[Drugs for the prevention of death and recurrence after acute myocardial infarction].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
J F Hansen
Publications and source records attributed to J F Hansen.
[Verapamil therapy improves the prognosis after acute myocardial infarction. A review over the Danish studies of verapamil therapy during and after acute myocardial infarction].
The effect of verapamil therapy in a dosage of 120 thrice daily on the mortality and re-infarction from the time of admission and for the subsequent six months was investigated in a double-blind, randomized, placebo-controlled, multicentre investigation (The Danish Verapamil Infarction Trial (DAVIT I)). Seven hundred and seventeen patients were treated with verapamil and 719 with placebo. The mortalities after six months were 12.8% in the verapamil group and 13.9% in the placebo group (NS) and re-infarction occurred in 7.0% and 8.3%, respectively (NS). The effect of verapamil on the mortality and major events, i.e. death or the first re-infarction from the second week after an acute myocardial infarction was investigated in a double-blind, randomized, placebo-controlled, multicentre investigation (DAVIT II) in which 878 patients commenced treatment with verapamil in a dosage of 360 mg daily and 897 patients received a placebo. This treatment was continued for up to 18 months, on an average for 16 months. Ninety-five patients died and 146 major events were registered in the verapamil group while 119 died and 180 major events occurred in the placebo group. The 18 months mortality rates were 11.1 and 13.8% (hazard ratio 0.80, 95% confidence limits 0.63-1.05, p = 0.11) and the major event rates were 18.0 and 21.6% (0.80, 0.64-0.99, p = 0.03) in the verapamil and placebo groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Denmark↗
The significance of myocardial ischaemia and verapamil treatment on the prevalence of supraventricular tachyarrhythmias in patients recovering from acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.
Twenty-four hour Holter monitoring and symptom-limited exercise testing were carried out prior to discharge in 157 patients recovering from acute myocardial infarction. Supraventricular arrhythmias (SVT) during Holter monitoring were recorded in 15%, and ST segment depression during exercise in 27%. No association between exercise-provoked ischaemia and SVT was found in the late hospital phase of myocardial infarction. After the tests, patients were double-blindly randomized to treatment with verapamil 120 mg t.i.d. or placebo. One month after randomization 24 h Holter monitoring was repeated in 125 patients (verapamil = 63, placebo = 62). At one month a significantly increased incidence of SVT was found in the placebo group (25%) compared to the verapamil-treated patients (9%) (P = 0.04). The increased prevalence in the placebo group was mainly due to an increased incidence of SVT in patients with exercise-induced ischaemia (P = 0.03). This increment was blurred in the verapamil group. In conclusion, the prevalence of SVT increases during the first month after myocardial infarction. The increase is most pronounced in patients with residual myocardial ischaemia and seemed to be prevented by treatment with verapamil.
Double-Blind Method↗
Prevalence of transient myocardial ischaemia during the first year after a myocardial infarction. Effect of treatment with verapamil. The Danish Study Group on Verapamil in Myocardial Infarction.
DAVIT-II is a double-blind, randomized, multicentre, placebo-controlled study of long-term treatment with verapamil 360 mg per day administered to patients who have suffered an acute myocardial infarction (AMI). In the present study, comprising a subset of DAVIT-II, 48 h continuous ECG recordings demonstrated transient ST segment deviation indicative of myocardial ischaemia after one week, prior to randomization, in 18% (10 of 57) of the patients. After one month, 24% (11 of 46) of the placebo and 8% (3 of 39) of the verapamil-treated patients (P = 0.04) had myocardial ischaemia; after one year the figures were 26% (9 of 35) and 4% (1 of 27) (P = 0.02), respectively. At 18 months the 'major' event rate in patients who had had ischaemia before randomization was 40% and 23.8% in patients without ischaemia (P = 0.057). In the placebo group, 63% of 91 episodes of ST depression were recorded between 0600 h and 1800 h, and 62% of 26 episodes of ST elevation between 1800 h and 0600 h (P less than 0.001). Nine episodes of ST depression and no episode of ST elevation were recorded in the verapamil-treated patients. In conclusion, 20-25% of post-AMI patients have transient ischaemia; verapamil prevents ischaemia, and a pronounced circadian variation of ST segment deviations can be demonstrated.
Aged↗
Secondary prevention with calcium antagonists after acute myocardial infarction.
Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival and preventing reinfarction, nevertheless demonstrated pronounced differences between the 3 drugs. Nifedipine had no effect on reinfarction or death. Diltiazem had no overall effect but prevented first reinfarction or cardiac death (cardiac events) in patients without heart failure, and increased cardiac events in patients with heart failure before randomisation. Verapamil prevented first reinfarction or death (major events); the most pronounced effect was found in patients without heart failure before randomisation. Verapamil did not have detrimental effects in patients treated for heart failure before randomisation. Differences between trials and between drugs explaining the different clinical findings are evaluated.
Adrenergic beta-Antagonists↗
Insulin analogues with improved absorption characteristics.
The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.
Absorption↗
Physiological and pathophysiological pulmonary responses to inhaled nuisance-like or fibrogenic dusts.
A short-term bioassay has been developed to assess pulmonary toxicity and predict pathological effects in animals exposed to aerosolized particulates. To test the reliability and predictive value of our bioassay, we have exposed rats to 2 materials with different biological activities. Rats were exposed for 1 or 3 days to selected concentrations of crystalline silica (a known fibrogenic dust), or to carbonyl iron (CI) particles (a material with activity reputedly similar to nuisance dusts). Pulmonary cells and tissues were evaluated at several time points after exposure. In a companion manuscript we reported that brief exposures of silica produced a sustained pulmonary inflammatory response, characterized by increases in biochemical indicators, whereas no significant effects were measured in CI-exposed animals. In the current study, our results showed that although deposition patterns for the 2 dusts were similar (i.e., at alveolar duct bifurcations), brief doses of silica produced a sustained granulocytic inflammatory response at the sites of particle deposition, while CI particles were phagocytized and cleared from the lung by normal pulmonary macrophage mechanisms which included transport via the airway mucociliary escalator. Light, scanning, and transmission electron microscopy of silica-exposed lung tissue revealed a chronically active pulmonary inflammatory response characterized by hyperplasia of type II alveolar epithelial cells and the infiltration of pulmonary macrophages and neutrophils into interstitial tissues and alveoli. The lesions were progressive leading to a granulomatous pneumonitis within 2 months postexposure. In contrast to the alterations in pulmonary tissues produced by silica, no CI-related lesions were detected at any time postexposure. The results justify the utility of this bioassay as a reliable approach to evaluating the pulmonary toxicity of inhaled particulates.
Administration, Inhalation↗
Calcium antagonists and myocardial infarction.
In vitro and in vivo studies have demonstrated many similarities between the three calcium antagonists verapamil, nifedipine, and diltiazem in relation to protection of the myocardium during hypoxia. Important clinical differences exist between the three drugs when they are used during or after an acute myocardial infarction with the purpose of preventing death and reinfarction. The balance between the negative inotropic and the vasodilator properties and concomitant treatment with beta blockers may explain the results of clinical trials with the three calcium antagonists. Patients not treated with beta blockers. Nifedipine has been demonstrated to be no better than placebo both during and after an acute myocardial infarction. No placebo-controlled studies exist with diltiazem. Verapamil had no effect during the acute phase of a myocardial infarction. After a myocardial infarction, verapamil improved survival and reduced the reinfarction rate, an effect primarily found in patients without heart failure in the coronary care unit. Patients also treated with beta blockers. Nifedipine prevents the development of myocardial infarcts in patients with unstable angina. Diltiazem probably prevents reinfarction in the first two weeks after non-Q-wave infarction. Secondary prevention with diltiazem after an acute myocardial infarction had no overall effect on death or cardiac events (i.e., reinfarction or cardiac death). Subgroup analysis demonstrated in diltiazem-treated patients, compared with placebo-treated patients, a significant reduction of cardiac events in patients without and a significant increase of cardiac events in patients with heart failure. At present no indications exist for nifedipine during or after a myocardial infarction; further studies are needed with diltiazem, and verapamil may be used in secondary prevention of death and reinfarction.
Calcium Channel Blockers↗
Three-year mortality in patients suspected of acute myocardial infarction with and without confirmed diagnosis. The Danish Study Group on Verapamil in Myocardial Infarction.
The 3-year mortality from day 15 after admission was evaluated prospectively in 11,345 consecutive patients with chest pain suspected of myocardial infarction--4,265 patients with confirmed diagnosis (AMI) and 7,080 patients without confirmed diagnosis (non-AMI), respectively. The mortality rates per year in the first 3 years in the patients with AMI were 14.2%, 6.9%, and 7.6%, and in the non-AMI patients were 8.8%, 5.8%, and 5.5%. The standardized mortality ratio (SMR) correcting for age and sex differences was calculated. SMR is the ratio between the observed mortality in the study population and the expected mortality in an age- and sex-matched subgroup of the general background population. SMR in the first year was 6.7 (95% confidence limits: 6.2 to 7.2) in AMI and 4.7 (4.4 to 5.1) in non-AMI patients. In the second and third years of follow-up, SMR was 3.0 (2.6 to 3.4) and 2.9 (2.5 to 3.4) in AMI and 2.8 (2.5 to 3.1) and 2.4 (2.1 to 2.8) in the non-AMI patients. It is concluded that in the first 3 years the mortality of non-AMI patients is approximately three times higher than in the general population and very close to the late mortality of AMI patients, suggesting that the majority of non-AMI patients are suffering from ischemic heart disease also. Non-AMI patients should consequently be evaluated carefully prior to discharge.
Age Factors↗
QT interval in 24-hour ambulatory ECG recordings from 60 healthy adult subjects.
QT and RR intervals were measured in 24-hour electrocardiographic (ECG) recordings from 60 healthy subjects randomly selected among participants in the Copenhagen City Heart Study. Five men and five women of each 10-year age group between the ages of 20 and 79 were included. The mean of three consecutive RR and QT intervals was calculated from ECG strips recorded at 1000, 1400, 1800, 2200, 0200, and 0600 hours in each subject. The RR interval varied between 728 ms at 1400 hours and 984 ms at 0600 hours, and the uncorrected QT interval between 358 ms at 1400 hours and 417 ms at 0200 hours. The QT interval corrected for heart rate by Bazett's formula varied between 418 ms at 0600 hours and 428 ms at 1000 hours, and the QT interval corrected by the regression equation of this study varied between 396 ms at 1400 hours and 422 ms at 0200 hours. Multiple regression analysis of uncorrected data yielded a partial regression coefficient for heart rate influence of 0.14. After correction by Bazett's formula, a statistically significant effect of heart rate remained (partial regression coefficient -0.08, t = -9.93, p less than 0.0001). In addition to the influence of heart rate, the analysis revealed a statistically significant effect of hour of day (F = 11.30; DF 5, 286; p less than 0.0001) and gender (F = 6.24; DF 1, 53; p less than 0.05), whereas age in the range of 20-79 years had no significant effect. The QT intervals of this study differed from the values measured in standard ECG recordings but not from those of other Holter studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Development of a short-term inhalation bioassay to assess pulmonary toxicity of inhaled particles: comparisons of pulmonary responses to carbonyl iron and silica.
This paper describes a short-term inhalation bioassay for evaluating the lung toxicity of inhaled particulate materials. To validate the method, rats were exposed for 6 hr or 3 days to various concentrations of either aerosolized alpha-quartz silica or carbonyl iron particles. Cells and fluids from groups of sham- and dust-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, lactate dehydrogenase (LDH), and protein values were measured in BAL fluids at several time points postexposure. Cells were identified, counted, and evaluated for viability. Pulmonary macrophages (PM) were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy. The lungs of additional exposed animals were processed for histopathology and transmission electron microscopy. Brief exposures to silica elicited a sustained granulocytic inflammatory response (primarily neutrophils) with concomitant increases in alkaline phosphatase, LDH, and protein in the lavage fluids (p less than 0.05). In addition, PM functional capacity was depressed (p less than 0.05) and histopathologic lesions were observed within 1 month after exposure. In contrast, 6-hr or 3-day exposures to CI produced no cellular, cytotoxic, or alveolar/capillary membrane permeability changes at any time postexposure. PM function was either enhanced or unchanged from controls. These data demonstrate that short-term, high-dose inhalation exposures of silica produce effects similar to those previously observed using intratracheal instillation or chronic inhalation models, and lend support to this method as a reliable short-term bioassay for evaluating the pulmonary toxicity and mechanisms associated with exposures to new and untested materials.
Administration, Inhalation↗
The self-association of zinc-free human insulin and insulin analogue B13-glutamine.
The self-association of Zn-free human insulin, Zn-free insulin analogue B13-glutamine, 2-Zn insulin and cobalt(III) human insulin in the millimolar concentration range has been investigated by measuring the osmotic pressure at pH 7.5 in 0.05 M NaCl, 25 degrees C. The pH dependence of association has been measured in the pH range 6.8-9. For all insulins, except Zn-free human insulin, the major association state has been found to be the hexamer. Maximal association of hexamer has been observed for Zn-free human insulin at high concentration (2-7 mM) and physiological pH. At concentrations less than 1 mM and pH greater than 7.0, dissociation to a lower state than the hexamer is found. The conclusion has been drawn that, in the absence of metal ions, human insulin and insulin analogue B13-glutamine associate to the hexamer in the physiological pH range at concentrations in the millimolar range.
Humans↗
Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II).
The effect of verapamil on death, reinfarctions, and major events, i.e. death or reinfarction after a myocardial infarction has been investigated in 2 Danish double-blind placebo-controlled verapamil infarction trials (DAVIT I and II). DAVIT I was an early intervention trial that demonstrated a statistically nonsignificant reduction in mortality and reinfarction after 6 months of treatment. DAVIT II was a later intervention trial that demonstrated a nonsignificant reduction in the 18-month mortality rate [p = 0.11, hazard ratio 0.80; 95% confidence limits (CL) 0.61 to 1.05], a significant reduction in the reinfarction rate (p = 0.04, hazard ratio 0.77; CL 0.58 to 1.03), and in the major event rate (p = 0.03, hazard ratio 0.80; CL 0.64 to 0.99) in the verapamil group compared with the placebo group. In patients without heart failure in the coronary care unit, a statistically significant reduction in the 18-month mortality rate (p = 0.02, hazard ratio 0.64; CL 0.44 to 0.94), the reinfarction rate (p = 0.02, hazard ratio 0.67; CL 0.46 to 0.97), and the major event rate (p = 0.01, hazard ratio 0.70; CL 0.52 to 0.93) was observed in the verapamil group compared with the placebo group. No significant differences were found in patients with heart failure. Meta-analyses of DAVIT I (for patients alive at day 8) and DAVIT II showed a statistically significant reduction in the odds ratio of mortality (22%), reinfarctions (27%), and the major event rate (21%) in verapamil-treated patients. It is concluded that long term treatment with verapamil after an acute myocardial infarction is associated with a significant reduction in overall mortality, major events, and reinfarctions, with the greatest effect in patients without heart failure.
Angina Pectoris↗
Treatment with verapamil during and after an acute myocardial infarction: a review based on the Danish Verapamil Infarction Trials I and II. The Danish Study Group on Verapamil in Myocardial Infarction.
The effect of verapamil on death and reinfarction after an acute myocardial infarction was studied in two double-blind, randomized, placebo-controlled multicenter trials, the Danish Verapamil Infarction Trials I and II (DAVIT I and II). The studies demonstrated that verapamil 360 mg/day from the 2nd week after an acute myocardial infarction, prevented death and reinfarction. Meta-analyses of the results of DAVITs I and II resulted in a reduction of pooled ratios of 22% (95% confidence limits 1-37, p = 0.04) for death, 21% (5-35, p = 0.02) for first major events (first reinfarction or death), and 27% (6-43, p = 0.02) for first reinfarctions. The effect of verapamil was to prevent myocardial ischemia and reduce sudden death and reinfarction. It is concluded that long-term treatment with verapamil after an acute myocardial infarction may be recommended with the object of reducing overall mortality, major events and reinfarction.
Arrhythmias, Cardiac↗
Effect of verapamil on ischemia and ventricular arrhythmias after an acute myocardial infarction: prognostic implications. The Danish Verapamil Infarction Trial II Study Group.
This article is a review of presented subsets of the Danish Verapamil Infarction Trial II (DAVIT II) regarding the effect of verapamil on postinfarction ischemia, ventricular arrhythmias, and heart rate (HR), and the prognostic implications of these findings. Patients underwent Holter monitoring for 24-48 h at 1 week, i.e., before randomization to long-term treatment with placebo or verapamil, and after 1 month and about 1 year of study treatment. Ischemia: 18% of the patients had transient ST-segment deviation before randomization; 24% of the placebo- and 8% of the verapamil-treated patients (p = 0.04) showed ischemia after 1 month; and after 1 year, the figures were 26 and 4%, respectively (p = 0.02). The 18-month major event rate, i.e., first reinfarction or death, in patients with ischemia before randomization were 40 and 23.8% in patients without ischemia (p = 0.06). Arrhythmias: In the placebo group the prevalence and incidence of many ventricular ectopic beats (VEBs), i.e., more than 10 VEBs/h, increased significantly during the first years after infarction; this was not the case in the verapamil patients group. The mean HR was significantly reduced by verapamil treatment after 1 month and after 16 months of treatment. Multivariate analysis demonstrated the presence of more than 10 VEBs/h only early (i.e., 1 week) but not late (i.e., 1 month) after infarction, to be an independent predictor of major events during 18 months' follow-up observation. A HR above 80 beats/min independently predicted major events when appearing both early and late after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Propafenone versus quinidine slow-release for the treatment of chronic ventricular arrhythmias.
The efficacy and side-effects of oral propafenone 300 mg b.i.d. were compared to those of quinidine slow-release 800 mg b.i.d. in a randomized double-blind placebo controlled cross-over study in 12 patients with symptomatic premature ventricular complexes (PVCs). Furthermore during steady-state the plasma levels of propafenone and quinidine were measured repeatedly over an 8-hour period and correlated to the numbers of PVCs. In 6 patients both drugs reduced PVCs by 80%. In 2 patients this effect was obtained by propafenone and not by quinidine, while the reverse was found in another 2 patients. In 2 patients neither of the drugs was able to reduce PVCs by 80%. During treatment with quinidine 4 patients experienced diarrhoea and 1 patient suffered headaches taking propafenone. The plasma levels showed great variation. No correlation between the plasma levels expressed as area under the concentration-time curve and the reduction of PVCs was found.
Adult↗
Cryoprecipitate preparation.
Explore the source record for details and available documents.
Blood Preservation↗
Q waves and coronary artery disease.
In a consecutive series of 234 patients admitted for selective coronary arteriography, 78 had pathological Q waves. In 32 of these 78 patients, ECG showed left ventricular hypertrophy, QRS duration of greater than or equal to 0.12 sec, incomplete left bundle branch block, or left axis deviation. Fourteen (44%) of these 32 patients had coronary artery disease (CAD), while 40 (87%) of the remaining 46 patients without these ECG changes had CAD (p less than 0.0005). Among the 46 patients, 34 of 35 with angina pectoris had CAD compared to 6 of 11 without angina pectoris (p less than 0.01). Our study thus shows that Q waves may be reliable predictors of CAD especially in patients with angina pectoris.
Angina Pectoris↗