Magnitude of benefit from earlier thrombolytic treatment in acute myocardial infarction: new evidence from Grampian region early anistreplase trial (GREAT)
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OBJECTIVE: To generalise from the results of the Grampian region early anistreplase trial (GREAT) and to express the benefit of earlier thrombolysis in terms of lives saved per hour of earlier treatment. DESIGN: Multivariate analysis of a randomised double blind trial. SETTING: 29 rural practices in Grampian region and teaching hospitals in Aberdeen. SUBJECTS: 311 patients with suspected acute myocardial infarction and without contraindications to thrombolysis who were seen by their general practitioners within four hours of the start of symptoms. INTERVENTIONS: Anisterplase 30 units given intravenously, either by general practitioners before hospitalisation or later in hospital. MAIN OUTCOME MEASURE: Death within 30 months of entry into trial. RESULTS: Death within 30 months was positively related to age (P < 0.0001) and to delay between start of symptoms and thrombolytic treatment (P = 0.0004). However, the probability of dying rose exponentially with earlier presentation, so death within 30 months was negatively related to the logarithm of the time of randomisation (P = 0.0163). In patients presenting two hours after start of symptoms each hour's delay in receiving thrombolysis led to the loss of 21 lives per 1000 within 30 days (95% confidence interval 1 to 94 lives per 1000) (P = 0.03) and 69 lives per 1000 within 30 months (16 to 141 lives per 1000) (P = 0.0004). CONCLUSIONS: The magnitude of the benefit from earlier thrombolysis is such that giving thrombolytic treatment to patients with acute myocardial infarction should be accorded the same degree of urgency as the treatment of cardiac arrest. (+info)
Ventricular fibrillation following administration of thrombolytic treatment. The EMIP experience. European Myocardial Infarction Project.
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Reperfusion-induced ventricular fibrillation has been demonstrated in animal models of myocardial ischaemia, but no evidence exists for this in humans. The European Myocardial Infarction Project compared the efficacy and safety of pre-hospital thrombolytic therapy with that of hospital therapy. The objective of this study was to investigate the occurrence of reperfusion-induced ventricular fibrillation in acute myocardial infarction patients following thrombolytic therapy. In a double-blind multicentre trial, eligible patients were randomized to receive anistreplase at home followed by placebo in the hospital (A/P group), or placebo followed by anistreplase (P/A group). The occurrence of ventricular fibrillation, and other adverse events were recorded on specific study forms and could be attributed to defined time intervals. The incidence of ventricular fibrillation in the A/P group was significantly higher following the pre-hospital injection than in the P/A group (2.5% vs 1.6%; P = 0.021); the situation was reversed following the hospital injection (3.6% vs 5.3%; P = 0.002). No relationship was found between this excess of ventricular fibrillation and the patients' condition, with the exception of the site of the infarct. These results suggest the existence of reperfusion-induced ventricular fibrillation in patients developing myocardial infarction who receive thrombolytic treatment. (+info)
A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial.
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OBJECTIVE: To compare aspirin with anticoagulation with regard to risk of cardiac death and reinfarction in patients who received anistreplase thrombolysis for myocardial infarction. DESIGN: A multicentre unblinded randomised clinical trial. SETTING: 38 hospitals in six countries. SUBJECTS: 1036 patients who had been treated with anistreplase for myocardial infarction were randomly assigned to either aspirin (150 mg daily) or anticoagulation (intravenous heparin followed by warfarin or other oral anticoagulant). The trial was stopped earlier than originally intended because of the slowing rate of recruitment. MAIN OUTCOME MEASURE: Cardiac death or recurrent myocardial infarction at 30 days. RESULTS: After 30 days cardiac death or reinfarction, occurred in 11.0% (57/517) of the patients treated with anticoagulation and 11.2% (58/519) of the patients treated with aspirin (odds ratio 1.02, 95% confidence interval 0.69 to 1.50, P = 0.92). Corresponding findings at three months were 13.2% (68/517) and 12.1% (63/519) (0.91, 0.63 to 1.32, P = 0.67). Patients receiving anticoagulation were more likely than patients receiving aspirin to have had severe bleeding or a stroke by three months (3.9% v 1.7% (0.44, 0.20 to 0.97, P = 0.04)). CONCLUSION: No evidence of a difference in the incidence of cardiac events was found between the two treatment groups, though the trial is too small to claim treatment equivalence confidently. A higher incidence of severe bleeding events and strokes was detected in the group receiving anticoagulation, suggesting that aspirin may be the drug of choice for most patients in this context. (+info)
Thrombolysis after acute myocardial infarction.
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Appropriate use of a thrombolytic agent may save 20 to 30 lives per 1000 treatments. Thrombolysis should be considered in all patients presenting with cardiac chest pain lasting more than 30 minutes for up to 12 hours after symptom onset. ECG criteria include ST elevation of at least 1 mm in limb leads and/or at least 2 mm in two or more adjacent chest leads or left bundle branch block. There is no upper age limit. All patients should also receive oral aspirin and subcutaneous (intravenous with rt-PA) heparin. Other adjuvant treatments have been reviewed previously in this journal. Streptokinase is the drug of choice except where there is persistent hypotension, previous streptokinase or APSAC at any time, known allergy to streptokinase, or a recent proven streptococcal infection. In these circumstances the patient should receive rt-PA. Additional indications for rt-PA, based on subset analysis by the GUSTO investigators, include patients with ALL of the following: age less than 75 years, presentation within four hours of symptom onset, and ECG evidence of anterior acute myocardial infarction. Treatment should be initiated as soon as possible. The greatest benefit is observed in patients treated early, pain to treat intervals of less than one hour make possible mortality reductions of nearly 50%. "When" matters more than "where": fast tracking to the CCU is one option but A&E initiated thrombolysis is feasible and timely. Prehospital thrombolysis is appropriate in certain geographical situations. The development of practical guidelines for thrombolysis represents the most comprehensive example of evidence based medicine. Streptokinase was first shown to influence outcome in acute myocardial infarction nearly 40 years ago. More recently alternative regimes have been evaluated in several prospective randomised controlled trials yielding pooled data on nearly 60,000 patients. However, systematic review of cumulative data reveals a statistically significant mortality gain for intravenous streptokinase over placebo which could have been identified as early as 1971-at least 15 years before it became generally used in clinical practice. (+info)
An economic evaluation of thrombolysis in a remote rural community.
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OBJECTIVES: To assess the cost effectiveness of community thrombolysis relative to hospital thrombolysis by investigating the extra costs and benefits of a policy of community thrombolysis, then establishing the extra cost per life saved by community thrombolysis. DESIGN: Economic evaluation based on the results of the Grampian region early anistreplase trial. SETTING: 29 rural general practices and one secondary care provider in Grampian, Scotland. SUBJECTS: 311 patients recruited to the Grampian region early anistreplase trial. INTERVENTIONS: Intravenous anistreplase given either by general practitioners or secondary care clinicians. MAIN OUTCOME MEASURES: Survival at 4 years and costs of administration of thrombolysis. RESULTS: Relative to hospital thrombolysis, community thrombolysis gives an additional probability of survival at 4 years of 11% (95% confidence interval 1% to 22%) at an additional cost of 425 pounds per patient. This gives a marginal cost of life saved at 4 years of 3,890 pounds (1,990 pounds to 42,820 pounds). CONCLUSIONS: The cost per life saved by community thrombolysis is modest compared with, for example, the cost of changing the thrombolytic drug used in hospital from streptokinase to alteplase. (+info)
Quantification of the benefit of earlier thrombolytic therapy: five-year results of the Grampian Region Early Anistreplase Trial (GREAT).
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OBJECTIVES: This report presents the 5-year results of the Grampian Region Early Anistreplase Trial (GREAT) and quantifies the benefit of earlier thrombolysis in terms that are generally applicable. BACKGROUND: Although it is accepted that the earlier thrombolytic therapy is given for acute myocardial infarction the greater the benefit, there are widely differing estimates of the magnitude of the time-related benefit of thrombolysis because of inappropriate trial design and analysis. METHODS: In a previously reported randomized trial, anistreplase (30 U) was given intravenously either before hospital admission or in the hospital, at a median time of 105 and 240 min, respectively, after onset of symptoms. Intention to treat and multivariate analyses of the 5-year results were performed. RESULTS: By 5 years, 41 (25%) of 163 patients had died in the prehospital treatment group compared with 53 (36%) of 148 in the hospital treatment group (log-rank test, p < 0.025). Delaying thrombolytic treatment by 1 h increases the hazard ratio of death by 20%, equivalent to the loss of 43/1,000 lives within the next 5 years (95% confidence interval 7 to 88, p = 0.012). Delaying thrombolytic treatment by 30 min reduces the average expectation of life by approximately 1 year. CONCLUSIONS: The magnitude of the benefit from earlier thrombolysis is such that giving thrombolytic therapy to patients with acute myocardial infarction should be accorded the same degree of urgency as treatment of cardiac arrest. Policies should be developed for giving thrombolytic therapy on-site if practicable and by the first qualified person to see the patient. (+info)
Audit of prehospital thrombolysis by general practitioners in peripheral practices in Grampian.
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BACKGROUND: In the Grampian region early anistreplase trial (GREAT), domiciliary thrombolysis by general practitioners was associated with a halving of one year mortality compared with hospital administration. However, after completion of the trial and publication of the results, the use of this treatment by general practitioners declined sharply. OBJECTIVE: To increase the proportion of eligible patients receiving timely thrombolytic treatment from their general practitioners. SETTING: Practices in Grampian located > or = 30 minutes' travelling time from Aberdeen Royal Infirmary, where patients with suspected acute myocardial infarction were referred after being seen by general practitioners. AUDIT STANDARD: A call-to-needle time of 90 minutes, as proposed by the British Heart Foundation (BHF). METHODS: Findings of this audit of pre-hospital management of acute myocardial infarction were periodically fed back to the participating doctors, when practice case reviews were also conducted. RESULTS: Of 414 administrations of thrombolytic treatment, 146 (35%) were given by general practitioners and 268 (65%) were deferred until after hospital admission. Median call-to-needle times were 45 (94% < or = 90) and 145 (7% < or = 90) minutes, respectively. Survival at one year was improved with prehospital compared with hospital thrombolysis (83% v 73%; p < 0.05). The proportion of patients receiving thrombolytic treatment from their general practitioners did not increase during the audit. CONCLUSIONS: In practices > or = 30 minutes from hospital, the BHF audit standard was readily achieved if general practitioners gave thrombolytic treatment, but not otherwise. Knowledge of the benefits of early thrombolysis, and feedback of audit results, did not lead to increased prehospital thrombolytic use. Additional incentives are required if general practitioners are to give thrombolytic treatment. (+info)