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Biomedical subjects

L Køber

Publications and source records attributed to L Køber.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Dofetilide to patients with heart failure and left ventricular dysfunction].

INTRODUCTION: Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction. METHODS: In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year. RESULTS: Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001). DISCUSSION: Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

Adult↗
PubMed2000

Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group.

BACKGROUND: We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. METHODS: Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. FINDINGS: Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p<O.001). For all five trials the ACE inhibitor group had lower rates of death than the placebo group (1,467/6,391 [23.0%] vs 1,710/6,372 [26.8%]; 0.80 [0.74-0.87]) and lower rates of reinfarction (571 [8.9%] vs 703 [11.0%]; 0.79 [0.70-0.89]), readmission for heart failure (876 [13.7%] vs 1202 [18.9%]; 0.67 [0.61-0.74]), and the composite of these events (2161 [33.8%] vs 2610 [41.0%]; 0.72 [0.67-0.78]; all p<0.0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.

Aged↗
PubMed2000

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.

OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. METHODS: This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). RESULTS: Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. CONCLUSIONS: Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.

Aged↗
PubMed2000

Long-term prognosis of diabetic patients with myocardial infarction: relation to antidiabetic treatment regimen. The TRACE Study Group.

AIMS: The present study was performed to evaluate pre-admission history, presentation, initial treatment and long-term mortality in patients with myocardial infarction and diabetes. METHODS AND RESULTS: Between 1990 and 1992, 6676 patients with acute myocardial infarction were screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study. In this cohort 719 (11%) of the patients had a history of diabetes. Among the diabetic patients 19% were treated with insulin, 52% with oral hypoglycaemic agents and 29% with diet only. The diabetic patients were slightly older, more likely to be female and had a higher prevalence of known cardiovascular disease. Even though the diabetic patients had the same frequency of ST-segment elevation on the electrocardiogram and the same admission delay, treatment with thrombolysis and aspirin was less frequently prescribed to the diabetic patients than to patients without diabetes. The mortality rate was significantly increased in the diabetic patients, 7-year mortality being 79% in insulin-treated, 73% in tablet-treated and 62% in diet-treated diabetic patients compared with 46% in patients without diabetes. In a multivariate analysis only diabetic patients treated with oral hypoglycaemic agents or with insulin had an increased mortality compared with non-diabetic patients. CONCLUSIONS: Patients with diabetes mellitus and myocardial infarction are treated with thrombolysis to a lesser extent than non-diabetic patients. Diabetic patients treated with oral hypoglycaemic agents or insulin, but not those treated with diet alone, have a significantly increased mortality following acute myocardial infarction compared with non-diabetic patients.

Aged↗
PubMed2000

Dofetilide: a class III anti-arrhythmic drug for the treatment of atrial fibrillation.

Dofetilide is a class III anti-arrhythmic drug that has been approved for the treatment of atrial fibrillation. Two clinical studies, which enrolled 996 patients, demonstrated pharmacological conversion to sinus rhythm to occur in 30% of patients. Following pharmacological or electrical conversion, median time to relapse exceeded one year. Two large clinical studies that enrolled 3028 patients have been performed in high-risk patients with severe heart failure and large myocardial infarctions. The outcomes of these studies were neutral with respect to survival and demonstrated the safety of dofetilide. After pharmacological or electrical conversion of atrial fibrillation to sinus rhythm in these studies, the probability of remaining in sinus rhythm during the following year was 75%. Dofetilide has a single significant side effect: risk of developing torsade de pointes ventricular tachycardia. Therefore, dosage must be carefully adjusted to the length of QTc interval, calculated creatinine clearance and the presence of heart failure or recent infarction. In addition, treatment must be initiated in hospital with three days of continuous telemetry. Dofetilide can be co-administered with digoxin and beta-blockers. Other anti-arrhythmic drugs, as well as drugs that interfere with the renal elimination or the metabolism of dofetilide, must be avoided. Dofetilide is an option when persistent atrial fibrillation is a clinical problem. In the setting of severe heart failure and large myocardial infarctions, only amiodarone and dofetilide have proven safety and dofetilide is a strong candidate for first choice treatment when the aim is to achieve sinus rhythm.

Animals↗
PubMed1999

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

Adult↗
PubMed1999

Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.

BACKGROUND: The survival benefit from the use of inhibitors of angiotensin-converting enzyme (ACE) in patients with acute myocardial infarction is usually presented in terms of risk ratios and lives saved per 1000 people treated. A more relevant way to present the extent of benefit would be in terms of an increase in life expectancy, but this approach has not previously been possible because of limited data on long-term outcome. We aimed to calculate the effect of trandolapril on life expectancy with follow-up data from the Trandolapril Cardiac Evaluation (TRACE) Study. METHODS: The TRACE study previously showed a significant survival benefit with trandolapril in patients with reduced left-ventricular function after an acute myocardial infarction who were treated for at least 2 years. We ascertained the survival status of all patients in the TRACE study in June, 1998, at which time they had been followed up for a minimum of 6 years. We estimated life expectancy as median lifetime, which was the time for 50% of the patients to have died. Change in life expectancy is expressed as change in median lifetime. Analysis was by intention to treat. FINDINGS: The life expectancy of patients was 4.6 years for those given placebo versus 6.2 years for those on trandolapril. Thus, for patients on trandolapril, median lifetime was increased by 15.3 months or 27% (95% CI 7 to 51). Analysis of follow-up after the end of the study indicated no decrease of this benefit during the course of double-blind treatment; continued use of trandolapril was recommended at study closure. INTERPRETATION: In patients with severely reduced left-ventricular function, long-term treatment with an ACE inhibitor during the critical period after myocardial infarction is associated with a substantial increase in life expectancy.

Adult↗
PubMed1999

Prognostic usefulness of repeated echocardiographic evaluation after acute myocardial infarction. TRACE Study Group. TRAndolapril Cardiac Evaluation.

The prognostic value of repeated echocardiographic measurement of left ventricular function after acute myocardial infarction was evaluated. We found that repeated measurements of wall motion index in survivors of acute myocardial infarction, with no reinfarction, provide important prognostic information about death and worsening of heart failure.

Aged↗
PubMed1999

Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation.

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

Aged↗
PubMed1999

Long-term prognostic importance of hyperkinesia following acute myocardial infarction. TRACE Study Group. TRAndolapril Cardiac Evaluation.

The long-term prognostic importance of hyperkinesia is unknown following an acute myocardial infarction (AMI). The American Society of Echocardiography recommends that hyperkinesia should not be included in calculation of wall motion index (WMI). The objective of the present study was to determine if hyperkinesia should be included in WMI when it is estimated for prognostic purposes following an AMI. Six thousand, six hundred seventy-six consecutive patients were screened 1 to 6 days after AMI in 27 Danish hospitals. WMI was measured in 6,232 patients applying the 9-segment model and the following scoring system: 3 for hyperkinesia, 2 for normokinesia, 1 for hypokinesia, 0 for akinesia, and -1 for dyskinesia. All patients were followed with respect to mortality for at least 3 years. WMI was calculated in 2 different ways: 1 including hyperkinetic segments (hyperkinetic-WMI) and the other excluding nonhyperkinetic segments (nonhyperkinetic-WMI) by converting the hyperkinetic segments to normokinetic segments. Hyperkinesia occurred in 736 patients (11.8%). WMI was an important prognostic factor (relative risk 2.49; p = 0.0001) for long-term mortality together with heart failure, history of hypertension, angina, or diabetes, previous AMI, age, thrombolytic therapy, arrhythmias, and bundle branch block. In a multivariate analysis including nonhyperkinetic-WMI, hyperkinesia was associated with a relative risk of 0.84, which was statistically significant (confidence intervals 0.74 to 0.96; p = 0.01). When hyperkinesia was included, both in WMI (hyperkinetic-WMI) and as an independent variable, no additional prognostic information (relative risk 0.93; p = 0.26) was obtained. An echocardiographic evaluation shortly after an AMI gave important prognostic information, especially if the information concerning hyperkinesia was included. If WMI is used for prognostic purposes, hyperkinesia should be included in calculation of the index.

Adult↗
PubMed1999

Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group.

OBJECTIVES: This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND: Patients with diabetes mellitus have a high mortality following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. METHODS: The study is a retrospective analysis using data from the Trandolapril Cardiac Evaluation (TRACE) study, which was a randomized, double-blind, placebo-controlled trial of trandolapril in 1,749 patients with AMI and ejection fraction < or =35%. The mean follow-up time was 26 months. RESULTS: A history of diabetes was found in 237 (14%) of the 1,749 patients. Treatment with trandolapril resulted in a relative risk (RR) of death from any cause for the diabetic group of 0.64 (95% confidence interval 0.45 to 0.91) versus 0.82 (0.69 to 0.97) for the nondiabetic group. In the diabetic group, trandolapril reduced the risk of progression to severe heart failure markedly (RR, 0.38 [0.21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. CONCLUSIONS: The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. TRACE Study group. TRAndolapril Cardiac Evalution.

AIMS: To investigate the occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. METHODS AND RESULTS: The occurrence and prognostic significance of atrial fibrillation/-flutter were studied in 6676 consecutive patients with acute myocardial infarction screened in 27 centres in Denmark for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study. Information about occurrence of atrial fibrillation/-flutter during hospitalization was prospectively collected for the following three periods: day 1-2, day 3-4 and from day 5 until discharge. A total of 1395 patients (21%) suffered from atrial fibrillation/-flutter in one or more of the specified periods during hospitalization. Patients with atrial fibrillation/-flutter were significantly older, a significantly greater proportion were women, left ventricular systolic dysfunction was more extensive, thrombolytic therapy was received less frequently, and anterior Q wave myocardial infarction was experienced more frequently than patients without atrial fibrillation/-flutter. History of acute myocardial infarction and/or angina pectoris was similar in patients with and without atrial fibrillation/-flutter, whereas significantly more patients with atrial fibrillation/-flutter had a history of hypertension, congestive heart failure, diabetes mellitus, pulmonary disease and stroke. The unadjusted in-hospital mortality rate was significantly higher in patients with atrial fibrillation/-flutter in one or more of the specified periods during hospitalization (18%) than in patients without atrial fibrillation/-flutter (9%), P<0.001. After adjustment for baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with increased in-hospital mortality; odds ratio=1.5 (95% Cl: 1.2-1.8), P<0.001. In patients surviving hospitalization, the unadjusted 5-year mortality rate was also significantly higher in patients suffering from atrial fibrillation/-flutter (56%) than in patients without atrial fibrillation/-flutter (34%), P<0.001. After adjustment for important prognostic baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with an increased mortality, relative risk=1.3 (95% Cl: 1.2-1.4). Subgroup analysis revealed that sustained atrial fibrillation/-flutter during hospitalization was associated with the highest risk of dying, relative risk=1.4 (95% Cl: 1.2-1.7). CONCLUSION: Atrial fibrillation/-flutter often occurs after acute myocardial infarction and our analysis demonstrated that it was an independent predictor of an increased short and long-term mortality.

Aged↗
PubMed1999

Spontaneous coronary artery dissection. Case report and literature review.

Primary coronary artery dissection occurring 2 months post partum in a 33-year-old woman is described. Owing to suspected acute myocardial infarction, the patient was treated with thrombolytic therapy but her condition deteriorated. Coronary angiography showed dissection of the left anterior descending artery (LAD). Her condition stabilized during treatment with intravenous heparin, aspirin, nitrates, beta-blockers, digoxin, ACE inhibitor and anticoagulants. At discharge she had no symptoms of heart failure. One hundred and forty one cases from the literature are reviewed with special reference to patient characteristics, patient treatment, and prognosis. Primary spontaneous coronary artery dissection is a rare condition but one that must be considered when young people, especially post partum women, present an acute ischaemic syndrome. Thrombolytic therapy may be a two-edged sword and therefore early angiography should be considered in making the diagnosis and choosing the therapy.

Adult↗
PubMed1999

The prognostic importance of smoking status at the time of acute myocardial infarction in 6676 patients. TRACE Study Group.

Smoking is an important risk factor for atherosclerotic heart disease, but several studies have shown smoking to be associated with a favourable prognosis in patients who have suffered an acute myocardial infarction (AMI). We studied a large group of consecutive patients admitted alive to hospital with an infarction in order to further study the prognostic importance of smoking status at the time of myocardial infarction. The study cohort comprised 6676 patients with an enzyme-confirmed myocardial infarction admitted to 27 Danish hospitals over a 26-month period between 1990 and 1992. Smoking status was determined at the time of hospitalisation and complete follow-up was obtained in October 1996. Smokers were on average 10 years younger, had fewer concomitant cardiac risk factors, and were more likely to be male and to receive thrombolytic therapy more frequently than non-smokers. In univariate analysis, smoking was associated with reduced 30-day and long-term mortality (risk ratio at 30 days 0.55, P < 0.001, risk ratio long-term 0.59, P < 0.001). When age only was included in a multivariate analysis, smoking was no longer of importance in short- or long-term mortality (risk ratio 0.92, P = 0.4 at 30 days and long-term risk ratio 0.98, P = 0.7). Inclusion of further variables did not change this picture. In conclusion, smoking contributes to the occurrence of AMI at a younger age. The more favourable prognosis in smokers at the time of AMI is a result of more favourable baseline characteristics, especially their lower age.

Chi-Square Distribution↗
PubMed1999

Age-distribution, risk factors and mortality in smokers and non-smokers with acute myocardial infarction: a review. TRACE study group. Danish Trandolapril Cardiac Evaluation.

Smoking is a risk factor for acute myocardial infarction; paradoxically, many studies have shown a lower post-infarct mortality among smokers. There are some important differences between smokers and non-smokers, which might explain the observed difference in mortality: smokers have less multivessel disease and atherosclerosis but are more thrombogenic; thrombolytic therapy seems to be more effective among smokers; smoking might result in an increased out-of-hospital mortality rate, by being more arrhythmogenic; and smokers are on average a decade younger than non-smokers at the time of infarction, and have less concomitant disease. Adjusting for these differences in regression analyses shows that smoking is not an independent risk factor for mortality after acute myocardial infarction. The difference in age and risk factors are responsible for the lower mortality among smokers.

Age Distribution↗