32.2% vs 22.8%, p < 0.0001), hypertension (58% vs 52.4%, p = 0.014), previous myocardial infarction (MI; 38.9% vs 30.3%, p < 0.0001), previous stroke (13.5% vs 7.4%, p < 0.0001), and had more ST depression on admission (27.7% vs 17.3%, p < 0.0001). In-hospital treatment was similar except for a lower rate of aspirin therapy and fewer coronary interventions. Crude event rates were significantly higher in patients with heart failure (in-hospital death 3.6% vs 1.1%, p < 0.0001; death or MI 7.9% vs 4.7%, p = 0.0011; stroke 1.1% vs 0.4%, p = 0.03). One-year event rates were also higher in patients with heart failure (death 14.6% vs 4.4%, p < 0.0001; MI 9.3% vs 6.6%, p = 0.03; death or MI 21.5% vs 10.3%, p < 0.0001). Variables independently associated with heart failure were age (odds ratio 1.57, 95% confidence interval 1.43 to 1.73), diabetes mellitus (odds ratio 1.53, 95% confidence interval 1.24 to 1.89), admission ST depression (odds ratio 1.52, 95% confidence interval 1.22 to 1.90), previous MI, and baseline creatinine. Heart failure on admission was an independent predictor of in-hospital death, death or MI, and stroke and of 1-year death and death or MI. In conclusion, in patients with NSTE-ACS, heart failure on admission is associated with increased short- and long-term rates of death and MI.

Aged↗

PubMed2006

Age-related differences in the management and outcome of patients with acute coronary syndromes.

BACKGROUND: Age-related differences in patients with an acute coronary syndrome (ACS) have not been well characterized in prior observational studies that often included only certain age groups or subjects with myocardial infarction (MI). METHODS: We stratified 4627 patients admitted with an ACS across 9 provinces between 1999 and 2001 enrolled in the Canadian ACS Registry into 3 age groups (< 65, 65-74, and > or = 75 years) to evaluate differences in clinical characteristics, management, and 1-year outcome. RESULTS: Older patients more frequently had previous angina, MI, or heart failure and were less likely to have positive cardiac markers, ST elevation, and Q-wave MI or to receive thrombolytics, beta-blockers, and cholesterol-lowering and antiplatelet agents in hospital, at discharge, and at 1 year. In multivariable analyses controlling for patient factors, every decade increase in age was independently associated with reduced use of coronary angiography (odds ratio [OR] 0.79, 95% CI 0.74-0.84, P < .001) and percutaneous coronary intervention (OR 0.88, 95% CI 0.81-0.95, P = .001). When adjusted for validated clinical prognosticators and differences in management, every decade of age increment independently predicted an increased risk of death at 1 year (OR 1.87, 95% CI 1.66-2.12, P < .001). CONCLUSIONS: Across the broad spectrum of ACS, elderly patients had more complex comorbidities and worse outcome, yet they were less likely to undergo revascularization or to receive acute and long-term evidence-based medications. Our findings emphasize the ongoing need to better define and promote optimal therapeutic regimens for elderly patients with ACS.

Age Factors↗

PubMed2006

Randomized evaluation of the 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. Long-term results of the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial.

BACKGROUND: Patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) benefit from the early administration of aspirin, a small molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin and eptifibatide, the use of enoxaparin compared with unfractionated heparin (UFH) was associated with less bleeding, less early myocardial ischemia, and improved 30-day outcomes. OBJECTIVE: The aim of our study was to determine whether the short-term benefits of enoxaparin compared with UFH observed in high-risk patients with NSTE ACS are maintained over a prolonged period of follow-up. METHODS: Six hundred thirty-nine patients that were representative of the total population of subjects in the INTERACT trial were followed up for a median period of 2.5 years. RESULTS: In this group, the early benefit of enoxaparin was maintained. The incidence of death or myocardial infarction at the time of long-term follow-up was 39% lower in patients receiving enoxaparin compared with those who received UFH (8.9% vs 14.7%, P = .024). There was no difference in the frequency of cardiac catheterization in the groups receiving either enoxaparin or UFH. CONCLUSIONS: The early treatment of high-risk patients with NSTE ACS receiving aspirin and eptifibatide with enoxaparin is associated with early outcome benefits that are sustained over a prolonged follow-up period. This trial supports the concept that early treatment directed against platelet and thrombin formation is associated with better short- and long-term outcomes.

Angina, Unstable↗

PubMed2006

The greatest benefit of enoxaparin over unfractionated heparin in acute coronary syndromes is achieved in patients presenting with ST-segment changes: the Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) Electrocardiogram Core Laboratory Substudy.

BACKGROUND: We undertook a prospective electrocardiogram (ECG) substudy in the ESSENCE trial and hypothesized that patient subgroups with ST-segment deviation would experience greater benefit from enoxaparin, as compared with unfractionated heparin (UFH). METHODS: Of the 3171 patients in the trial, 3087 had a qualifying ECG available for analysis by the core laboratory. Patients were divided into 4 mutually exclusive groups based upon the qualifying ECG: (1) ST-segment elevation, (2) ST-segment depression, (3) T-wave inversions, or (4) others. RESULTS: The 30-day and 1-year primary outcomes (death, myocardial infarction, or recurrent angina) were significantly lower among patients with ST elevation or ST depression who received enoxaparin, as compared with UFH (20.8% vs 28.0%, P = .0019 and 32% vs 40.4%, P = .0011, respectively). The greatest absolute benefit of enoxaparin over UFH was seen in patients with ST depression (primary end point at 30 days, 24.6% vs 32.4%, P = .018; at 1 year, 35.5% vs 44.5%, P = .012). CONCLUSION: Specific recognition of patients with ST-segment depression appears to identify those not only at high risk for adverse outcome, but also patients most likely to derive the greatest benefit from enoxaparin, as compared with UFH therapy.

Angina, Unstable↗

PubMed2006

ST-segment depression in non-ST elevation acute coronary syndromes: quantitative analysis may not provide incremental prognostic value beyond comprehensive risk stratification.

BACKGROUND: It is unclear whether quantitative ST-segment assessment can improve risk stratification of unselected acute coronary syndrome (ACS) patients using the validated Global Registry of Acute Cardiac Events (GRACE) risk model. METHODS: In the prospective, multicenter, Canadian ACS Registry, the admission electrocardiogram was evaluated centrally at a blinded core laboratory. Patients with ST-elevation myocardial infarction and other electrocardiogram confounders were excluded. ST depression (ST down) was measured and summed in all leads except aVR. Patients with ST down were divided into 3 groups based on tertiles of cumulative ST down. A multivariable model was developed to examine the independent prognostic value of ST down severity after adjusting for other known prognosticators in the GRACE risk model. RESULTS: Among 2590 patients with non-ST-elevation ACS, more severe ST down was associated with advanced age, higher heart rate and Killip class, elevated creatinine, abnormal biomarkers, higher GRACE risk score, and higher 1-year mortality (all P < .001). After adjusting for these confounding prognosticators, the presence of any ST down remained independently associated with higher 1-year mortality (odds ratio 1.78, 95% CI 1.21-2.63, P = .004). However, the gradient of risk with increasing magnitude of ST down was no longer evident (adjusted odds ratios 1.77, 1.77, 1.81, for ascending tertiles of cumulative ST down, respectively). Moreover, quantitative ST down did not improve the model discrimination for 1-year mortality. The results were similar when the number of leads with ST down or the maximum magnitude of ST down was analyzed, after adjusting for tertiles of GRACE risk score or inhospital revascularization, or using the composite end point of death or myocardial (re)infarction at 1 year. CONCLUSIONS: Greater ST down is associated with other adverse prognosticators across the broad spectrum of non-ST-elevation ACS. Although the presence of any ST down is an independent predictor of 1-year mortality, its quantitative assessment is not as important as its mere presence when studied on the background of comprehensive clinical and biomarker evaluation in a nonclinical trial-based ACS population.

Aged↗

PubMed2006

The prognostic value of the admission and predischarge electrocardiogram in acute coronary syndromes: the GUSTO-IIb ECG Core Laboratory experience.

BACKGROUND: Prior research suggests that patients may be entered into clinical trials with different electrocardiographic (ECG) findings than specified by study protocol criteria; the extent and impact of this variability in a large-scale trial have not been previously described. METHODS: We evaluated the relationship between case report form (CRF) categorization of the admission ECG and a Core Laboratory and subsequent outcome in a retrospective analysis of a trial of patients with acute ischemia and a broad spectrum of ECG changes (the GUSTO-IIb trial). RESULTS: In 11,037 patients with CRF information and an interpretable ECG, there was agreement in 89.1% of ST-elevation and 81.9% of non-ST-elevation cases. Among patients designated as having no ST elevation on the CRF, 1-year mortality rates were significantly higher in the subgroup of patients with Core Laboratory-determined ST elevation as compared with those where both the CRF and Core Laboratory classification were in agreement (8.8% vs 6.8%, P = .0093). Among patients designated as having ST elevation by the CRF, 1-year mortality rates were similar in both the subgroup of patients with and without Core Laboratory agreement (7.7% vs 8.2%, P = .72). CONCLUSIONS: These findings have important implications for clinicians in routine practice because even a simple evaluation (presence or absence of ST elevation) on the admission ECG was often discordant and was associated with adverse clinical outcome.

Aged↗

PubMed2006

Underuse of evidence-based treatment partly explains the worse clinical outcome in diabetic patients with acute coronary syndromes.

BACKGROUND: Diabetes-related differences in treatment and clinical outcome of patients across the entire spectrum of acute coronary syndromes (ACSs) have potential clinical implications but have not been well studied. METHODS: The multicenter, prospective, Canadian ACS Registry enrolled 4578 patients hospitalized for ACS between 1999 and 2001 across 9 provinces in Canada. We compared baseline characteristics, in-hospital and post-discharge treatments, and clinical outcome of diabetic and non-diabetic patients. The impact of diabetes on use of thrombolytic therapy and coronary revascularization; and the independent association between diabetes, treatments, and diabetes-treatment interactions on outcome were examined. RESULTS: Diabetic patients with ACS had more cardiovascular risk factors and higher-risk clinical presentation. They paradoxically received less evidence-based medications in-hospital, at discharge, and at 1-year. Although diabetes independently predicted higher 1-year mortality (OR 1.47, 95% CI 1.15-1.87; P = .002) after adjustment for validated prognosticators, it was also an independent predictor of not receiving thrombolytic therapy (OR 0.72, 95% CI 0.54-0.95; P = .021) and coronary revascularization (OR 0.69, 95% CI 0.59-0.82; P < .001). These underused therapies were all independently associated with reduced 1-year mortality, with no significant diabetes-related treatment-outcome heterogeneity. Importantly, diabetes remained an independent adverse prognosticator even after further adjustment for these differences in treatment. CONCLUSIONS: Evidence-based therapies are underused in the contemporary management of diabetic patients with ACS, which partly explains their worse outcome. Diabetes should be considered a high-risk feature in ACS risk stratification that encourages more intensive treatments. Continued efforts to promote adherence to existing proven therapies and to develop novel treatment strategies targeting diabetes-specific cardiovascular pathophysiology are imperative to improve their adverse prognosis.

Acute Disease↗

PubMed2006

Contemporary management of dyslipidemia in high-risk patients: targets still not met.

PURPOSE: Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients. METHODS: Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol<2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70 mg/dL]) for very high-risk patients. RESULTS: Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD (P<.0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P<.0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P<.0001). CONCLUSION: Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.

Aged↗

PubMed2006

Treatment and one-year outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes.

BACKGROUND: There are limited data on the treatment and long-term outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes (ACS) in Canada. OBJECTIVES: To examine the treatment patterns and outcome of ACS patients with renal dysfunction. METHODS: In the prospective, multicentre, Canadian ACS Registry, 3510 patients hospitalized for ACS (including unstable angina, ST and non-ST elevation myocardial infarction) were categorized into four groups: normal renal function (creatinine clearance [CrCl] 90 mL/min or greater; n=1152), mild renal dysfunction (CrCl 60 mL/min to 89 mL/min; n=1253), moderate renal dysfunction (CrCl 30 mL/min to 59 mL/min; n=944) and severe renal dysfunction (CrCl less than 30 mL/min; n=161). Multivariable logistic regression analysis was performed to examine the independent prognostic value of renal dysfunction, and the association of various therapies with one-year survival. RESULTS: All-cause mortality at one year was 2.8%, 6.4%, 14.5% and 40.9% in patients with normal renal function, and mild, moderate and severe renal dysfunction, respectively (P for trend<0.001). After adjusting for other prognosticators, moderate (OR 1.82, 95% CI 1.08 to 3.08) and severe (OR 6.29, 95% CI 3.37 to 11.77) renal dysfunction remained independent predictors of one-year death. Patients with renal dysfunction were less likely to receive fibrinolytic therapy, to undergo coronary angiography and revascularization in hospital, and to be treated with acetylsalicylic acid, beta-blockers and lipid-lowering therapy at discharge and at one-year follow-up. The association of in-hospital revascularization, and discharge use of acetylsalicylic acid and beta-blockers with better one-year survival was similar among patients with normal and impaired renal function. CONCLUSIONS: Renal dysfunction is prevalent and independently predicts higher mortality in patients with ACS. The current underutilization of effective therapies may contribute to the poor outcome. There remains an important opportunity to improve care in this high-risk population.

Acute Disease↗

PubMed2006

Lower is better: implications of the Treating to New Targets (TNT) study for Canadian patients.

Recent clinical trials have indicated that lowering low-density lipoprotein cholesterol (LDL-C) levels below currently recommended targets results in favourable surrogate and clinical end points. The Treating to New Targets (TNT) study now confirms that aggressive cholesterol lowering to a mean LDL-C of 2.0 mmol/L with atorvastatin 80 mg daily, compared with the previous target of 2.5 mmol/L with atorvastatin 10 mg daily, results in improved clinical outcomes in high-risk patients with coronary artery disease. A lower LDL-C target of less than 2.0 mmol/L will present therapeutic challenges, because approximately only one-half of high-risk patients will achieve this target using monotherapy with the newer and more powerful statins. Furthermore, registry data show that one-half of these patients are not even achieving the current LDL-C target of 2.5 mmol/L. Causes of the care gap are discussed and possible remedies to achieve the new lower targets are suggested.

Atorvastatin↗

PubMed2006

Non ST segment elevation acute coronary syndromes: A simplified risk-orientated algorithm.

Non-ST segment elevation acute coronary syndromes (NSTE ACS) include a clinical spectrum that ranges from unstable angina to NSTE myocardial infarction. Management goals aim to prevent recurrent ACS and improve long-term outcomes by choosing a treatment strategy according to an estimate of the risk of an adverse outcome. Recent registry data suggest that patients with NSTE ACS frequently do not receive recommended treatment, and that risk stratification is not used to determine either the choice of treatment or the speed of access to coronary angiography. The present article evaluates the evidence for recommended treatment using information from recent trials and guidelines published by the major cardiac organizations in Europe and North America. Using this information, a multidisciplinary group developed a simplified algorithm that uses risk stratification to select an optimal early management strategy. Long-term outcomes are improved by a multi-faceted vascular protection strategy that is initiated at the time of hospitalization for NSTE ACS.

Acute Disease↗

PubMed2006

Transfer for urgent percutaneous coronary intervention early after thrombolysis for ST-elevation myocardial infarction: the TRANSFER-AMI pilot feasibility study.

BACKGROUND: Most hospitals in Canada do not have percutaneous coronary intervention (PCI) facilities and use thrombolysis as reperfusion therapy for ST-elevation myocardial infarction (STEMI). Urgent PCI after thrombolysis may optimize reperfusion and prevent reinfarction and recurrent ischemia. OBJECTIVE: To determine the feasibility of transferring high-risk STEMI patients from community hospitals in Ontario to PCI centres for urgent PCI within 6 h of thrombolysis. METHODS: Patients with anterior or high-risk inferior STEMI received tenecteplase and were urgently transferred to PCI centres. PCI was performed if at least 70% stenosis was present in the infarct-related artery, regardless of flow, using coronary stents. Transfer of stable patients back to community hospitals was encouraged 24 h to 48 h after PCI. RESULTS: Eighteen patients were transferred and underwent PCI a median of 3.9 h (range 2.7 h to 6.4 h) after thrombolysis. No complications occurred during transfer. One death occurred that was related to failed reperfusion and cardiogenic shock. Minor access-site bleeding occurred in five patients. Fifteen patients were transferred back to their community hospitals within 24 h of PCI. There were no further deaths or reinfarctions at one-year follow-up. CONCLUSIONS: Transfer of high-risk STEMI patients for urgent PCI within 6 h after thrombolysis appears feasible. The randomized trial phase of the Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) will compare this strategy with standard treatment after thrombolysis.

Adult↗

PubMed2006

Bedtime administration of graded-release diltiazem in patients with inadequate BP control: a tolerability and efficacy study.

BACKGROUND: Achievement of target BP is a challenge in patients attending family practice. The long duration between administration of the last bedtime dose of antihypertensive medication and the physiologic early morning surge in BP makes it difficult to achieve satisfactory BP control. OBJECTIVE: To determine whether a new graded-release preparation of diltiazem (diltiazem XC), taken once daily at bedtime, will show an acceptable adverse-effect profile as well as improved BP control. STUDY DESIGN/SETTING: This is an open label, observational study in an ambulatory care setting. PATIENTS: 954 patients with mild to moderate hypertension and BP not at target levels were attended by 85 physicians. Group 1 patients were receiving a diltiazem preparation and group 2 patients were not receiving any diltiazem preparation at baseline. INTERVENTION: Group 1 patients were given diltiazem XC at the same dose as the prestudy diltiazem. Treatment with diltiazem XC 180 mg was initiated in group 2 patients. Diltiazem XC was taken once daily at bedtime in both groups. MAIN OUTCOME MEASURE: The predetermined main outcome measure was the development of adverse events with diltiazem XC when changing or adding the study medication. The secondary outcome measure was the proportion of patients who achieved target BP levels. RESULTS: Moderate or severe adverse events occurred in 8.7% of patients. Although 21.8% of patients reported either new or worsening adverse events after starting diltiazem XC, the large majority of adverse events were mild in severity. The most frequent moderate or severe adverse events were headache (2.0%) and constipation (1.7%). More patients in group 2 reported adverse events compared with patients in group 1. Target BP levels were achieved in 47.8% (95% CI 44.3, 51.3) of patients completing the 8- to 12-week treatment. No difference was found in the proportion of patients at target BP levels in groups 1 and 2. CONCLUSION: Diltiazem XC, when used in an ambulatory care setting for patients who have not achieved BP targets, shows an acceptable adverse-effect profile and results in an important improvement of BP control.

Aged↗