Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A subgroup analysis of the VALIDATE-SWEDEHEART trial.

AIMS: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients. METHODS: This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days. RESULTS: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54-1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94-1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54-1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93-1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women. CONCLUSION: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial.

BACKGROUND: Major adverse cardiac events (MACEs) are a common cause of death after non-cardiac surgery. Despite evidence for the benefit of aspirin for secondary prevention, it is often discontinued in the perioperative period due to the risk of bleeding. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in order to compare the effect of low-dose aspirin with that of placebo on myocardial damage, cardiovascular, and bleeding complications in high-risk patients undergoing non-cardiac surgery. Aspirin (75 mg) or placebo was given 7 days before surgery and continued until the third postoperative day. Patients were followed up for 30 days after surgery. RESULTS: A total of 220 patients were enrolled, 109 patients received aspirin and 111 received placebo. Four patients (3.7%) in the aspirin group and 10 patients (9.0%) in the placebo group had elevated troponin T levels in the postoperative period (P=0.10). Twelve patients (5.4%) had an MACE during the first 30 postoperative days. Two of these patients (1.8%) were in the aspirin group and 10 patients (9.0%) were in the placebo group (P=0.02). Treatment with aspirin resulted in a 7.2% absolute risk reduction [95% confidence interval (CI), 1.3-13%] for postoperative MACE. The relative risk reduction was 80% (95% CI, 9.2-95%). Numbers needed to treat were 14 (95% CI, 7.6-78). No significant differences in bleeding complications were seen between the two groups. CONCLUSIONS: In high-risk patients undergoing non-cardiac surgery, perioperative aspirin reduced the risk of MACE without increasing bleeding complications. However, the study was not powered to evaluate bleeding complications.

Predictors of cardiac events in high-risk patients undergoing emergency surgery.

BACKGROUND: The aim of this study was to determine the incidence of myocardial damage and left ventricular myocardial dysfunction and their influence on outcome in high-risk patients undergoing non-elective surgery. METHODS: In this prospective observational study, 211 patients with American Society of Anesthesiologists classification III or IV undergoing emergent or urgent surgery were included. Troponin I (TnI) was measured pre-operatively, 12 and 48 h post-operatively. Pre-operative N-terminal fragment of B-type natriuretic peptide (NT-proBNP), as a marker for left ventricular systolic dysfunction, was analyzed. The diagnostic thresholds were set to TnI >0.06 microg/l and NT-proBNP >1800 pg/ml, respectively. Post-operative major adverse cardiac events (MACE), 30-day and 3-months mortality were recorded. RESULTS: Elevated TnI levels were detected in 33% of the patients post-operatively. A TnI elevation increased the risk of MACE (35% vs. 3% in patients with normal TnI levels, P<0.001) and 30-day mortality (23% vs. 7%, P=0.003). Increased concentrations of NT-proBNP were seen in 59% of the patients. Elevated NT-proBNP was an independent predictor of myocardial damage post-operatively, odds ratio, 6.2 [95% confidence interval (CI) 2.1-18.0] and resulted in an increased risk of MACE (21% vs. 2.5% in patients with NT-proBNP < or = 1800 pg/ml, P<0.001). CONCLUSION: Myocardial damage is common in a high-risk population undergoing unscheduled surgery. These results suggest a close correlation between myocardial damage in the post-operative period and increased concentration of NT-proBNP before surgery. The combinations of TnI and NT-proBNP are reliable markers for monitoring patients at risk in the peri-operative period as well as useful tools in our risk assessment pre-operatively in emergency surgery.

FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease.

OBJECTIVE: To develop a scoring system for risk stratification and evaluation of the effect of an early invasive strategy for treatment of unstable coronary artery disease (CAD). DESIGN: Retrospective analysis of a randomised study (FRISC II; fast revascularisation in instability in coronary disease). SETTING: 58 Scandinavian hospitals. PATIENTS: 2457 patients with unstable CAD from the FRISC II study. MAIN OUTCOME MEASURES: One year rates of mortality and death/myocardial infarction (MI). METHODS: Patients were randomly assigned to an early invasive or a non-invasive strategy. From the non-invasive cohort independent variables of death or death/MI were identified. RESULTS: Seven factors, age > 70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein), were associated with an independent increased risk for death or death/MI. In patients with > or = 5 of these factors the invasive strategy reduced mortality from 15.4% (20 of 130) to 5.2% (7 of 134) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.15 to 0.78, p = 0.006). Death/MI was also reduced in patients with 3-4 factors from 15.7% (80 of 511) to 10.8% (58 of 538) (RR 0.69, 95% CI 0.50 to 0.94, p = 0.02). Neither death nor death/MI was reduced in patients with 0-2 risk factors. CONCLUSION: In unstable CAD, this scoring system based on factors independently associated with an adverse outcome can be used shortly after admission to the hospital for risk stratification and for selection of patients to an early invasive treatment strategy.

Troponin T-values provide long-term prognosis in elderly patients undergoing non-cardiac surgery.

BACKGROUND: The aim of this study was to evaluate the significance of elevated postoperative Troponin T (TnT) levels in an elderly population undergoing non-cardiac surgery. METHODS: Five hundred and forty-six consecutive patients aged 70 years or older undergoing non-cardiac surgery of >30-min duration were enrolled in this prospective, observational study. A postoperative TnT measurement was obtained on the 5th to 7th postoperative day. Troponin T values greater than 0.02 ng ml(-1) were considered positive. Patients were followed over a 1-year period, and mortality and non-fatal cardiac events (acute myocardial infarction and coronary interventions) were recorded. RESULTS: Troponin T concentrations greater than 0.02 ng ml(-1) were detected in 53 of the study subjects (9.7%). Eleven per cent of the patients with elevated TnT had electrocardiographic or clinical signs of myocardial ischemia. One year after surgery, 17 (32%) of the patients with abnormal TnT concentrations had died. In a multivariate Cox regression analysis adjusting for baseline and perioperative data, a TnT value >0.02 ng ml(-1) was an independent correlate of the mortality adjusted hazard ratio (HR): 14.9 (95% CI 3.7-60.3). Other independent predictors of death were tachycardia (HR, 14.9 95% CI 3.45-64.8), ASA 4 (HR, 8.1 95% CI 1.3-50.0), reoperation (HR, 6.4 95% CI 1.1-36.9), and use of diuretics (HR, 4.2 95% CI 1.3-13.8). CONCLUSION: We conclude that elevated TnT levels in the postoperative period confer a 15-fold increase in mortality during the first year after surgery. Our findings also provide evidence that silent myocardial ischemia is common in an elderly population. Routine perioperative surveillance for TnT might therefore be of use in detecting patients at an increased risk of mortality during the first postoperative year.

Cost effectiveness of extended treatment with low molecular weight heparin (dalteparin) in unstable coronary artery disease: results from the FRISC II trial.

BACKGROUND: In unstable coronary artery disease short term treatment with low molecular weight heparin in addition to aspirin has been shown to be effective. OBJECTIVE: To assess the cost effectiveness of extended treatment with dalteparin in patients managed with a non-invasive treatment strategy. DESIGN: Prospective, randomised, multicentre study. SETTING: 58 centres in Sweden, Denmark, and Norway, of which 16 were interventional. PATIENTS: After at least five days' treatment with open label dalteparin, 2267 patients were randomised to continue double blind treatment with either subcutaneous dalteparin twice daily or placebo for three months. The patients' use of health service resources was recorded prospectively. MAIN OUTCOME MEASURE: Death/myocardial infarction. RESULTS: After one month into the double blind period there was a 47% relative reduction in death or myocardial infarction in the dalteparin group compared with the placebo group (p = 0.002). There was a non-significant mean cost difference, favouring the placebo group, of 849 Swedish crowns (SEK) per patient (equivalent to 58 pounds sterling). The incremental cost effectiveness ratio for giving dalteparin treatment for one month was SEK 30 300 (range -78 000 to 139 000) (2060 pounds sterling, range -5300 pounds sterling to pound 9400 pounds sterling) per avoided death or myocardial infarct. At three months, the decrease in death or myocardial infarction was not significant, precluding cost effectiveness analyses. CONCLUSIONS: There is a marginal and non-significant increase in costs for one month of extended dalteparin treatment compared with placebo. Extended dalteparin treatment lowers the risk of death or myocardial infarction in patients with unstable coronary artery disease. While in many countries the resources for early intervention are limited, extended dalteparin treatment up to one month is a cost effective bridge to invasive intervention.

Benefits of extended treatment with dalteparin in patients with unstable coronary artery disease eligible for revascularization.

AIMS: The FRISC II trial demonstrated that, for patients with unstable coronary artery disease, an early invasive strategy following acute treatment with dalteparin and aspirin, was superior to a more conservative approach. We evaluated whether it is beneficial to extend treatment with dalteparin to patients eligible for revascularization but for whom these procedures are performed after the initial hospital stay. METHODS AND RESULTS: As a subanalysis of FRISC II, the efficacy and clinical safety of extended dalteparin treatment (5000 or 7500 IU.12h(-1) to day 90) compared with placebo was assessed in 1601 patients randomized to a non-invasive group who underwent revascularization only when necessary because of recurring symptoms, (re)infarction, or severe ischaemia. By day 90, 440 patients had undergone revascularization: 267 of these procedures occurred during the double-blind period. All patients initially received acute treatment (5-7 days from day 1) with dalteparin (120 IU/kg(-1) 12h(-1)). The incidence of death and/or myocardial infarction was monitored until revascularization or day 45 and until revascularization or day 90. There was a significant difference in the estimated probability of death and/or myocardial infarction until revascularization or day 90 in favour of dalteparin (log-rank test, P=0.0415) and there was a significant reduction in death and/or myocardial infarction in favour of extended dalteparin treatment at day 45, with a 57% relative risk reduction (P=0.0004). At day 90 the relative risk reduction was 29%. The safety profile of extended dalteparin treatment was similar to that of acute usage. CONCLUSION: Extended dalteparin treatment for up to 45 days is effective and safe as a bridging therapy for patients with unstable coronary artery disease awaiting revascularization.

Cost-effectiveness of an invasive strategy in unstable coronary artery disease; results from the FRISC II invasive trial. The Fast Revascularisation during InStability in Coronary artery disease.

AIMS: The utilization and timing of revascularization in unstable coronary artery disease varies, which could have important consequences for patients and for treatment costs. The FRISC II invasive trial compared an early invasive strategy vs a non-invasive strategy with respect to the composite end-point of death and myocardial infarction as well as costs. METHODS AND RESULTS: A total of 2457 patients, median age 66 years, comprising 70% men, were randomized. We prospectively recorded the patients' use of the health service. The results were analysed in a societal perspective. There was a significant 1.7% absolute reduction in deaths and a 3.7% absolute reduction in deaths and myocardial infarctions in the invasive compared to the non-invasive group after 12 months. During the initial hospitalization a patient in the invasive group spent on average 3.9 more days in hospital than a patient in the non-invasive group. Opposite results were found for rehospitalizations. The difference in mean total costs is SEK 23 876 (P<0.001). The incermental cost-effective ratio for choosing the invasive instead of the non-invasive strategy is SEK 1 404 000 per avoided death and SEK 645 000 per avoided death or myocardial infarction. CONCLUSION: The high cost at the beginning of the invasive strategy is substantial. The clinical results of the FRISC II study provided evidence that the invasive strategy reduces the rate of death and myocardial infarction in patients with unstable coronary artery disease. For policy discussions concerning whether or not to implement the invasive strategy, these positive results should be balanced against the cost-consequences of the strategy.

[Management of cardiovascular diseases is characterized by male perspective. Women are subjected to incorrect management, diagnosis and treatment]. / Hantering av hjärt--kärlsjukdom präglas av manligt perspektiv. Kvinnor får felaktiga omhändertaganden, diagnoser och behandlingar.

In women as well as in men cardiovascular disease is common, and almost as many women as men suffer from myocardial infarction every year in Sweden. In spite of this, studies on female cardiovascular disease are few in number. Knowledge about differences in risk factors, prevention, treatment and management is not common. Female cardiovascular disease starts approximately ten years later than in men and consequently most women are excluded from studies because of low age limits for inclusion. Primary preventive effects of e.g. acetylsalicylic acid, lipid-lowering drugs, vitamins and exercise have only been studied in healthy men, but the conclusions have been applied on women as well. The effects of reducing triglyceride levels or abdominal obesity in women--important risk factors for cardiovascular disease--have not been studied in controlled randomized studies. In women, angina is a non-specific symptom, and false positive ECG's are much more frequent than in men. The fact that a woman has to present as a man in order to be treated professionally (the Yentl syndrome) is still at hand. There is a great need for spreading current knowledge regarding gender differences among colleagues and medical students.

Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? FRISC II Study Group Investigators.

BACKGROUND: The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC II) trial compared the effectiveness of an early invasive versus a noninvasive strategy in terms of the incidence of death and myocardial infarction (MI) in patients with unstable coronary artery disease (CAD). OBJECTIVES: In this subanalysis, we sought to evaluate gender differences in the effect of these different strategies. METHODS: The patients (749 women and 1,708 men) were randomized to early invasive or noninvasive strategies. Coronary angiography was performed within the first 7 days in 96% and 10% of the invasive and noninvasive groups, respectively, and revascularization was performed within the first 10 days in 71% and 9% of the invasive and noninvasive groups, respectively. RESULTS: Women presenting with unstable CAD were older, but fewer had previous infarctions, left ventricular dysfunction and elevated troponin T levels. Women had fewer angiographic changes. There was no difference in MI or death at 12 months among women in the invasive and noninvasive groups (12.4% vs. 10.5%, respectively), in contrast to the favorable effect in the invasively treated group of men (9.6% vs. 15.8%, p < 0.001). In an interaction analysis, there was a different effect of the early invasive strategy for the two genders (p = 0.008). CONCLUSIONS: Women with symptoms and/or signs of unstable CAD are older, but still have less severe CAD and a better prognosis compared with men. In contrast to its beneficial effect in men, an early invasive strategy did not reduce the risk of future events among women. Further research is warranted to identify the most appropriate treatment strategy in women with unstable CAD.

The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study.

Rapid reperfusion of an infarct-related artery reduces the extent of myocardial damage and improves survival in acute myocardial infarction (AMI). Currently, anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH) dalteparin is at least as effective as UFH in unstable coronary artery disease. The ASSENT PLUS trial was carried out to evaluate whether dalteparin is as effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt-PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA and dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and clinical events (death, reinfarction, or revascularization) up to 30 days. There was a clear trend toward greater TIMI 3 flow with dalteparin compared with UFH. There was significantly less TIMI 0-1 flow or thrombus in the dalteparin group. Bleeding rates were similar. The occurrence of reinfarction was reduced during dalteparin treatment. These findings suggest that dalteparin could be substituted for UFH as an adjunct to rt-PA/aspirin in the management of patients with AMI.

Fibrinolytic variables in postmenopausal women with unstable coronary artery disease.

OBJECTIVES: Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients is unknown but may be due to altered fibrinolytic function enhancing thrombosis formation. We evaluated the two key components of the fibrinolytic system, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in women with clinical signs of unstable coronary artery disease (CAD). METHODS AND RESULTS: 158 patients with unstable CAD and 101 controls were examined. Of the patients 16% had normal vessels and 84% coronary atherosclerosis at coronary angiography. Mean plasma concentration of t-PA-ag, but not of PAI-1-act was higher in patients than in controls (t-PA-ag: 2.12 (2.05;2.19) vs. 1.98 (1.89;2.07), p<0.05; PAI-1-act: 1.55 (1.35;1.74) vs. 1.49 (1.24;1.73), p=n.s.). Patients with coronary atherosclerosis had significantly higher mean plasma levels of both t-PA-ag and PAI-1-act than patients with normal coronary vessels (t-PA-ag: 2.16 (2.08;2.33) vs. 1.94 (1.78;2.10), p<0.05; PAI-1-act: 1.68 (1.47;1.90) vs. 0.82 (0.43;1.21), p<0.01), and these differences were seen whether markers of myocardial damage were elevated or not. Mean plasma levels of PAI-1-act in patients with normal coronary vessels were even lower than in the control group (p<0.05). Almost all significant differences in mean plasma t-PA-ag and PAI-1-act disappeared after adjustments for known covariates. CONCLUSION: Our results indicate, regardless of myocardial marker elevation or not, an activated fibrinolytic system in postmenopausal women with unstable CAD and coronary atherosclerosis, but not in the same group of patients with normal coronary vessels. This argues against reduced fibrinolytic capacity in the latter patients and therefore against thrombosis formation as the cause of chest pain in these women. However, we cannot exclude that the differences can be an effect of inequality among some common risk factors between the groups.

Plasma total homocysteine levels in postmenopausal women with unstable coronary artery disease.

An elevated plasma total homocysteine (tHcy) level is considered a risk factor for coronary artery disease (CAD), but the relationship between plasma tHcy and well-defined CAD in women is still unclear. Plasma tHcy concentrations and the covariates serum folate, vitamin B12, and creatinine were analysed in 157 angiographically examined postmenopausal women with unstable CAD and in 101 healthy controls. At coronary angiography, 16% had normal vessels and 84% had coronary atherosclerosis. Mean plasma tHcy concentration (micromol/l, 95% confidence interval) did not differ in patients compared to controls (13.1 (12.3-13.8) vs. 12.5 (11.6-13.5)) or in patients with or without coronary atherosclerosis (13.3 (12.4-14.1) vs. 12.0 (10.8-13.2)). A trend to an increasing plasma tHcy with increasing degree of coronary atherosclerosis was attenuated after adjustment for age and the previous mentioned covariates. Odds ratio for the risk of coronary artery disease and coronary atherosclerosis in hyperhomocysteinemic patients (> or =90th percentile in controls) was approximately 3. However, the confidence interval included unity in half of the groups and the significance was therefore difficult to judge. Receiver operating characteristics showed age to be the only variable with a significant discriminatory ability regarding the presence of coronary atherosclerosis (area 0.77). Mild hyperhomocysteinemia seems not to be related to the risk of unstable CAD in postmenopausal women. The trend towards higher plasma tHcy with increasing degree of coronary atherosclerosis may be a marker of the disease. In future studies adjustment for age and the other three covariates should be considered.

Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics.

OBJECTIVES: Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenicity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD). METHODS AND RESULTS: A total of 158 patients with unstable CAD and 101 controls were examined: 16% of the patients had normal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor antigen, soluble fibrin (SF), thrombin-antithrombin complex and D-dimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1+2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared with those with normal coronary vessels, although only significantly higher for SF. D-Dimer was significantly higher in patients with normal coronary vessels compared with the control group. Although multivariate analyses showed strong significant correlations of the haemostatic variables to the diagnosis of unstable CAD, receiver operating characteristics (ROC) revealed that none of the variables represented high diagnostic accuracy in separating patients with unstable CAD. Likewise, none of the variables was particularly good at identifying coronary atherosclerosis. CONCLUSION: Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, whereas this does not seem to be the case in patients with normal vessels. ROC revealed no variable to be particularly clinically useful in separating patients from controls or patients from those without coronary atherosclerosis.

Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease.

BACKGROUND: The Fragmin and Fast Revascularisation during Instability in Coronary artery disease II trial (FRISC II) compared an early invasive with an early non-invasive strategy in unstable coronary-artery disease. We report outcome at 1 year. METHODS: 2457 patients were randomly assigned invasive or non-invasive treatment and 3 months of dalteparin or placebo. Complete information at 1 year was available for 1222 in the invasive group and 1234 in the non-invasive group. Analyses were by intention to treat. FINDINGS: Revascularisation was done within the first 10 days in 71% of the invasive group and 9% of the non-invasive group and within the first year in 78% and 43%. During the first year, 27 (2.2%) patients in the invasive group and 48 (3.9%) in the non-invasive group died (risk ratio 0.57 [95% CI 0.36-0.90], p=0.016). 105 (8.6%) versus 143 (11.6%) had myocardial infarction (0.74 [0.59-0.94], p=0.015). The composite of death or myocardial infarction occurred in 127 (10.4%) versus 174 (14.1%) patients (0.74 [0.60-0.92], p=0.005). There were also reductions in readmission (451 [37%] vs 704 [57%]; 0.67 [0.62-0.72]), and revascularisation after the initial admission (92 [7.5%] vs 383 [31%]; 0.24 [0.20-0.30]). The results did not interact with the dalteparin/placebo allocation. INTERPRETATION: After 1 year in 100 patients, an invasive strategy saves 1.7 lives, prevents 2.0 non-fatal myocardial infarctions and 20 readmissions, and provides earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischaemia on electrocardiography or raised levels of biochemical markers of myocardial damage.

Risk stratification in unstable coronary artery disease--exercise test and troponin T from a gender perspective. FRISC-Study Group. Fragmin during InStability in Coronary artery disease.

OBJECTIVES: The study was done to determine the prognostic yield of an early symptom-limited exercise test (ET) and measurement of troponin T (TnT) in men and women with unstable coronary artery disease (CAD), with special reference to gender differences. BACKGROUND: Early risk assessment is essential for the application of appropriate treatment and further management in patients with unstable CAD. The early symptom-limited ET together with specific biochemical marker determination is an inexpensive, widely applicable method for early risk stratification. In women, however, the ET is considered less reliable, and there are few data on biochemical markers for risk stratification in women. METHODS: In a substudy of the Fragmin during InStability in Coronary artery disease (FRISC I) trial, 395 women and 778 men with unstable CAD who performed an early ET were followed for six months. Blood samples for TnT determination were taken in 342 women and 621 men at inclusion. RESULTS: Based on the ET results, low-, intermediate-, and high-risk response groups were identified with event rates of cardiac death or myocardial infarction (MI) of 1%, 9%, and 19%, respectively, among women and 8%, 14%, and 20%, respectively, among men. Patients who could not perform the ET had an event rate similar to the high-risk group. The TnT levels were divided into three groups: <0.06, 0.06-0.19, and > or = 0.20 microg/liter with event rates of 1%, 10%, and 18%, respectively, among women and 9%, 14%, and 18%, respectively, among men. Combining the ET results with TnT levels identified a low-risk group with an event rate of 3% in the male population and no events in the female population. CONCLUSIONS: Direct comparison between men and women from the same population with a high pretest likelihood of disease suggests that both TnT and the early symptom-limited ET are at least as useful as prognostic risk indicators in women as they are in men.

Plasma lipoprotein particle concentrations in postmenopausal women with unstable coronary artery disease. Analysis of diagnostic accuracy using receiver operating characteristics.

BACKGROUND: The contribution of plasma lipids to cardiovascular risk is usually evaluated by measuring plasma concentrations of total cholesterol, triglycerides and HDL cholesterol, and calculating LDL cholesterol concentration. We investigated plasma concentrations of apolipoproteins and lipoprotein particles in women with unstable coronary artery disease (CAD) to evaluate whether these, better than the routine lipid status, could differentiate women with and without coronary atherosclerosis. METHODS: Blood samples for lipid analyses were collected from 119 angiographically examined postmenopausal 49-79-year-old women with unstable CAD, and from 101 age-matched controls. Mean plasma concentrations were compared and the discriminatory ability of the different variables were tested using receiver operating characteristics (ROC). RESULTS: At coronary angiography 19% had normal vessels and 81% had coronary atherosclerosis. A disturbed triglyceride metabolism was the most pronounced lipid abnormality in women with unstable CAD and coronary atherosclerosis. ROC showed that none of the evaluated variables had a particularly high discriminatory power regarding unstable CAD or coronary atherosclerosis. The ratio cholesterol/HDL cholesterol was best with an ROC area of 0.79. Furthermore, the newer lipid variables, i.e. lipoprotein particles and apolipoproteins, were no better than the traditional variables. CONCLUSION: Lipoprotein changes reflecting a disturbed triglyceride metabolism are most pronounced in women with unstable CAD and coronary atherosclerosis. Lipoprotein particles and apolipoproteins alone were no better than lipids and lipoproteins in separating women with from those without coronary atherosclerosis. Our study does not support the measurement of apolipoproteins and lipoprotein particles on the basis of diagnostic accuracy alone.