Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency. The GUSTO Enzyme Substudy

BACKGROUND: The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment. RESULTS: Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.     

Molecular basis of fibrinolysis, as relevant for thrombolytic therapy

The fibrinolytic system comprises an inactive proenzyme, plasminogen, that is converted by plasminogen activators to the active enzyme, plasmin, that degrades fibrin. Two physiological plasminogen activators have been identified: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Plasminogen activation for clot lysis is regulated by specific molecular interactions between tissue-type plasminogen activator (t-PA), plasminogen and fibrin, whereby the lysine-binding sites of the plasminogen molecule play a crucial role by mediating its binding to fibrin, and by controlling the inhibition rate of plasmin by alpha 2-antiplasmin. The recognition that thrombosis within the infarct related coronary artery plays a major role in the pathogenesis of acute myocardial infarction and the observation that early administration of thrombolytic agents results in recanalization of occluded coronary arteries, have provided the basis for the development of thrombolytic therapy in acute myocardial infarction. The elucidation of the biochemical mechanism of fibrin-specific plasminogen activation has fueled the hope that specific and efficacious thrombolytic agents might become available. Comparative studies between the non-fibrin-selective streptokinase and fibrin-selective recombinant t-PA (rt-PA) have shown a difference in efficacy for early coronary artery recanalization, whereas the GUSTO trial has established that clinical benefit in patients with acute myocardial infarction is indeed correlated with the rapidity and frequency of sustained recanalization and that effective thrombolysis requires adequate anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO-1) trial on the use of thrombolytics in Germany. ALKK Study Group. Arbeitsgemeinschaft der Leitenden Kardiologischen Krankenhaus?rtze

Our results show significant and independent influence of the GUSTO-1 trial on the use of recombinant tissue plasminogen activator in acute myocardial infarction in Germany. This influence started soon after the publication of the trial and was not restricted to subgroups who benefitted most from recombinant tissue plasminogen activator.     

Thrombolytic treatment in acute myocardial infarction. Choice of preparations in Norwegian hospitals

In 1994 Statens legemiddelkontroll recommended Norwegian hospitals to increase the use of recombinant tissue plasminogen activator (r-tPA) in thrombolytic treatment of acute myocardial infarction. Using a questionnaire, which was distributed to all medical departments in Norwegian hospitals, we examined and assessed the preference of thrombolytic agents. None of the coronary care units administered r-tPA routinely as their first choice. Of 59 hospitals involved, 35 (59%) considered r-tPA on a wider indication (i.e. young age, short history of symptoms, and anterior wall infarction) than the 24 (41%) that only used r-tPA when streptokinase had recently been given. Of a total of 11,191 cases of myocardial infarction in 1996, 628 (6%) were treated with r-tPA. Closer examination of 2,818 cases of myocardial infarction in 13 hospitals revealed that thrombolytic treatment was given in 1,016 (36%) instances. In 206 cases (20%), the chosen agent was r-tPA, whereas 810 (80%) were given streptokinase. The reasons for the preference of streptokinase to r-tPA are discussed.     

Update in ophthalmology (Prague, 10-13 March 1997)

The use of tissue plasminogen activator (t-PA) in the management of acute myocardial infarction, as effective thrombolytic agent, is well established. Thrombolytic therapy, limiting the extent of myocardial necrosis, reduces the infarct-related morbidity and mortality and improves the prognosis in patients with acute myocardial infarction. Thrombolytic agents present various side effects. Allergic reactions may occur with both streptokinase (ST) (or with anistreplase, the equimolecular mixture of streptokinase and human plasminogen); and t-PA. The incidence of allergic reactions associated with the use of t-PA is much lower if compared with other thrombolytic agents. Since t-PA is structurally identical to endogenous t-PA, its administration should not cause anaphylactic reactions. The purpose of this case presentation is to describe the occurrence of an anaphylactoid reaction during infusion of t-PA in a 63 year-old man, admitted to the Cardiac Care Unit (C.C.U.) with diagnosis of acute myocardial infarction.     

Cost comparison of immediate angioplasty versus thrombolysis followed by conservative therapy for acute myocardial infarction: a randomized prospective trial. Mayo Coronary Care Unit and Catheterization Laboratory Groups

OBJECTIVE: Immediate angioplasty and thrombolysis followed by conservative therapy are treatment strategies for acute myocardial infarction. The objective of this study was to compare the costs of these two strategies during a 12-month period. METHODS: Of 103 patients with acute myocardial infarction who sought medical assistance within 12 hours after onset of symptoms, 4 were excluded from analysis for various reasons, 51 received tissue plasminogen activator, and 48 underwent immediate angioplasty as the initial revascularization strategy. The main outcome determinants were direct monetary costs and indirect measures of costs, including duration of hospital stay and return to work. RESULTS: No significant difference in monetary costs between the two initial treatment strategies could be demonstrated. A trend was noted toward a briefer hospital stay and fewer late in-hospital procedures for patients treated initially with immediate angioplasty. Other measures of indirect costs were not statistically different. CONCLUSION: The hypothesis that thrombolysis followed by conservative therapy would be more cost-effective than immediate angioplasty in the treatment of patients with acute myocardial infarction could not be substantiated. The two strategies seem to have similar cost-effectiveness.     

Evaluation of drug treatment of myocardial infarction in public hospitals of Andalusia. GAUME (Andalusian Group for performance of Studies on Drug Utilization)

BACKGROUND: The management of patients with acute myocardial infarction (AMI) has changed over the last decade. The aim of this study was to evaluate the pharmacologic treatment of AMI in the clinical practice, with special emphasis in thrombolytic therapy. MATERIAL AND METHODS: Prospective drug utilization survey, collecting data from 26 hospitals belonging to the Andalusian Health Service, Spain, during one month period. Pharmacologic treatment in the first 24 h was obtained. RESULTS: Out of 379 patients recruited, 52.8% received thrombolytic therapy, although another 19% could have obtained some benefit from that therapy. Alteplase was the most frequently used thrombolytic (65.5%). The regimen prescribed was mainly that followed in GUSTO Study (45.8%) or double bolus (43.5%). In a high percentage of patients the thrombolytic selection was not made according to the results of the literature. Women and patients older than 75 years were less likely to receive thrombolytic therapy. There was a high utilization of aspirin (89.7%), nitrates (84.4%) and heparin (83.6%). CONCLUSIONS: Thrombolytic therapy was prescribed in a higher percentage of patients than is reported in other trials. In spite of that, thrombolytics should have been used in more patients. As alteplase does not have a definitive benefit over streptokinase, protocol is needed when selecting a thrombolytic agent.     

Lipid peroxidation in healthy fetuses, preterm and fullterm neonates

Thrombolytic therapy has been accepted in the treatment of acute myocardial infarction. Given historical recommendations that thrombolytic therapy is contraindicated in patients receiving CPR, its potential clinical benefit for facilitating conversion of rhythm in patients in refractory cardiac arrest has not been investigated. We present three case reports in which patients with confirmed acute myocardial infarction had a witnessed cardiac arrest in the ED. Standard Advanced Cardiac Life Support measures failed in all three cases. A bolus infusion of tissue plasminogen activator was administered during CPR in refractory ventricular fibrillation (two cases) and pulseless ventricular tachycardia (one case). Patients were given tissue plasminogen activator and had defibrillation, followed by a spontaneous return of circulation, with resuscitation and subsequent discharge. No postarrest sequelae were observed as a result of thrombolytic use during the resuscitative process. We conclude that bolus thrombolytic infusions during CPR may facilitate spontaneous return of circulation in select patients with confirmed acute myocardial infarction, witnessed cardiac arrest in the ED, and refractory ventricular fibrillation or tachycardia.     

Pharmacologic profile of survivors of acute myocardial infarction at United States academic hospitals

Optimal drug therapy for patients with acute myocardial infarction (AMI) is well described in the medical literature. However, data on the actual pharmacologic management of patients surviving AMI at academic hospitals is unavailable. The purpose of this study was to document treatment profiles in 500 patients surviving AMI at 12 academic hospitals in the United States. These profiles were compared with established guidelines and were evaluated for trends. Overall, thrombolytics (streptokinase > or = tissue-type plasminogen activator) were administered in 29% of the patients, with a greater proportion of patients receiving beta-blockers than calcium channel antagonists in the initial 72 hours (61% vs 40%; p < 0.005) and at discharge (51% vs 35%; p < 0.005). Further, women were less likely than men to receive thrombolytic therapy (odds ratio [OR] = 0.61; confidence interval [CI], 0.54 to 0.69) or beta-blocker therapy within the first 72 hours (OR = 0.61; CI, 0.55 to 0.67) or at hospital discharge (OR = 0.53; CI, 0.48 to 0.58). Overall, improvements could still be made in the number of patients who receive thrombolytic and acute and chronic beta-blocker therapies after AMI, particularly in women. Changes in treatment profiles may be a reflection of the publication of large clinical trials.     

Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.     

The absence of a procoagulant effect after TNK-t-PA: a comparison with streptokinase and rt-PA

A limitation of current fibrinolytic drugs is the procoagulant activity induced by their administration. TNK is a mutant of tissue plasminogen activator (t-PA) with high fibrin specificity, resistance to plasminogen activator inhibitor-1 and slow plasma clearance, which is administered in a single intravenous bolus. In this study we investigated the procoagulant effect of TNK-t-PA compared to streptokinase, rt-PA or no thrombolysis. Twenty-nine patients with acute myocardial infarction, treated within 6 hours of symptom onset with 1.5 MU streptokinase over 1 hour (n = 12), 100 mg rt-PA in 1.5 hours (n = 12) or 30-40 mg TNK-t-PA in 15 s (n = 5), were studied and compared to 7 patients with contraindications to thrombolysis (control group). All patients received a similar i.v. heparin regimen for at least 24 hours. Blood samples were drawn before the start of treatment (time 0) and after 2 hours. Thrombin formation was assessed as plasma concentrations of thrombin-antithrombin complex (TAT). The four patient groups did not differ significantly in age, sex, time to treatment, infarct location, and TAT values at time 0 (mean value +/- standard error of the mean 9 +/- 2 micrograms/l). Mean TAT levels at 2 hours were 26 +/- 6 micrograms/l in streptokinase treated patients (p = 0.005 vs time 0), 21 +/- 4 micrograms/l in rt-PA treated patients (p < 0.05 vs time 0), 5 +/- 0.6 micrograms/l in TNK treated patients, and 4 +/- 0.4 micrograms/l in controls (NS vs time 0 for TNK and controls). In conclusion, our data suggest that, in patients with acute myocardial infarction, bolus TNK-t-PA, unlike streptokinase or rt-PA infusions, is devoid of procoagulant effects, evaluated 2 hours after its administration.     

Pronounced differences between the native K+ channels and KAT1 and KST1 alpha-subunit homomers of guard cells

BACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in approximately 30 000 US patients each year. This number is expected to rise with the increasing use of thrombolytic therapy for MI. However, no data exist for the economic effect of stroke in the setting of acute MI (AMI). The purpose of this prospective study was to assess the effect of stroke on medical resource use and costs in AMI patients in the United States. METHODS AND RESULTS: Medical resource use and cost data were prospectively collected for 2566 randomly selected US GUSTO I patients (from 23 105 patients) and for the 321 US GUSTO I patients who developed non-bypass surgery-related stroke during the baseline hospitalization. Follow-up was for 1 year. All costs are expressed in 1993 US dollars. During the baseline hospitalization, stroke was associated with a reduction in cardiac procedure rates and an increase in length of stay, despite a hospital mortality rate of 37%. Together with stroke-related procedural costs of $2220 per patient, the baseline medical costs increased by 44% ($29 242 versus $20 301, P<0.0001). Follow-up medical costs were substantially higher for stroke survivors ($22 400 versus $5282, P<0.0001), dominated by the cost of institutional care. The main determinant for institutional care was discharge disability status. The cumulative 1-year medical costs for stroke patients were $15 092 higher than for no-stroke patients. Hemorrhagic stroke patients had a much higher hospital mortality rate than non-hemorrhagic stroke patients (53% versus 15%, P<0.001), which was associated with approximately $7200 lower mean baseline hospitalization cost. At discharge, hemorrhagic stroke patients were more likely to be disabled (68% versus 46%, P=0.002). CONCLUSIONS: In this first large prospective economic study of stroke in AMI patients, we found that strokes were associated with a 60% ($15 092) increase in cumulative 1-year medical costs. Baseline hospitalization costs were 44% higher because of longer mean lengths of stay. Stroke type was a key determinant of baseline cost. Follow-up costs were more than quadrupled for stroke survivors because of the need for institutional care. Disability level was the main determinant of institutional care and thus of follow-up costs.     

Cost-effectiveness of thrombolytic therapy for acute myocardial infarction

OBJECTIVE: To estimate the cost-effectiveness of thrombolytic therapy versus no thrombolytic therapy for patients following acute myocardial infarction, focusing on the impact of time to treatment on outcome. METHODS: A decision model was developed to assess the benefits, risks, and costs associated with thrombolytic therapy for treatment of acute myocardial infarction compared with standard nonthrombolytic therapy. The model used pooled data from a recent study of nine large randomized, controlled clinical trials and 12-month outcome data from a recently published meta-analysis of thrombolytic therapy trial data. Outcomes were expressed in terms of survival to hospital discharge and survival to 1 year after discharge. The risks of treatment that led to death, morbidity, or added costs were estimated. The model determined excess and marginal costs per death averted to hospital discharge and at 1 year. Results were also estimated in terms of cost per year of life saved. Sensitivity analyses included variations in time to treatment and drug cost. RESULTS: The marginal cost of thrombolytic therapy per death averted at 1 year was $222,344, or $14,438 per year of life saved. For patients treated within 6 hours of acute myocardial infarction, the marginal cost per death averted was $181,536 at 1 year, or $11,788 per year of life saved. CONCLUSIONS: Thrombolytic therapy is significantly more cost-effective than many other cardiovascular interventions and compares favorably with other forms of medical therapy. Results suggest that shortening the time to treatment has a critical impact on the cost-effectiveness of thrombolytic therapy.     

Fibrinolysis or angioplasty in acute myocardial infarction?

Early reperfusion during myocardial infarction limits myocardial injury and reduces mortality. Fibrinolysis (with streptokinase, or tissue or recombinant plasminogen activators) is today an established method for the treatment of myocardial infarction patients manifesting ST-segment elevation or left bundle branch block at ECG (electrocardiography), effective reperfusion being obtained in fifty per cent of cases. Extensive developments are under way, both of fibrinolytic substances and of various adjuvant treatments. A satisfactory alternative treatment to fibrinolysis is percutaneous transluminal coronary angioplasty (PTCA), a method which can be used when fibrinolysis is contraindicated or during cardiogenic shock, or when there is no sign of reperfusion in response to fibrinolytic treatment. Provided the facilities and competence are available, PTCA can even be used as primary treatment instead of fibrinolysis.     

Atheroembolic disease following administration of tissue plasminogen activator (TPA)

Atheroembolic disease is an uncommon condition with many interesting manifestations and has been reported following various procedures. Its occurrence following thrombolytic therapy is extremely rare, with only a few case reports in the literature. However, with a widespread application of thrombolysis in patients with acute myocardial infarction, its incidence is likely to increase and therefore this entity needs to be recognized. Early recognition of the illness may help avoid further expensive and unnecessary investigations. We report two cases of atheroembolic disease following the administration of human recombinant tissue plasminogen activator (TPA).     

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarction is reperfusion of the infarct-related coronary artery. Duteplase is a double-chain recombinant tissue-type plasminogen activator. Its efficacy and safety were evaluated in patients with acute myocardial infarction treated within 4 h of onset of chest pain in this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase 0.6 MU.kg-1 over 4 h, with concomitant oral aspirin and intravenous heparin. Coronary arteriography was performed at 60 min, 90 min and approximately 24 h after the start of duteplase infusion to assess the perfusion grade (TIMI scoring) of the infarct-related coronary artery. Safety was assessed by monitoring patients closely for bleeding and for all other adverse experiences during the 72-h study period. Reinfarction during the study period was also recorded, and deaths at any time during the period in hospital were documented. TIMI grade 2 or 3 patency of the infarct-related coronary artery at 90 min was achieved in 70% of the patients and 7% of these "patent' infarct-related coronary arteries had reoccluded by 20 to 36 h. Clinical reinfarction during the 72-h study period was observed in 7%. Total in-hospital mortality was 8%. Serious or life-threatening bleeding occurred in 4% of the patients. There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirin and intravenous heparin, in acute myocardial infarction resulted in patency of the infarct-related coronary artery and a safety profile comparable to those reported for the other form of tissue-type plasminogen activator, alteplase. However, there remains a problem with reocclusion and reinfarction after initially successful thrombolysis.     

Thrombolytic therapy in ischemic infarct

Thrombolytic therapy in acute ischemic stroke is safe and effective in a defined subgroup of stroke patients. Until now, different fibrinolytic substances including urokinase, streptokinase and recombinant tissue plasminogen activator (rt-PA) have been tested regarding safety, efficacy, dosage and economic parameters in patients suffering from both carotid and basilar artery territory strokes. Recently, two large multicenter placebo-controlled intravenous rt-PA studies were published. The results show that thrombolysis of acute carotid territory strokes (European Cooperative Acute Stroke Study) and of strokes with a deficit measurable on the NIH Stroke Scale (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study) improves clinical and economic outcome parameters in patients who were treated within 6 hours of the onset of symptoms and had that no signs of extended early infarction on the initial CT-scan. The occurrence of intracranial hemorrhages is more frequent after thombolytic therapy, but the majority of bleeding complications referred to petechial or more confluent hemorrhage limited to the infarcted tissue, without clinical deterioration. However, the identification of the appropriate patients is difficult and depends on the level of clinical and diagnostic experience. In vertebrobasilar artery territory stroke, local intraarterial thrombolysis with urokinase or streptokinase is performed in most cases. Thrombolytic treatment within twelve hours of the onset of symptoms was associated with significantly better results concerning both survival and neurological recovery.     

Choroidal hemorrhage associated with systemic tissue plasminogen activator

PURPOSE: To determine the cause of spontaneous choroidal hemorrhage in a 67-year-old man after a myocardial infarction and administration of tissue plasminogen activator. METHODS: The patient underwent ocular examination. RESULTS: The patient retained excellent visual acuity and the choroidal hemorrhage resolved completely within two months. CONCLUSION: The administration of tissue plasminogen activator was responsible for the large extent of hemorrhage and should be considered in the differential diagnosis of hemorrhagic choroidal detachment.     

ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group

OBJECTIVE: To assess effects of intravenous streptokinase, one month of oral aspirin, or both, on long term survival after suspected acute myocardial infarction. DESIGN: Randomised, "2 x 2 factorial," placebo controlled trial. SETTING: 417 hospitals in 16 countries. SUBJECTS: 17 187 patients with suspected acute myocardial infarction randomised between March 1985 and December 1987. Follow up of vital status complete to at least 1 January 1990 for 95% of all patients and to mid-1997 for the 6213 patients in United Kingdom. INTERVENTIONS: Intravenous streptokinase (1.5 MU in 1 hour) and oral aspirin (162 mg daily for 1 month) versus matching placebos. MAIN OUTCOME MEASURES: Mortality from all causes during up to 10 years' follow up, with subgroup analyses based on 4 year follow up. RESULTS: After randomisation, 1841 deaths were recorded in days 0-35, 991 from day 36 to end of year 1, 1478 in years 2-4, and 1230 in years 5-10. Allocation to streptokinase was associated with 29 (95% confidence interval 20 to 38) fewer deaths per 1000 patients during days 0-35. This early benefit persisted (death rate ratio 0.98 (0.92 to 1.04) for additional deaths between day 36 and end of year 10), so that there were 28 (14 to 42) and 23 (2 to 44) fewer deaths per 1000 patients treated with streptokinase after 4 years and 10 years respectively. There was no evidence that absolute survival benefit increased with prolonged follow up among any category of patient, including those presenting early after symptoms started or with anterior ST elevation. Nor did the early benefits seem to be lost in any category (including those aged over 70). Allocation to one month of aspirin was associated with 26 (16 to 35) fewer deaths per 1000 during first 35 days, with little further benefit or loss during subsequent years (death rate ratio 0.99 (0.93 to 1.06) between day 36 and end of year 10). The early benefit obtained with combination of streptokinase and one month of aspirin also seemed to persist long term. CONCLUSIONS: The early survival advantages produced by fibrinolytic therapy and one month of aspirin started in acute myocardial infarction seem to be maintained for at least 10 years.     

Regional variation across the United States in the management of acute myocardial infarction. GUSTO-1 Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries

BACKGROUND: Differences in the management of acute myocardial infarction have been reported among countries, but few studies have investigated this issue in regions of the United States. METHODS: We compared the management of acute myocardial infarction among census regions across the United States, using data from the first Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-1) comprising 21,772 patients, and from the American Hospital Association. RESULTS: We found substantial regional variation in the management of acute myocardial infarction in the United States. Beta-blockers (prescribed for a range of 55 to 81 percent of patients in the various regions), nitrates (prescribed for 61 to 77 percent), and angiotensin-converting-enzyme inhibitors (prescribed for 18 to 23 percent) were used most often in New England, whereas calcium-channel blockers (31 to 42 percent) and lidocaine (14 to 43 percent) were used least often there. Similarly, the proportion of patients undergoing various cardiac procedures differed among regions (range for angiography, 52 to 81 percent of patients; angioplasty, 22 to 35 percent; and coronary-artery bypass surgery, 9 to 17 percent) and was lowest in New England. The regional use of cardiac procedures was closely related to their availability, except in New England. After the analysis was adjusted for clinical and hospital variables, patients in New England were found to be less likely to undergo angiography than patients in the other regions (odds ratio, 0.37; 95 percent confidence interval, 0.32 to 0.42). There was no apparent relation between the use of cardiac procedures and rates of recurrent infarction or death at 30 days or 1 year. CONCLUSIONS: There is substantial regional variation in the use of cardiac medications and procedures to manage acute myocardial infarction in the United States. The use and availability of cardiac procedures are closely related. The management of acute myocardial infarction in New England is atypical in that the relatively limited availability of cardiac procedures does not account for their relatively low use in that region.