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Biomedical subjects

Keith A A Fox

Publications and source records attributed to Keith A A Fox.

At least 19 recordsLinked to original sources
PubMed2007

Use of heparins in Non-ST-elevation acute coronary syndromes.

PURPOSE: We describe the use of antithrombotic therapy in the management of patients with acute coronary syndromes. METHODS: Patients from the Global Registry of Acute Coronary Events, a multinational coronary disease registry, were characterized according to the early and continued use of low-molecular-weight heparin, unfractionated heparin, any crossover of heparin therapy (change in early vs late heparin treatment), and no heparin treatment. Hospital outcomes were analyzed according to the heparin treatment and the timing of percutaneous coronary interventions. RESULTS: Data from 23,172 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. A total of 8791 patients were treated with low-molecular-weight heparin within the first 24 hours and continued thereafter; 4076 patients received unfractionated heparin; 2953 patients received neither heparin therapy; and 7352 patients received crossover heparin treatment. Concomitant treatment, including early or late percutaneous coronary intervention, varied according to the type of heparin therapy. Patients treated with a crossover therapy were more likely to undergo percutaneous coronary intervention. The rates of major bleeding and death were lower with low-molecular-weight heparin (1.4% and 1.8%, respectively) compared with unfractionated heparin (1.9% and 2.5%, respectively), crossover heparin (2.0% and 2.3%, respectively), or neither heparin (1.5% and 2.4%, respectively). CONCLUSIONS: There is significant variability in heparin use in patients with acute coronary syndromes. Heparin type and use seem to be related to the timing and use of percutaneous coronary interventions. The early use of low-molecular-weight heparin in the setting of an acute coronary syndrome is associated with better short-term outcomes.

Aged↗
PubMed2006

Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).

OBJECTIVE: To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with acute coronary syndrome. DESIGN: Prospective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation. SETTING: Ninety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand. POPULATION: 43,810 patients (21,688 in derivation set; 22,122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005. MAIN OUTCOME MEASURES: Death and myocardial infarction. RESULTS: 1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries). CONCLUSIONS: This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.

Epidemiologic Methods↗
PubMed2006

Direct vascular effects of protease-activated receptor type 1 agonism in vivo in humans.

BACKGROUND: Protease-activated receptor type 1 (PAR-1) has been proposed as the principal thrombin receptor in humans, although its actions in vivo have not been defined. The aim of the present study was to determine the direct vascular actions of PAR-1 agonism in humans. METHODS AND RESULTS: Dorsal hand vein diameter was measured by the Aellig technique in 14 healthy volunteers during local intravenous SFLLRN (PAR-1 agonist; 0.05 to 15 nmol/min) and SLIGKV (PAR-2 agonist; 1.6 to 160 nmol/min) infusions. The venous effects of SFLLRN were further assessed in the presence or absence of norepinephrine or the glycoprotein IIb/IIIa antagonist tirofiban. Forearm blood flow was measured by venous occlusion plethysmography in 16 volunteers during infusion of SFLLRN (1 to 50 nmol/min), SLIGKV (160 to 800 nmol/min), and the endothelium-dependent vasodilator bradykinin (100 to 1000 pmol/min). Platelet-monocyte binding (a sensitive measure of platelet activation) and plasma tissue plasminogen activator (tPA), plasminogen-activator inhibitor 1, and von Willebrand factor concentrations were measured at intervals throughout the study. SFLLRN caused dose-dependent venoconstriction (P<0.001) that was unaffected by norepinephrine or tirofiban co-infusion. In forearm resistance vessels, SFLLRN increased forearm blood flow (P<0.001), tPA release (P<0.001), and platelet-monocyte binding (P<0.0001) without affecting plasma plasminogen-activator inhibitor 1 or von Willebrand factor concentrations. SLIGKV caused venous (P<0.001) and arterial (P<0.01) dilatation without tPA release. CONCLUSIONS: We have demonstrated that PAR-1 agonism causes platelet activation, venous constriction, arterial dilatation, and tPA release in vivo in humans. These unique and contrasting effects provide important insights into the physiological and pathophysiological role of thrombin in the human venous and arterial circulations.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Adverse impact of bleeding on prognosis in patients with acute coronary syndromes.

BACKGROUND: The use of multiple antithrombotic drugs and aggressive invasive strategies has increased the risk of major bleeding in acute coronary syndrome (ACS) patients. It is not known to what extent bleeding determines clinical outcome. METHODS AND RESULTS: Using Cox proportional-hazards modeling, we examined the association between bleeding and death or ischemic events in 34,146 patients with ACS enrolled in the Organization to Assess Ischemic Syndromes and the Clopidogrel in Unstable Angina to Prevent Recurrent Events studies. Patients with major bleeding were older, more often had diabetes or a history of stroke, had a lower blood pressure and higher serum creatinine, more often had ST-segment changes on the presenting ECG, and had a 5-fold-higher incidence of death during the first 30 days (12.8% versus 2.5%; P < 0.0001) and a 1.5-fold-higher incidence of death between 30 days and 6 months (4.6% versus 2.9%; P = 0.002). Major bleeding was independently associated with an increased hazard of death during the first 30 days (hazard ratio, 5.37; 95% CI, 3.97 to 7.26; P < 0.0001), but the hazard was much weaker after 30 days (hazard ratio, 1.54; 95% CI, 1.01 to 2.36; P = 0.047). The association was consistent across subgroups according to cointerventions during hospitalization, and there was an increasing risk of death with increasing severity of bleeding (minor less than major less than life-threatening; P for trend = 0.0009). A similar association was evident between major bleeding and ischemic events, including myocardial infarction and stroke. CONCLUSIONS: In ACS patients without persistent ST-segment elevation, there is a strong, consistent, temporal, and dose-related association between bleeding and death. These data should lead to greater awareness of the prognostic importance of bleeding in ACS and should prompt evaluation of strategies to reduce bleeding and thereby improve clinical outcomes.

Acute Disease↗
PubMed2006

Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial.

CONTEXT: Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. OBJECTIVE: To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. MAIN OUTCOME MEASURES: Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). RESULTS: Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days. CONCLUSION: In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00064428.

Aged↗
PubMed2006

Comparison of fondaparinux and enoxaparin in acute coronary syndromes.

BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).

Aged↗
PubMed2006

Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction.

BACKGROUND: Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. METHODS: We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. RESULTS: The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group (17 percent reduction in relative risk, P<0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving enoxaparin (33 percent reduction in relative risk, P<0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given enoxaparin (P=0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given enoxaparin (P<0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P<0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given enoxaparin (P<0.001). CONCLUSIONS: In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit. (ClinicalTrials.gov number, NCT00077792.).

Aged↗
PubMed2006

Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.

BACKGROUND: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.).

Adult↗
PubMed2006

Heart rate turbulence and death due to cardiac decompensation in patients with chronic heart failure.

BACKGROUND: As treatment strategies for patients with chronic heart failure (HF) become more sophisticated, identifying patients at high risk of death and predicting mode of death is important. The aim of this study was to explore the potential utility of heart rate turbulence (HRT) to identify patients with HF at high risk of death. METHODS AND RESULTS: In a prospective study, 553 ambulant outpatients age 63+/-10 with symptoms of HF and evidence of cardiac dysfunction were recruited. All patients underwent 24-h Holter ECG recordings, which were analysed for arrhythmias, heart rate variability and HRT a measurement that is thought to quantify cardiac autonomic regulatory mechanisms. Baseline chest radiograph, biochemistry and 12-lead electrocardiograms were also obtained. In patients with HRT measurements at 5 years follow up, 146 patients had died, 59 due to decompensated HF. Independent predictors of death from decompensated HF at 5-year follow up (Cox proportional hazard model) were HRT slope (HR for 10% increment 0.84, 95% CI 0.77-0.91), serum sodium (HR for 10% increment 0.75, 95% CI 0.62-0.91) and serum creatinine (for 10% increment HR 1.14, 95% CI 1.08-1.19) all P<0.01. These 3 variables combined had excellent discrimination between patients dying of decompensated HF and other patients, C-statistic=0.82. CONCLUSIONS: In patients with mild-to-moderate HF, HRT slope is an independent predictor of death due to decompensated HF. HRT may have the potential to help tailor therapy in this patient group.

Aged↗
PubMed2006

The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE).

BACKGROUND: The impact and prognostic value of the redefinition of myocardial infarction (MI) with more sensitive markers have not been evaluated prospectively in a large, less selected population with acute coronary syndrome (ACS). METHODS: We evaluated the attack and case-fatality rates of MI based on initial and/or peak creatine kinase (CK), creatine kinase-MB (CK-MB), and cardiac troponin (the upper limit of normal [ULN] was defined according to the local hospital's standard) in a prospective observational registry of 26,267 patients with ACS admitted to 106 hospitals in 14 countries. RESULTS: The addition of cardiac troponin-positive status to CK status as a criterion for the diagnosis of MI resulted in as many as 1 in 4 additional patients meeting the redefined criteria. Compared with patients without elevated levels of CK and cardiac troponin, the crude odds for dying during hospitalization were significantly higher for patients with elevated troponin but not CK levels of greater than or equal to the ULN (odds ratio [OR] 2.2, 95% CI 1.6-2.9), those without CK levels >2 times the ULN (OR 2.8, 95% CI 2.2-3.5), and those with nonelevated levels of CK-MB (OR 2.1, 95% CI 1.4-3.2). The addition of cardiac troponin-positive status significantly increased the multivariable-adjusted odds for hospital death in patients with CK < or =2 times the ULN (OR 1.6, 95% CI 1.2-2.1) but not for patients without elevated levels of CK or CK-MB. CONCLUSIONS: The prognostic value of cardiac troponin, beyond that supplied by CK status or important baseline characteristics, assists in the identification of patients with ACS who are at increased risk for death.

Aged↗
PubMed2006

Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with heart failure.

Enhanced iNOS (inducible nitric oxide synthase) activity may contribute to vascular dysfunction in patients with heart failure. In the present study, we aimed to determine whether iNOS activity contributes to the maintenance of vascular tone in patients with symptomatic heart failure with the use of the highly selective iNOS inhibitor 1400W {N-[3-(aminomethyl)benzyl] acetamidine}. Bilateral forearm blood flow was measured using venous occlusion plethysmography in 12 patients with New York Heart Association class II-IV heart failure and eight matched healthy control subjects during intra-brachial infusion of 1400W (0.1-1 micromol/min), L-NMMA (N(G)-monomethyl-L-arginine; a non-selective NOS inhibitor; 2-8 micromol/min) and noradrenaline (control vasoconstrictor; 60-480 pmol/min). In both patients and controls, intra-brachial infusion of L-NMMA and noradrenaline caused a dose-dependent reduction in infused forearm blood flow (P<0.05 for both): peak reduction of 32+/-6% and 37+/-4% during L-NMMA and 52+/-6% and 49+/-5% during noradrenaline respectively (P values were not significant when patients were compared with controls). In contrast, 1400W had no effect on blood flow at 1 micromol/min [-3+/-4% in patients (95% confidence intervals, -11 to 5%) and 3+/-8% in controls; P value was not significant]. In conclusion, we have demonstrated that intrabrachial selective iNOS inhibition does not influence forearm blood flow in patients with heart failure. We conclude that iNOS activity does not contribute to peripheral vascular tone in patients with symptomatic heart failure.

Aged↗
PubMed2006

High mortality rates in conservatively managed patients with acute coronary syndrome.

OBJECTIVES: The revised diagnostic criteria for the acute coronary syndrome (ACS) have created the need for accurate and representative data on treatment and outcome for the three categories of ACS. DESIGN: Consecutive patients admitted with a suspected ACS (n = 755) from February 1, 2003 to January 31, 2004 was registered and categorised into five diagnostic groups: 1) ST-elevation myocardial infarction (STEMI) (n = 126), 2) Non-ST-elevation myocardial infarction (NSTEMI) (n = 185), 3) Unstable angina pectoris (UAP) (n = 55), 4) Coronary heart disease (CHD) without ACS (n = 164) and 5) Non-coronary chest pain (n = 225). RESULTS: All-cause one-year mortality rates were 20%, 32%, 7%, 10% and 3%, in patients with STEMI, NSTEMI, UAP, CHD without ACS and non-coronary chest pain, respectively. In patients with STEMI, 61% received immediate reperfusion therapy (ratio thrombolysis: primary PCI = 18:1). Only 3% of those with NSTEMI had PCI within two days. CONCLUSION: In this conservatively managed population of consecutive patients with ACS, the one-year mortality rate is significantly higher than seen in most registries and clinical trials.

Aged↗
PubMed2006

Incidence and outcome of atrial fibrillation in stable symptomatic coronary disease.

OBJECTIVES: Evaluate the prevalence, incidence and impact on prognosis of existing and new onset atrial fibrillation (AF) in patients with stable, symptomatic coronary artery disease. DESIGN: Data from the 7 665 participants included in the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) trial was used. RESULTS: Over a mean follow-up of 4.9 years, the incidence of recurrent AF in patients with AF at baseline (4.1%) was 13.5/100 patient-years and 1.64/100 patient-years for patients without baseline AF. Patients with AF at baseline had increased mortality and new overt heart failure. New onset AF was associated with increased morbidity and mortality and in particular soon after onset. [adjusted 30-day relative risk for mortality 23, 95% CI 14-36; for debilitating stroke 37, 95% CI 18-77; and for heart failure 54, 95% CI 32-93]. The incidence of AF was not affected by treatment with nifedipine GITS. CONCLUSION: The presence of AF in patients with stable symptomatic CAD is an independent risk factor and in particular in the first 30 days for subsequent mortality and morbidity.

Aged↗
PubMed2005

Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease.

CONTEXT: Elevated concentrations of B-type natriuretic peptide (BNP) at presentation in patients with acute coronary syndrome (ACS) are associated with long-term mortality. Few data exist regarding serial assessment of BNP levels during follow-up. OBJECTIVE: To determine whether concentrations of BNP at study entry (prior to hospital discharge for ACS) and at outpatient follow-up at 4 months and 12 months are associated with subsequent clinical outcomes. DESIGN, SETTING, AND PATIENTS: Prospective observational substudy of 4497 patients with non-ST-elevation or ST-elevation ACS who were enrolled in phase Z of the A to Z trial, which was conducted in 41 countries at 322 acute care hospitals between 1999 and 2003. MAIN OUTCOME MEASURE: Death from any cause or new onset of congestive heart failure (CHF) through 2 years. RESULTS: Levels of BNP were available in 4266 patients at study entry (prior to hospital discharge), 3618 patients at 4 months, and 2966 patients at 12 months. During follow-up there were 230 deaths and 163 incident cases of CHF. Adjusting for age, sex, index event, renal function, hypertension, prior heart failure, and diabetes, elevated levels of BNP (>80 pg/mL) were associated with subsequent death or new CHF when measured at study entry (111 [21%] vs 246 [7%]; adjusted hazard ratio [HR], 2.5; 95% confidence interval [CI], 2.0-3.3), at 4 months (34 [19%] vs 125 [4%]; adjusted HR, 3.9; 95% CI, 2.6-6.0), and at 12 months (19 [11%] vs 37 [1%]; adjusted HR, 4.7; 95% CI, 2.5-8.9). Patients with newly elevated levels of BNP at 4 months were at increased risk of death or new CHF (10 [15%] vs 105 [3%]); HR, 4.5; 95% CI, 2.3-8.6). Patients with elevated levels of BNP at study entry and with BNP levels lower than 80 pg/mL at 4 months tended to have only modestly increased risk (HR, 1.7; 95% CI, 1.0-2.9) compared with patients with BNP levels lower than 80 pg/mL at both visits. CONCLUSIONS: Serial determinations of BNP levels during outpatient follow-up after ACS predict the risk of death or new CHF. Changes in BNP levels over time are associated with long-term clinical outcomes and may provide a basis for enhanced clinical decision making in patients after onset of ACS.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251576.

Coronary Disease↗
PubMed2005

Differences in the management and prognosis of women and men who suffer from acute coronary syndromes.

OBJECTIVES: The purpose of this research was to determine if sex and gender differences in the management of acute coronary syndromes (ACS) are associated with differences in prognosis after ACS. BACKGROUND: Previous investigators have reported sex/gender differences in the management of patients with ACS, but the impact of these differences on prognosis is unclear. METHODS: We analyzed data from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which enrolled 4,836 women and 7,726 men with ACS. Patients were classified into risk strata using the Thrombolysis In Myocardial Infarction (TIMI) score. RESULTS: Women underwent fewer invasive procedures including angiography, angioplasty, and coronary artery bypass graft (CABG) surgery (47.6% vs. 60.5%; p = 0.0001) compared to men. No significant differences in cardiovascular death, myocardial infarction (MI), or stroke were observed (9.8% vs. 10.9%; p = 0.04), although women were more likely than men to develop refractory ischemia and to be rehospitalized for chest pain during follow-up (16.6% vs. 13.9%; p = 0.0001). These differences were particularly evident among TIMI high-risk women. A significant interaction between TIMI risk and gender for the outcome of refractory angina and rehospitalization for angina was present. CONCLUSIONS: Compared to men, high-risk women with ACS undergo less coronary angiography, angioplasty, and CABG surgery, and while they do not have higher incidence cardiovascular death, recurrent MI, or stroke, they suffer an increased rate of refractory ischemia and rehospitalization. All high-risk women and men with ACS should receive optimal medical management, and be considered for coronary angiography with possible revascularization if their coronary anatomy warrants it.

Acute Disease↗
PubMed2005

Risk score for predicting death, myocardial infarction, and stroke in patients with stable angina, based on a large randomised trial cohort of patients.

OBJECTIVE: To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function. DESIGN: Multivariate Cox regression analysis of data from a large multicentre trial. SETTING: Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand. PARTICIPANTS: 7311 patients with all required data available. MAIN OUTCOME MEASURE: Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years. RESULTS: 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure > or = 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients. CONCLUSION: This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.

Adult↗
PubMed2005

Treating patients with acute coronary syndromes with aggressive antiplatelet therapy (from the Global Registry of Acute Coronary Events).

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.

Aged↗