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L Wallentin

Publications and source records attributed to L Wallentin.

At least 73 records · Page 4Linked to original sources
PubMed1999

Low-molecular-weight heparins in coronary thrombosis: today and tomorrow.

Data from several large-scale studies have suggested that low-molecular-weight heparin (LMWH) may be superior to standard heparin therapy in the setting of unstable coronary syndromes. Studies looking at the optimal duration of treatment have produced conflicting results; however, data from a recent large trial suggest that prolongation of treatment is associated with a significant benefit. The recommended initial treatment for patients with unstable coronary syndromes is a combination of LMWH and aspirin. Stablilized patients at moderate or high risk - such as those with ST-segment depression or increased troponin levels - should continue with this treatment until they have undergone coronary angiography and, if appropriate, an invasive procedure. In a recent small study among patients with acute myocardial infarction, the use of LMWH as an adjunct to streptokinase produced significant therapeutic benefits. Other potential uses for LMWH include a role in angioplasty.

Anticoagulants↗
PubMed1998

Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: a double-blind, randomized angiographic trial of lanoteplase versus alteplase.

BACKGROUND: Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS: InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.

Adolescent↗
PubMed1998

[Early management of unstable coronary artery disease. Coronary angiography is the first measure in high-risk patients].

Unstable coronary artery disease is currently the major cause of admissions to coronary intensive care units, accounting for 30-40 per cent of cases. The underlying cause is rupture of an atherosclerotic plaque, coronary blood flow being impeded by a superimposed thrombus. New and more effective antithrombotic drugs are becoming increasingly available. Simultaneous early coronary angioplasty, stenting or bypass surgery provide the most effective amelioration of symptoms. Early revascularisation has not hitherto been found to reduce the risk of myocardial infarction or mortality in patients without signs of severe ischaemia. In this large category of cardiac patients, treatment strategy selection is of considerable importance to the effective utilisation of resources.

Angioplasty, Balloon, Coronary↗
PubMed1998

[Emergency coronary care--successful, but unequaly distributed].

The need of acute coronary care is increasing because of an increase in the incidence of severe angina pectoris, and despite a reduction in that of acute myocardial infarction. Patients with acute myocardial infarction are characterised by continuously increasing age, lower mortality, and shorter hospitalisation. The improvement in acute care is related to increased use of expensive drugs, new diagnostic methods, and an increasing coronary revascularisation rate. However, there is still inequality in the utilisation of cardiac care, and in order to further enhance its quality and equality of utilisation, there is an emphatic need of common registries.

Acute Disease↗
PubMed1998

[Uniform diagnosis of myocardial infarction. Rapid development at Swedish hospitals].

Criteria for the diagnosis of myocardial infarction vary not only from one cardiac intensive care unit (CICU) to another, but also from one study to another. Even the appropriate juncture for ECG, the type of biochemical markers used and blood sampling times vary. Thus, epidemiological studies comparing results over time or between various regions or hospitals tend to be misleading. Reported results are difficult to interpret and to apply to one's own CICU. In order to survey myocardial infarction diagnosis in Sweden and planned future changes, in February-March 1997 a questionnaire was sent to all 82 CICUs in the country. Of the 74 (90%) responders, 72% (53/74) reported formalized printed criteria for myocardial diagnosis to be available at the unit. Eight different biochemical markers of myocardial injury were in use; CK-MB (creatine kinase and its cardio-specific isoenzyme) was the most common, being used at 64% (47/74) of the units; CK and CK-B were used at 32%, and troponin T or I at 53%. Myoglobulin has not been very widely used. If planned changes are carried out, 86% of the units will soon be using CK-MB, and 79% troponin T och I. Cut-off levels of biochemical markers of myocardial infarction varied. Of the 47 units where CK-MB was used, the cut-off level was 10 micrograms/L at 10 (28%) of the units, 15 micrograms/L at 31 (66%) units, and a higher level in a smaller group of units. Cut-off levels for CK-B manifested a similar lack of uniformity. The greatest difference was manifested by troponin levels; of the 28 units using quantitative tests and that cited their cut-off levels, three (11%) used 0.10 microgram/L, 12 (43%) used 0.20 microgram/L, and the remaining 13 (46%) used 0.50 microgram/L. The use of ischaemia monitoring in conjunction with diagnosis and prognosis of myocardial infarction has increased, 72% of the units reporting that they used some form of monitoring, and a further 13% that they planned to introduce it in the near future. Thus, the questionnaire study showed marked differences in myocardial infarction diagnosis to exist in Sweden, although a manifest trend toward increasing uniformity was also seen, and the outlook for the standardisation of diagnostic criteria is good.

Biomarkers↗
PubMed1998

Management strategies for a better outcome in unstable coronary artery disease.

Unstable coronary artery disease is a term encompassing both unstable angina and non-Q-wave (non-ST-segment elevation) myocardial infarction. Patients with these conditions are at risk of early progression to acute myocardial infarction and death. Thus, management of these conditions must aim to reduce long-term mortality and morbidity. Risk stratification is crucial for the identification of patients whose risk of early progression is high; they may require coronary angiography and (if suitable) either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. No single variable can accurately predict risk, but considerable data are emerging to show that biochemical markers of myocardial injury, such as troponin-T and troponin-I, are valuable in combination with electrocardiographic findings and clinical features. Routine early invasive procedures (coronary angiography with or without revascularization) have not yet been shown to have any significant advantage over conservative regimens for the majority of patients. Antiplatelet, anticoagulant, and anti-ischemic agents remain the mainstay of treatment in the acute phase. New agents, such as glycoprotein IIb/IIIa receptor inhibitors and low-molecular-weight heparins, as well as antithrombins and Factor Xa inhibitors add to the treatments currently available. Thrombolytic agents are contraindicated in the absence of ST-segment elevation. After clinical stabilization, ongoing assessment should include exercise testing for all patients who are able; other imaging techniques should be used for patients unable to exercise. A profile indicating a high risk of future events is an indication for elective angiography and consideration for revascularization.

Algorithms↗
PubMed1998

No Prognostic Importance of Resistance to Activated Protein C in Unstable Coronary Artery Disease Despite Signs of Thrombin Activation.

Resistance to activated protein C (APC resistance) is the single most important hemostatic defect associated with venous thromboembolic disease. However, little is. Known about this defect in arterial disease. The aim of this study was thus to investigate the frequency and prognostic importance of APC resistance and its influence on the coagulation system in one type of arterial thrombosis. In this study, 323 patients admitted to hospital because of unstable coronary artery disease, that is, unstable angina pectoris or non-Q-wave myocardial infarction, were investigated and compared with a reference group of apparently healthy individuals. The patients participated in a prospective, multicenter, randomized, and placebo-controlled investigation evaluating the protective value of low molecular weight heparin (dalteparin) in unstable coronary artery disease. The APC ratio was assayed using a modified activated partial thromboplastin time reaction method to measure the response to activated protein C. APC resistance was defined as an APC ratio </=2.2. Signs of thrombin activation were measured by prothrombin fragment 1+2 levels. The 7.2% (23/318) occurrence of APC resistance found in patients did not differ from the 5.8% (4/69) level in the reference population (P = 0.16). A significant elevation of the prothrombin fragment 1+2 median level of 2.5 nM (interquartile range, 1.9-3.2 nM) was found in the patients with APC resistance compared with 1.7 nM (interquartile range, 1.2-2.4nM) in the group with a normal APC ratio (P < 0.01). During the 150-day follow-up period, there was no increased risk of cardiac events in patients with APC resistance. Although accompanied by signs of increased thrombin formation, APC resistance doesnot seem to be an important risk factor for the development of instability in coronary artery disease.

Journal Article↗
PubMed1998

Increased fibrinogen levels are associated with persistent Chlamydia pneumoniae infection in unstable coronary artery disease.

AIM: Increased levels of acute phase proteins, e.g., fibrinogen, are related to a poor outcome in unstable coronary artery disease, but the cause of inflammation is unknown. We therefore investigated the prevalence of persistent Chlamydia pneumoniae infection, and its relationship to inflammation in this condition. METHODS AND RESULTS: In 256 patients participating in the FRISC trial, evaluating the effects of dalteparin (a low molecular weight heparin) in unstable angina or non-Q wave myocardial infarction, Chlamydia pneumoniae IgA antibody titres and levels of fibrinogen, C-reactive protein and troponin T were determined at inclusion. Increased C. pneumoniae IgA antibody titres were significantly more common in the patients (36%) than in a reference population of similar age (19%); P < 0.001. Raised titres were associated with male gender, increasing age, smoking, and elevated concentrations of fibrinogen, C-reactive protein and troponin T. The association between persistent C. pneumoniae infection and increased fibrinogen levels was independent of other risk factors evaluated in multivariate analysis (P = 0.009). CONCLUSION: Persistent C. pneumoniae infection is common in unstable coronary artery disease. The independent association between increased C. pneumoniae IgA antibody titres and fibrinogen levels indicates that chronic infection could be of importance for disease activity.

Angina, Unstable↗
PubMed1998

Low-molecular weight heparin reduces the generation and activity of thrombin in unstable coronary artery disease.

Unstable coronary artery disease (UCAD) is associated with an increased risk of further coronary events. In the FRISC study, the risk was decreased during treatment with a high, twice-daily, dose of dalteparin, a low-molecular-weight heparin. However, lowering the dose resulted in raised risk of recurrences. To investigate the underlying pathophysiology, the thrombin generation and activity in patients with UCAD randomized to a 6-week placebo-controlled treatment with dalteparin were evaluated. Plasma prothrombin fragment 1+2 (F1+2) (n = 342), thrombin-antithrombin complex (TAT) (n = 186) and soluble fibrin (SF) (n = 298) were analyzed before and during treatment with dalteparin/placebo administered subcutaneously, 120 IU/kg bw twice daily for 5-8 days and 7.500 IU once daily the following 35-40 days. High-dose treatment with dalteparin resulted in significantly reduced levels of all coagulation markers, demonstrating diminished thrombin generation and activity. When reducing the dalteparin dose, plasma TAT and SF remained low, indicating minimal fibrin formation. However, F1+2 increased during this period. though the level at day 45 was still lower than in the placebo group. In the placebo group elevated thrombin generation and activity persisted during the entire period. In conclusion, high-dose treatment with dalteparin twice daily resulted in significantly reduced thrombin generation and activity. However, after changing to a lower, once-daily dose, the treatment was not sufficient in preventing a return to a procoagulable state. These changes of the coagulation activity might explain the changes in event rate observed during dalteparin treatment.

Aged↗
PubMed1998

The FRISC experience with troponin T. Use as decision tool and comparison with other prognostic markers.

Early prognostic evaluation is essential for the application of appropriate treatment and further management in the heterogeneous population with unstable coronary artery disease. Among the variety of prognostic indicators that have been suggested, biochemical markers of myocardial damage, especially the troponins, have gained increasing interest. The FRISC troponin T (TnT) substudy has validated and provided additional insights into the use of biochemical markers for prognostic evaluation. Nine hundred and seventy-eight patients were enrolled and followed for 5 months. An increase in the rate of cardiac death or myocardial infarction was seen during follow-up, with increasing levels of TnT. The TnT level separated low and high risk patients better than the conventional division of unstable angina and myocardial infarction. In the comparison with other early available risk indicators TnT was an independent risk indicator and gave additive prognostic information to both inclusion ECG and the result of a predischarge exercise test. TnT was superior to CK-MB for risk stratification, while TnT and troponin I showed comparable results. In patients with elevated TnT, treatment with dalteparin significantly decreased the risk for death or myocardial infarction compared to placebo, while there was no benefit from dalteparin in patients without Tn-T elevation. Based on the experiences of the FRISC study and the literature we suggest that the use of troponins should be included in the diagnostic and prognostic evaluation of patients with suspicion of unstable coronary artery disease.

Aged↗
PubMed1997

Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease.

BACKGROUND: The prognostic influences of fibrinogen and C-reactive protein levels and their relations to myocardial damage in unstable coronary artery syndromes have not been well described. METHODS AND RESULTS: Fibrinogen and C-reactive protein were determined at inclusion and related to outcome after 5 months in 965 patients with unstable angina or non-Q-wave myocardial infarction randomized to 5 weeks with low-molecular-weight heparin or placebo. The probabilities of death were 1.6%, 4.6%, and 6.9% (P=.005) and the probabilities of death and/or myocardial infarction were 9.3%, 14.2%, and 19.1% (P=.002), respectively, in patients stratified by tertiles of fibrinogen (< 3.38, 3.38 to 3.99, and > or = 4.0 g/L). The probabilities of death were 2.2%, 3.6%, and 7.5% (P=.003) after stratification of patient data by tertiles of C-reactive protein level (< 2, 2 to 10, and > 10 mg/L). In logistic multiple regression analysis, increased fibrinogen levels were independently associated with the incidence of death and/or myocardial infarction (P=.013), and elevated C-reactive protein level was associated with the incidence of death (P=.012). The increased relative risk of subsequent death or myocardial infarction in individuals with an elevated fibrinogen level was consistent in most subgroups evaluated; although significantly so only in patients with signs of myocardial damage. CONCLUSIONS: Increased levels of both fibrinogen and C-reactive protein are associated with a worse outcome in patients with unstable coronary artery disease. The increased risk associated with elevated fibrinogen levels is independent of, and additive to, the prognostic influence of myocardial damage.

Aged↗
PubMed1997

Low-molecular-weight heparin (Fragmin) during instability in coronary artery disease (FRISC). FRISC Study Group.

This study evaluated whether the low-molecular-weight (LMW) heparin dalteparin sodium (Fragmin) had protective effects against cardiac events in aspirin-treated patients with unstable coronary artery syndromes. Patients (n = 1,506) with unstable angina or non-Q-wave myocardial infarction were randomized to double-blind, placebo-controlled treatment with LMW heparin. The treatment was given as subcutaneous injections: 120 U/kg body weight/12 hours during the first 5-7 days and 7,500 U once daily during the following 35-45 days. The primary endpoint, death or myocardial infarction after 6 days, showed a 3% (4.7%-1.7%) absolute and a 65% relative reduction in the LMW heparin group. There was a 6.8% (15.5%-8.7%) absolute and a 47% relative reduction of urgent revascularization or need for heparin or nitroglycerin infusions in combination with the primary endpoint. After 40 days there was an absolute reduction of death or myocardial infarction of 2.8% (10.7%-7.9%) and its combination with incapacitating angina was reduced by 5.9% (30.7%-24.8%). The survival analysis indicated a reactivation of the instability soon after lowering the dose at 5-7 days. With long-term follow-up, 3-4 months after termination of LMW heparin, the differences between groups were no longer statistically significant. However, the cumulative reduction in death, myocardial infarction, and revascularization because of incapacitating angina of 5.1% (25.3%-20.4%) was maintained. No cerebral and few major bleeds occurred. Compliance was adequate. Thus, subcutaneous LMW heparin protects against cardiac events in the acute phase of unstable coronary artery disease. The subcutaneous regimen also allows prolongation of treatment in the outpatient setting, which might maintain the initial benefits over a longer period.

Adult↗
PubMed1997

Noninvasive risk stratification in unstable coronary artery disease: exercise test and biochemical markers. FRISC Study Group.

Early risk assessment is essential for the application of appropriate treatment and further management in patients with unstable coronary artery disease, i.e., unstable angina or non-Q-wave myocardial infarction. In this article, the use of exercise testing and biochemical markers for identification of high- and low-risk patients is discussed, with special reference to experiences from the FRISC (Fragmin During Instability in Coronary Artery Disease) trial. It is concluded that a symptom-limited predischarge exercise test (provided all relevant information obtained is considered) and determination of troponin T are inexpensive, widely applicable, and useful methods for early risk stratification in both men and women after an episode of unstable coronary artery disease.

Biomarkers↗
PubMed1997

Long-term low-molecular-weight heparin (Fragmin) and/or early revascularization during instability in coronary artery disease (the FRISC II Study).

The Fragmin and/or Early Revascularisation during Instability in Coronary Artery Disease (FRISC II) trial will, in a prospective multicenter factorially randomized study, compare the efficacy of 3 months continuation of subcutaneous treatment with the low-molecular-weight heparin dalteparin (Fragmin) with that of placebo and will also compare a direct invasive strategy with a stepwise selective approach with regard to the utilization of coronary angiography and revascularization in patients with unstable coronary artery disease. The primary endpoints are death or myocardial infarction after 3 and 6 months respectively. Secondary endpoints are the same events after 12-24 months and also cardiac symptoms, exercise capacity, and/or signs of myocardial ischemia, readmission, and costs. Analyses will also be made of subgroups based on inclusion diagnosis, initial elevation of biochemical markers of myocardial damage, elevation of fibrinogen or C-reactive protein, signs of ischemia in electrocardiography at rest or at continuous 24-hour ischemia monitoring, and left ventricular function at echocardiography. Altogether, 3,100 patients will be recruited in 65-70 Scandinavian centers. Completion of follow-up is anticipated in the second half of 1998. The FRISC II study will further elucidate new alternatives for antithrombotic, invasive, and individually tailored treatment of unstable coronary syndromes.

Angina, Unstable↗
PubMed1997

Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group.

OBJECTIVES: We sought to evaluate whether troponin T might be used for identification of patients with unstable coronary artery disease in whom treatment with low molecular weight heparin is beneficial. BACKGROUND: Early identification of subgroups with differences in response to a certain treatment is important to optimize the utilization of different therapeutic approaches. METHODS: Nine-hundred seventy-one patients with unstable coronary artery disease who participated in a trial of the low molecular weight heparin dalteparin (Fragmin) and who provided blood samples were classified into subgroups according to troponin T level. In the short-term phase all patients received subcutaneous dalteparin/placebo twice daily for 6 days. During the long-term phase they continued with daltparin/placebo once daily for another 5 weeks. RESULTS: In the short-term phase, dalteparin reduced the incidence of death or myocardial infarction from 2.4% to 0% (p = 0.12) and from 6.0% to 2.5% (p < 0.05) in 327 and 644 patients with troponin T levels < 0.1 and > or = 0.1 micrograms/liter, respectively. During long-term treatment there was an increasing difference between the placebo and dalteparin group in those with troponin T levels > or = 0.1 microgram/liter, in whom the incidences at 40 days were 14.2% and 7.4%, respectively (p < 0.01). In contrast, no beneficial effect of the long-term treatment could be demonstrated in those with troponin T levels < 0.1 microgram/liter (4.7% vs. 5.7%). CONCLUSIONS: Elevation of troponin T identifies a subgroup of patients in whom prolonged antithrombotic treatment (e.g., with dalteparin) is beneficial.

Aged↗
PubMed1997

Risk stratification in unstable coronary artery disease. Additive value of troponin T determinations and pre-discharge exercise tests. FRISK Study Group.

In 963 patients, participating in a randomized study of low molecular weight heparin in unstable coronary artery disease and followed for 5 months, troponin T was determined. In the 766 patients with a pre-discharge exercise test both troponin T level and exercise test response were independent predictors of prognosis. Cardiac death or myocardial infarction occurred in 5, 9 and 13% of the patients with a maximal troponin T level of < 0.06 (n = 154), 0.06-0.2 (n = 175) and > or = 0.2 microgram.l-1 (n = 437), respectively. Based on exercise tolerance and occurrence of ST depression, patients with a low (n = 361), intermediate (n = 325) and high risk (n = 80) exercise test response were identified. In these, death or myocardial infarction occurred in 5, 13 and 29%, respectively. The combination of troponin T and the exercise test response allowed an even better categorization into low (n = 84), intermediate (n = 406) and high (n = 276) risk groups with 1, 7 and 20% death or myocardial infarction, respectively. Among those 197 patients unable to perform an exercise test the incidence was 3, 16 and 27% in patients with troponin T < 0.06, 0.06-0.2 and > or = 0.2 microgram.l-1, respectively. Thus, troponin T determinations and pre-discharge exercise tests alone and combined are valuable for risk assessment in unstable coronary artery disease.

Aged↗