Ventricular fibrillation following administration of thrombolytic treatment: The EMIP experience

Reperfusion-induced ventricular fibrillation has been dem onstratedin animal models of myocardial ischaemia, but no evidence existsfor this in humans. The European Myocar dial Infarction Projectcompared the efficacy and safety of pre-hospital thrombolytictherapy with that of hospital therapy. The objective of thisstudy was to investigate the occurrence of reperfusion-inducedventricular fibrilla tion in acute myocardial infarction patientsfollowing thrombolytic therapy. In a double-blind multicentre trial, eligible patients wererandomized to receive anistreplase at home followed by placeboin the hospital (A/P group), or placebo followed by anistreplase(P/A group). The occurrence of ventricular fibrillation, andother adverse events were recorded on specific study forms andcould be attributed to defined time intervals. The incidence of ventricular fibrillation in the A/P group wassignificantly higher following the pre-hospital injection thanin the P/A group (2.5% vs 1.6%; P=0.021); the situation wasreversed following the hospital injection (3.6% vs 5.3%; P=0.002).No relationship was found be tween this excess of ventricularfibrillation and the patients condition, with the exceptionof the site of the infarct. These results suggest the existence of reperfusion-induced ventricularfibrillation in patients developing myocardial infarction whoreceive thrombolytic treatment.     

Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study.

The Medical Patients with Enoxaparin (MEDENOX) trial was a randomized, placebo-controlled study that defined the risk of venous thromboembolism (VTE) in acutely ill, immobilized, general medical patients and the efficacy of the low-molecular-weight heparin, enoxaparin, in preventing thrombosis. We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness (heart failure, respiratory failure, infection, rheumatic disorder and inflammatory bowel disease) and pre-defined risk factors (chronic heart and chronic respiratory failure, age, immobility, previous VTE and cancer). The primary outcome was the occurrence of documented VTE between days 1 and 14. The relative risk reduction [95% confidence intervals (CI)] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were: acute heart failure, 0.29 (95% CI, 0.10-0.84); acute respiratory failure, 0.25 (95% CI, 0.10-0.65); acute infectious disease, 0.28 (95% CI, 0.09-0.81); and acute rheumatic disorder, 0.48 (95% CI, 0.11-2.16). The relative risk reduction for VTE in the pre-defined risk factor subgroups were: chronic heart failure, 0.26 (95% CI, 0.08-0.92); chronic respiratory failure, 0.26 (95% CI, 0.10-0.68); age, 0.22 (95% CI, 0.09-0.51); immobility, 0.53 (95% CI, 0.14-1.72); previous VTE, 0.49 (95% CI, 0.15-1.68); and cancer, 0.50 (95%o CI, 0.14-1.72). The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients.     

Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction: Analysis of data from the EMIP study

OBJECTIVES: To compare the components of the time delay involved in pre-hospitaland hospital thrombolytic therapy in patients presenting withsuspected acute myocardial infarction. MATERIAL AND METHODS: From October 1988 to January 1992 a total of 198 mobile emergencyunits in 15 European countries and Canada randomized 5469 patientsto receive either pre-hospital thrombolytic treatment, followedby placebo in hospital (pre-hospital group), or pre-hospitalplacebo, followed by thrombolytic treatment in hospital (hospitalgroup) in the European Myocardial Infarction Project trial.We performed a post hoc analysis of these data to correlatecomponents of the interval between symptom onset and treatmentwith baseline patient characteristics. RESULTS: The delay between onset of symptoms and calling for an ambulancewas significantly longer for female patients (P0·0001),older patients (>65 years old; P=0·0001), those whohad experienced pain within the previous 24 h (P=0·0001),and those with pulmonary oedema (P=0·04). This delaywas significantly shorter in patients with previous myocardialinfarction (P=0·02), those with ventricular fibrillation(P=0·0001), and those in shock (P0·0001). Thedelay between the two injections was significantly longer forolder patients (>65 years old; P=0·02), those withprevious myocardial infarction (P=0·03), and those inshock (P=0·003). CONCLUSIONS: Action undertaken to reduce delays between symptom onset andtreatment should focus on modifiable factors such as patientswho are likely to be late callers, i.e. women and those over65 years of age.     

Long-term consequences of deep vein thrombosis

Following an overt episode of deep vein thrombosis (DVT), the long-term prognosis of the patient is predominantly obscured by three natural complications: recurrence of venous thromboembolism (VTE), post-thrombotic syndrome and death. Antithrombotic treatments have been proven effective in preventing recurrence of VTE but carry the risk of major bleeding. A high mortality rate persists during the first year following an acute VTE, with a small but continuing risk beyond the first year. Recurrences of VTE account for the minority of causes of deaths. With effective initial anticoagulant treatment, the early (within approximately 3 months) risk of recurrence is 3-6%. Long-term follow-up studies have shown that although the risk of recurrence of VTE beyond the first 6 months is lower, the risk persists over several years. Approximately 25% of DVT patients remain asymptomatic in the long term but severe signs of post-thrombotic syndrome (ulceration) are observed in 2-10% of patients 10 years after DVT. Major advances have been made in the management of acute VTE but the excess risks of death, recurrence of VTE and post-thrombotic syndrome persist for several years following the initial event. Appropriate therapeutic strategies for these events are still being developed and future study should be directed towards finding the optimal regimen for patients who require prolonged treatment.     

Primary angioplasty is cost-minimizing compared with pre-hospital thrombolysis for patients within 60 min of a percutaneous coronary intervention center: the Comparison of Angioplasty and Pre-hospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) cost-efficacy sub-study

OBJECTIVES: This ancillary study of the Comparison of Angioplasty and Pre-hospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) trial sought to assess the cost-efficacy ratio of primary coronary angioplasty (PCA) and pre-hospital thrombolysis (PHT) in patients suffering from an acute myocardial infarction (AMI) (<6 h) close to (<60 min journey) a percutaneous coronary intervention (PCI) center. BACKGROUND: In the CAPTIM study, at 30 days follow-up PCA was as equally effective as PHT with rescue angioplasty if needed. The cost efficacy of these two strategies has not yet been compared. METHODS: Data were prospectively collected for 299 patients in three centers. The efficacy analysis was extended at one-year follow-up for those patients. Direct fixed and variable actual costs were assessed with a piggyback data collection. RESULTS: The one-year primary end point event-rate (death, non-fatal myocardial infarction, and stroke) was not different after PCA or PHT (14% vs. 16. 4%, p = NS). Costs were lower in the PCA group either during the in-hospital period (8,287 vs. 9,170 $, p = 0.0001) and after one-year follow-up, in relation to a higher rate of subsequent revascularizations in the PHT group (49% vs. 23%, p < 0. 01), leading to a longer hospital stay (10 vs. 9.1 days, p = 0. 03). CONCLUSIONS: After AMI in patients less than 1 h from a PCI center, PCA is as effective and less costly than a combined strategy of PHT followed by rescue angioplasty.     

A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients

Evaluation of the accuracy of ultrasound has yielded heterogeneous results. Our objective was to summarize the evidence on the accuracy of ultrasound compared to venography in asymptomatic patients, taking into account the variation due to threshold differences. Searches of journal table of contents, computer databases (Medline, Embase, Biomed, Cochrane) and conference proceedings were performed. A study was eligible if it prospectively compared ultrasound to venography for the diagnosis of DVT in asymptomatic patients. Data of studies selected for inclusion were extracted independently by two authors. High quality studies with consecutive patient enrollment, blind evaluation of the two techniques, and absence of verification bias are summarized as Level 1, while those not fulfilling one or more of these criteria are considered Level 2. Original study authors were contacted to confirm accuracy and to provide missing data. A pooled estimate of the accuracy of ultrasound was obtained according to the method of Moses and coworkers. This method gives a summary diagnostic odds ratio (DOR). The DOR is a single indicator of test performance. It varies between 0 and infinity and exceeds 1, only when ultrasound is more often positive in patients with DVT relative to those without DVT. Higher DOR indicates better discriminatory test performance. Thirty one studies were rated as potentially unbiased and graded as Level 1. The mean prevalence of DVT as determined by venography was 22%. In Level 1 studies, the odds of positive ultrasound in proximal veins was 379 times higher (95% confidence limits 65, 2,200) and in distal veins 32 times higher (7.5, 135) among patients with DVT than those without. Our results suggest that, particularly for proximal veins, ultrasound is accurate for the diagnosis of DVT in asymptomatic postoperative orthopedic patients. More research is needed in other clinical settings.     

Controlled clinical trial for the comparison of tolerance of two aldosterone antagonists

ETAHP was a randomized multicentre study in general practice. The objective of the study was to assess the clinical safety of RU 28318, a new aldosterone antagonist, compared with spironolactone. 80 hypertensive patients were recruited by 52 general practitioners and treated with 160 mg of RU 28318 or 80 mg spironolactone (the doses had previously shown to be pharmacologically equivalent) for one year. The main end-point was the occurrence of gynecomastia. During the follow-up period, 18 gynecomastia were observed, 7 in the RU 28318 group and 11 in the spironolactone group, after 4 to 5 months of treatment. This difference is not statistically significant (p = 0.15). There were no statistically significant differences for the other clinical or biological end points. Centralized randomized allocation of treatment and transmission of data were carried out using a telematic system (the French Minitel system). The observed rate of gynecomastia in the RU 28318 group, not statistically different from that in the spironolactone group, was in agreement with the results of others studies conducted at the same time and resulted in the discontinuation of the development of the molecule.     

Relative efficacy of angiotensin converting enzyme inhibitors on mortality of patients with congestive heart failure: implications of randomized trials and role of the aetiology (ischaemic or non-ischaemic) of heart failure.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.