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Biomedical subjects

L Wallentin

Publications and source records attributed to L Wallentin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Early diagnosis and exclusion of acute myocardial infarction by two hours' vector-ECG and determination of either myoglobin or CK-mb. BIOMACS-study. BIOchemical Markers in Acute Coronary Syndromes.

This retrospective study assesses the early diagnostic potential of a combination of multilead continuous vectorcardiography (VCG) and biochemical markers (myoglobin, troponin-t and CK-mb mass) in patients with chest pain who present with suspected acute myocardial infarction (AMI), but without ST-elevation on resting 12-lead ECG on admission. Within a multicenter study 56 patients admitted for chest pain (< 12 h) and with a non-diagnostic 12-lead ECG on admission and a VCG recording were included. Venous blood samples were drawn on admission and the continuous VCG was monitored for 2 h. The results were related to the clinical diagnosis of AMI. Neither the biochemical markers nor VCG alone permitted the diagnosis or exclusion of AMI at admission. However, if either analysis of myoglobin on admission or 2 h of VCG recording were positive, they would have a sensitivity for detection of AMI of 100% and specificity of 69%. In a subset of patients with more than 4 h delay since start of chest pain, CK-mb could replace myoglobin and give a sensitivity of 100% and a specificity of 81%. Determination of myoglobin or CK-mb at admission and VCG monitoring for 2 h can reliably confirm or exclude AMI within 2 h. This combination seems useful for early stratifications of patients in chest pain or coronary care units.

Adult↗
PubMed2000

Reducing time to treatment in acute myocardial infarction.

The earliest possible initiation of reperfusion therapy is necessary to prevent extended necrosis, preserve ventricular function, and reduce morbidity and mortality from acute myocardial infarction. Therefore, improving the time to thrombolysis is a critical goal of patient management. Four complementary strategies have been employed in an attempt to shorten the time to thrombolytic therapy: (1) public education to shorten the delay in summoning help, (2) prehospital thrombolysis by trained emergency-response personnel, (3) implementation of emergency department thrombolysis protocols, (4) and the use of rapid diagnostic techniques to confirm acute myocardial infarction. Currently available fibrinolytic agents do not lend themselves to emergency use. Therefore, new thrombolytic agents have been bioengineered with characteristics that make them better suited for use in this setting. Two of these agents, TNK-t-PA and nPA, have extended half-life profiles that permit single-bolus dosing--an important consideration when fibrinolytic therapy is initiated outside the coronary care unit. The most effective system will integrate these complementary strategies to deliver continuous patient care from the time of the call for help, through emergency response, transportation, hospital admission, assessment, and initiation of thrombolytic therapy.

Clinical Protocols↗
PubMed2000

Prognostic value of ischemia monitoring with on-line vectorcardiography in patients with unstable coronary artery disease.

AIM: The aim of this study was to determine whether on-line vectorcardiography (VCG) gives independent prognostic information, regarding death, myocardial infarction (MI), and revascularization in patients with unstable coronary artery disease, i.e. unstable angina or non-Q-wave MI. METHODS AND RESULTS: One hundred and fifty patients (mean age 69 +/- 10), participating in a randomized study of low-molecular-weight heparin in unstable coronary artery disease, were studied with on-line VCG recordings for 24 h. During a 5-6-month follow-up, 11 patients died, 14 suffered a nonfatal MI and 31 were revascularized. Univariate predictors of death were diabetes mellitus (p < 0.01), maximum ST vector magnitude (ST-VM; p < 0.001), maximum ST change vector magnitude (STC-VM; p < 0.001), number of ST-VM (p < 0.01) and STC-VM episodes (p < 0.001). In multivariate analysis, the number of STC-VM episodes (p < 0.01) and diabetes mellitus (p < 0.02) each gave independent prognostic information regarding death. When all cardiovascular events were combined, the inability to perform an exercise test (p < 0.05), maximum value of ST-VM (p < 0.01) and STC-VM (p < 0.001), the number of episodes of STC-VM (p < 0.001) and ST-VM (p < 0.001) all gave prognostic information. In multivariate analysis, the inability to perform an exercise test and the number of STC-VM episodes were independent predictors. CONCLUSION: VCG monitoring during the first 24 h of hospitalization for unstable coronary artery disease gives independent prognostic information.

Adult↗
PubMed2000

Low-molecular-weight heparin as a bridge to timely revascularization in unstable coronary artery disease -- an update of the Fragmin during Instability in Coronary Artery Disease II Trial.

This article summarizes the design and findings -- both at 3 months and at 1 year follow-up -- of the Fragmin during Instability in Coronary Artery Disease (FRISC) II trial. This multicentre randomized trial compared both an early invasive with an early non-invasive stategy, and prolonged treatment with dalteparin as opposed to placebo, in patients with unstable coronary artery disease. The results show that an early invasive strategy with coronary angiography and, if appropriate, revascularization procedures within 7 days after admission reduces the subsequent rate of mortality and myocardial infarction. The benefits of the invasive treatment were noticeably more marked in patients with any high-risk indicator -- for example, male gender, age above 65 years, previous severe angina, or signs of ischaemia (ST depression on ECG) or of myocardial damage (elevated levels of troponin T). Treatment with dalteparin reduced the risk of death and myocardial infarction in high-risk (i.e. troponin-positive) patients, particularly during the first month of treatment. However, continuation with dalteparin therapy after revascularization procedures conferred no benefit. It is concluded that extended treatment with dalteparin is useful as a bridge to revascularization in this high-risk subgroup of patients with unstable coronary artery disease.

Algorithms↗
PubMed2000

Low molecular weight heparin in unstable coronary artery disease.

Since the recognition that any thrombosis overlying a ruptured atherosclerotic plaque is a central component of the pathogenesis of unstable coronary artery disease (CAD), a number of antithrombotic treatment strategies have been investigated in randomised clinical trials. Aspirin reduces the occurrence of symptomatic and silent ischaemia, myocardial infarction (MI) and death in patients with unstable CAD, both in the acute phase and during continued long-term treatment and is now considered routine therapy. The addition of unfractionated heparin infusion further reduces cardiac events during the treatment period, but is not associated with any sustained benefits during long-term follow-up. Low molecular weight heparins (LMWHs) are completely absorbed by the sc. route. A predictable anticoagulant effect is maintained by sc. injections every 12 - 24 h without laboratory monitoring. The FRISC trial demonstrated that, in conjunction with aspirin, the LMWH dalteparin reduced death and MI by more than 50% in the acute phase. Four similar trials have directly compared LMWH with unfractionated heparin and demonstrated at least the same efficacy in the acute phase, treated between three and eight days. The LMWH enoxaparin was more effective at reducing death or MI than unfractionated heparin infusion during the three days of treatment, an effect which lasted up to 12 months. Prolonged out-patient treatment beyond the acute phase has been evaluated in four trials. It was demonstrated, in two of these trials, that continuing twice-daily injections of dalteparin further reduced the risk of death, MI and need for revascularisation at least during the initial six weeks of treatment. This effect was confined, however, to patients with signs of myocardial damage, i.e., elevation of troponin, at admission. During prolonged out-patient treatment, there is an increased risk of severe bleeding due to the combination of LMWH with aspirin. Based on successful results, the LMWHs, having the convenience of treatment and the option for continuation in an out-patient setting, should replace unfractionated heparin as the routine treatment in unstable CAD. If an early invasive procedure is considered, the LMWH therapy should be continued until the intervention as a 'bridge-to-revascularisation'. New antiplatelet agents are also emerging as additional useful tools for treating these patients, thus it is urgent to evaluate the comibination of these new therapies with the LMWHs.

Angina, Unstable↗
PubMed1999

ST-segment monitoring with continuous 12-lead ECG improves early risk stratification in patients with chest pain and ECG nondiagnostic of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the prognostic importance of ischemic episodes detected by ST-segment monitoring with continuous 12-lead electrocardiography (ECG) in a nonselected coronary care unit (CCU) population with chest pain and ECG nondiagnostic of acute myocardial infarction (AMI). BACKGROUND: Patients with chest pain and ECG nondiagnostic of AMI constitute a heterogeneous group concerning both diagnosis and prognosis. Continuous 12-lead ECG is a rather new method not thoroughly studied in this population. METHODS: The ST-segment monitoring with continuous 12-lead ECG was performed for 12 h in 630 consecutive patients admitted to CCU due to chest pain and a nondiagnostic ECG, i.e., no ST-segment elevations. An ST-episode was defined as a transient ST-segment depression or elevation of at least 0.10 mV. The median follow-up time was six months. RESULTS: A total of 176 ST-episodes occurred in 100 (15.9%) patients. The median duration and maximal ST-segment deviation in patients with ST-episodes were 80 min and 0.20 mV, respectively. Presence of ST-episodes predicted worse outcome concerning cardiac death and cardiac death or myocardial infarction (MI) (log-rank p < 0.001). At 30 day follow-up procedure, 10% versus 1.5% died from cardiac causes or had an MI in the group with and without ST-episodes, respectively. In a multivariate analysis, only troponin T > or = 0.10 microg/l and the presence of ST-episodes came out as independent predictors of cardiac death or MI. CONCLUSIONS: Continuous 12-lead ECG monitoring provides prognostic information on-line and considerably improves early risk stratification in patients with ECG nondiagnostic of AMI and symptoms suggestive of acute coronary syndrome.

Aged↗
PubMed1999

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Aged↗
PubMed1999

Management strategies in unstable coronary artery disease--current problems and future directions. The UCAD Council.

Unstable coronary artery disease continues to pose a major challenge to clinicians. The advent of new therapies, such as percutaneous transluminal coronary angioplasty, low-molecular-weight heparins, and glycoprotein IIb/IIIa inhibitors, provides new management options for this indication but also raises new questions with regard to optimal management. Prospective randomized trials with well-defined, long-term outcome measures and a means of identifying which patients will derive most benefit from each treatment, together with a means of rapid and clear dissemination of study results and implications, are required in order to advance the management of unstable coronary artery disease.

Angina, Unstable↗
PubMed1999

Influences of sex and smoking habits on anticoagulant activity in low-molecular-weight heparin treatment of unstable coronary artery disease.

BACKGROUND: In the FRISC trial, dalteparin 120 IU/kg body weight twice daily for unstable coronary artery disease was safe and reduced the risk of new coronary events. This risk reduction was maintained during the following extended treatment with a fixed dose of 7500 IU dalteparin once daily. METHODS AND RESULTS: Minor bleeding was more frequent in women compared with men: relative risk (CI) 2.88 (1.78 to 4.67) during the weight-adjusted and 2.36 (1.37 to 2.63) during the fixed dose treatment. The anti-Xa activity determined in samples (n = 175) obtained during the acute phase treatment was higher in women compared with men (P <.001) and in nonsmokers compared with smokers (<.001) in multiple regression analysis. Also, during the fixed-dose treatment (n = 131) an independent relation between anti-Xa activity and sex (P <.001), but not smoking habits, persisted. CONCLUSION: To improve future low-molecular-weight heparin dose regimens for the treatment of acute coronary syndromes, it might be important to consider the influence of sex and smoking habits.

Adult↗
PubMed1999

Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction--a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II).

OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study.

Adult↗
PubMed1999

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease.

AIM: This study evaluated a novel specific thrombin inhibitor, inogatran, in comparison with unfractionated heparin, with regard to markers for coagulation activity in patients with unstable coronary artery disease. METHODS AND RESULTS: In the Thrombin Inhibition In Myocardial Ischaemia (TRIM) study patients were randomized to one of three different doses of inogatran or to unfractionated heparin, given intravenously over 72 h. In a subpopulation of 320 patients, markers for coagulation activity were measured at baseline, during and after the study infusion. Prothrombin fragment 1 + 2, indicating thrombin generation, decreased in the low, medium and high dose inogatran groups and in the heparin group during the first 6 h of treatment by 12%, 15%, 21% and 26%, respectively. From 6 h to 72 h after the start of infusion the levels changed by -7%, -6%, -4% and +34%, respectively. The increase in the heparin group continued after the infusion was stopped. Thrombin-antithrombin complex, also indicating thrombin generation, decreased by 0%, 2%, 18% and 22%, respectively, during the first 6 h of treatment. During the same period soluble fibrin, an intermediate in fibrin formation, increased both in the low and medium inogatran group by 9%, while a decrease by 4% and 18%, respectively, was seen in the high dose inogatran group and in the heparin group. Fibrin dissolution, as measured by fibrin D-dimer, decreased during the first 24 h of treatment by 20%, 18%, 18% and 20%, respectively. The first 24 h after discontinuation of infusion, fibrin D-dimer increased by 6%, 23%, 25% and 44%, respectively. After 72 h, at the end of infusion, patients treated with inogatran, to a larger extent than those given heparin, had suffered from death, myocardial infarction or refractory angina pectoris. After 7 days this trend was less marked. CONCLUSION: The more pronounced decrease in thrombin generation and fibrin turnover during the first 6 h of infusion, and the later increase in thrombin generation and fibrin turnover, in the heparin group, as compared to the inogatran groups, may be related to the lower clinical event rate during infusion with heparin compared with inogatran and the recurrence of ischaemic events, early after cessation of heparin infusion.

Aged↗
PubMed1999

Reduction of myocardial damage by prolonged treatment with subcutaneous low molecular weight heparin in unstable coronary artery disease. FRISC study group. Fragmin during Instability in Coronary Artery Disease.

AIMS: Several studies have proved heparin useful in treating patients with unstable coronary artery disease. The present study investigates whether Selvester QRS scoring for estimation of myocardial infarct size increases the incidence of detection of acute myocardial infarction during follow-up in a trial of patients with unstable angina/non-Q wave myocardial infarction treated with low molecular weight heparin or placebo. Finally it will be discussed how the QRS score, used for end-point identification, impacts on the power calculation in clinical trials. METHODS AND RESULTS: Electrocardiographic data on 1276 patients (644 in the placebo group, 632 in the low molecular weight heparin treatment group) were available. All ECGs were scored according to the Selvester QRS scoring method. At 40 days, more patients in the placebo than in the heparin group had achieved a threshold level of QRS score (25.9% vs 21.1%, P=0.05). Myocardial infarction, diagnosed as per the classic Q wave criteria, occurred in 3.7% of patients in the placebo group and in 0.9% in the low molecular weight heparin group at 6 days (P=0.002). At 40 days, the rates were 8.2% (placebo) and 5.7% (low molecular weight heparin, P=0.2). By combining the classic criteria with the Selvester method the myocardial infarction end-point rate in both groups was almost doubled (8.2% to 14.4% in the placebo group and 5.7% to 11.1% in the low molecular weight heparin group, P=0.07). The 216 patients with non-evaluable electrocardiograms did not differ from the 1276 patients as regards baseline characteristics; however, they had a significantly poorer prognosis, with a death/myocardial infarction rate of 20% at 40 days, compared with 8% among the patients with evaluable electrocardiograms (P<0.00001). CONCLUSION: Long-term subcutaneous treatment with low molecular weight heparin decreases the number of subsequent myocardial infarctions - determined both conventionally and by an increase in QRS score - in patients with unstable coronary artery disease. Silent myocardial infarctions detected by QRS score, as well as clinical myocardial infarctions, could be used as end-points in clinical trials of ischaemic heart disease and thus lower the population needed for obtaining statistical power.

Aged↗
PubMed1999

The impact of an end-point committee in a large multicentre, randomized, placebo-controlled clinical trial: results with and without the end-point committee's final decision on end-points.

BACKGROUND: A multicentre study permits rapid recruitment of a large number of patients. However, there is a risk of heterogeneities in end-point evaluations, as complex definitions of criteria are interpreted by several local investigators from different hospitals. Reports discussing end-point evaluation are sparse. The TRIM trial was a multicentre trial of a thrombin inhibitor in patients with unstable angina or non-Q myocardial infarction. In this study, an independent end-point committee evaluated all the reported events of death, acute myocardial infarction and refractory angina pectoris in order to obtain uniform judgements of major end-points. STUDY AIMS: To describe the work of the end-point committee, to analyse its possible effect on the final study results and to discuss the impact on the design of future trials. METHOD: The end-point committee consisted of four members, one from each participating country. After the data were processed by the study monitors, completed case record forms and patient files for patients with reported end-points were mailed to the national member of the end-point committee for judgement. The end-point committee met regularly and made final decisions about the end-points. The work of the end-point committee was documented on a separate case record form. RESULTS: The end-point committee assessed 246 events of death, acute myocardial infarction and refractory angina pectoris in 187 of the 1209 patients (15.5%) in the TRIM trial. Misinterpretation of the index event, an inclusion myocardial infarction, as an early cardiac event was found in 12 patients. After end-point committee judgements, the number of patients with acute myocardial infarction or refractory angina pectoris during 30 days of follow-up was reduced from 177 to 153 (13. 6% reduction). The classification of events was changed in 53 of 187 patients (28.3%) with death, acute myocardial infarction or refractory angina pectoris. The data assessed by the safety committee was significantly different from the final database after end-point committee judgements. CONCLUSION: The end-point committee corrected misinterpretations in such a high proportion of cases that the final results differed significantly from the preliminary results delivered to the safety committee. End-point judgements by an end-point committee should be performed in multicentre clinical trials to improve the quality and reliability of study results.

Anticoagulants↗
PubMed1999

Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease.

UNLABELLED: Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina. Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were randomized to 72 h infusion with inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between inogatran and unfractionated heparin treatment as regards clinical outcome. 11.6% of the 464 inogatran treated patients with activated partial thromboplastin time above the median at 6 h (44 s) had a clinical event in 7 days, and 6.6% of the 423 patients with activated partial thromboplastin time below the median (P=0.01). After 30 days the event rate was still 41% higher in the inogatran patients with activated partial thromboplastin time above the median (P=0.06). Activated partial thromboplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, during heparin infusion there was a trend for improved clinical outcome with activated partial thromboplastin time above the median, but this benefit was lost after cessation of treatment. CONCLUSIONS: Higher activated partial thromboplastin time levels during inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at least in part, be explained by differences in anticoagulant mechanisms between direct thrombin inhibitors and heparin, and further emphasizes the poorly defined optimal activated partial thromboplastin time range during treatment with direct thrombin inhibitors in unstable coronary artery disease.

Adult↗