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Biomedical subjects

M L Simoons

Publications and source records attributed to M L Simoons.

At least 37 records · Page 2Linked to original sources

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.

Humans

Mortality, reinfarction, left ventricular ejection fraction and costs following reperfusion therapies for acute myocardial infarction.

The comparative efficacy of thrombolytic drugs and primary angioplasty for acute myocardial infarction have recently been studied, but long-term follow-up data have not yet been reported. We conducted a randomized trial involving 301 patients with acute myocardial infarction; 152 patients were randomized to primary angioplasty and 149 to intravenous streptokinase. Left ventricular function was assessed with a radionuclide technique both at hospital discharge and at the end of the follow-up period. Follow-up data were collected after a mean (+/-SD) of 31 +/- 9 months. Total medical costs were calculated. At the end of the follow-up period, 5% of the angioplasty patients had died from a cardiac cause compared to 11% of the patients randomized to intravenous streptokinase, P = 0.031. Cardiac death or a non-fatal reinfarction occurred in 7% of angioplasty patients compared to 28% of streptokinase patients, P < 0.001. There was a sustained benefit of angioplasty compared to streptokinase on left ventricular function. The total medical costs in the two groups were similar. Coronary anatomy (patency and single or multivessel disease), infarct location and previous myocardial infarction were important determinants of clinical outcome and costs. After 31 +/- 9 months of follow-up, primary angioplasty compared to intravenous streptokinase results in a lower rate of cardiac death and reinfarction, a better left ventricular ejection fraction, and no increase in total medical costs.

Aged

Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial.

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79-100%) in patients with extensive ST segment elevation (> or = 400 microV), if both speed of ST recovery and extent of ST segment elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems. We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended.

Arteries

Ridogrel as an adjunct to thrombolysis in acute myocardial infarction.

An open pilot study was performed to assess the safety and preliminary efficacy of ridogrel, a selective thromboxane-A2 synthetase inhibitor and thromboxane-A2/prostaglandin endoperoxide receptor blocker, as adjunct to thrombolysis, with alteplase and heparin. In 50 patients with acute myocardial infarction, 300 mg ridogrel was injected intravenously in addition to alteplase and heparin. Ridogrel was continued orally (300 mg) twice daily for 5 days. Patency rate at initial (90 min) angiography, defined as thrombolysis in myocardial infarction perfusion grades 2 or 3, was 86%. Rescue percutaneous transluminal coronary angioplasty was performed in 10 patients; immediate results were good in nine, while a large dissection occurred in one patient. New ischemia occurred in 10 patients within 24 h, and after the second angiogram in seven cases. Three underwent coronary artery bypass grafting and seven percutaneous transluminal coronary angioplasty without further complication. Patency rate at second angiography (between 6 and 24 h) was 94%. New Q-waves appeared in 56% of the patients; 36% had a non-Q-wave infarction and 8% had no enzyme rise. Enzymatic infarct size, estimated by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase released in 72 h, was substantially smaller than in comparable studies with rt-PA and heparin. One patient died due to a cerebrovascular hemorrhage. No other deaths occurred. Bleeding complications were seen in 18 patients (36%), necessitating blood transfusion in three. Reinfarction did not occur. Eventually 49 patients were discharged in good condition. Safety with regard to bleeding complications of ridogrel in conjunction with alteplase is about the same as that of aspirin. Immediate and late patency rates were high. Rescue percutaneous transluminal coronary angioplasty could be performed with relative safety and early reocclusion could be successfully dealt with by repeat percutaneous transluminal coronary angioplasty. Further studies with this or similar compounds seem warranted.

Adult

Stroke after thrombolysis. Mortality and functional outcomes in the GUSTO-I trial. Global Use of Strategies to Open Occluded Coronary Arteries.

BACKGROUND: Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial. METHODS AND RESULTS: Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Over-all, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy (P = .007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy (P < .001). Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling, with no significant treatment-related differences. Stroke subtype affected prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions. Patients with moderate or severe residual deficits showed significantly decreased quality of life. Advanced age, lower weight, prior cerebrovascular disease or hypertension, systolic and diastolic blood pressures, randomization to tissue plasminogen activator, and an interaction between age and hypertension were significant predictors of intracranial hemorrhage. CONCLUSIONS: Stroke remains a rare but catastrophic complication of thrombolysis. Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups, particularly the elderly and patients with prior cerebrovascular events.

Aged

Benefit of thrombolytic therapy is sustained throughout five years and is related to TIMI perfusion grade 3 but not grade 2 flow at discharge. The European Cooperative Study Group.

BACKGROUND: Long-term follow-up in patients treated with thrombolysis for acute myocardial infarction thus far has been reported in a few studies only, and no long-term follow-up is available for patients who underwent additional percutaneous transluminal coronary angioplasty (PTCA). This report describes 5-year survival as collected in patients who received placebo, recombinant tissue plasminogen activator (rTPA), or rTPA with additional immediate PTCA in two European Cooperative Study Group trials. Determinants for long-term survival were assessed in 1043 patients discharged alive. METHODS AND RESULTS: Five-year follow-up information on mortality was collected. Hospital mortality was lower after rTPA than placebo (2.5% versus 5.7%, P = .04) and higher after rTPA with immediate PTCA compared with rTPA without additional intervention (6.0% versus 2.2%, P = .07). Of the 1043 hospital survivors, data were available for 923 patients, of whom 109 died. In the placebo group, mortality after hospital discharge was 10.7% versus 11.0% in the comparative rTPA group. The patients treated with rTPA and immediate PTCA had a mortality rate of 10.5% versus 8.9% in the rTPA group without PTCA (all P = NS). Significant determinants of mortality in multivariate proportional hazards analysis were enzymatic infarct size, indicators of residual left ventricular function, number of diseased vessels and TIMI perfusion grade at discharge. Patients with TIMI grade 2 flow had mortality rates similar to those with TIMI flow grades 0 and 1, while prognosis was better in patients with TIMI flow grade 3. CONCLUSIONS: The initial in-hospital benefit of thrombolysis with intravenous rTPA is maintained throughout 5 years, with no early or late beneficial effect of systematic immediate PTCA. Enzymatic infarct size, left ventricular function, and extent of coronary artery disease are predictors for long-term survival. TIMI perfusion grade 2 at discharge should be considered as an inadequate result of therapy.

Angioplasty, Balloon, Coronary

Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective. METHODS: Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment. RESULTS: One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study. CONCLUSIONS: The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Adult

Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators.

BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92. CONCLUSIONS: The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy.

Coronary Angiography

Incidence and follow-up of Braunwald subgroups in unstable angina pectoris.

OBJECTIVES: This study was performed to establish the prognosis of patients with unstable angina within the subgroups of the Braunwald classification. BACKGROUND: Among many classifications of unstable angina, the Braunwald classification is frequently used. However, the incidence and risk for each subgroup in clinical practice have not been established. METHODS: Prospective data for 417 consecutive patients admitted for suspected unstable angina were analyzed. Patients were classified according to Braunwald criteria and followed up for 6 months. Survival, infarct-free survival and infarct-free survival without intervention are reported for each class. RESULTS: After in-hospital observation the final diagnosis was acute myocardial infarction in 26 patients (6%), noncoronary chest pain in 109 (26%) and definite unstable angina in 282 (68%). Recurrence of chest pain was significantly different for the different severity classes (28%, 45% and 64% for classes I [accelerated angina], II [subacute angina at rest] and III [acute angina at rest], respectively) but not for clinical circumstances (49% and 53% for classes B [primary unstable angina] and C [postinfarction unstable angina], respectively). Six-month and infarct-free survival (96% and 88%, respectively) were not significantly different between severity classes but were significantly different (p = 0.01) between classes B (97% and 89%) and C (89% and 80%). Infarct-free survival without intervention was best for class II (72%), intermediate for class I (53%) and worst for class III (35%). In multivariate analysis, elderly age, male gender, hypertension, class C and maximal (intravenous) therapy were independent predictors for death; elderly age and class C for infarct-free survival; and male gender, class III, class C, electrocardiographic changes and maximal therapy were associated with infarct-free survival without intervention. CONCLUSIONS: Braunwald classification is an appropriate instrument to predict outcome. Risk stratification by these criteria provides a tool for patient selection in clinical trials and for evaluation of treatment strategies.

Aged

Noninvasive assessment of speed and stability of infarct-related artery reperfusion: results of the GUSTO ST segment monitoring study. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: The ST segment monitoring substudy of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial compared the speed and stability of ST segment recovery among four thrombolytic strategies for acute myocardial infarction. BACKGROUND: Rapid resolution of ST segment elevation has been suggested as a noninvasive marker of infarct-related artery patency. We expected that patients treated with accelerated recombinant tissue-type plasminogen activator (rt-PA) would show a quicker recovery than that of other patients but that those treated with streptokinase would show greater stability of recovery. METHODS: ST segment monitoring was initiated in 1,067 patients within 30 min of the start of thrombolysis and continued for > 18 h with the use of a three-channel continuous vectorcardiographic monitor, a 12-lead continuous electrocardiographic (ECG) monitor or a three-channel (V2, V5, aVF) Holter ambulatory ECG monitor. RESULTS: Time to 50% recovery could be assessed in 618 patients and was similar in the four treatment groups: median 45 min with streptokinase/subcutaneous heparin, 45 min with streptokinse/intravenous heparin, 42 min with accelerated rt-PA and 47 min with combination therapy (p = 0.7). No significant difference among the thrombolytic regimens was shown with the three monitors used. Time to initiation of ST segment analysis was directly related to time to 50% recovery (p = 0.0001) and was its best predictor in a multiple regression model. ST segment elevation recurred equally in each treatment group (approximately 36%, p = 0.9) but was significantly more common in patients with a patent infarct-related artery (p = 0.033) or a low ejection fraction (p = 0.001). CONCLUSIONS: The greater 90-min patency seen with accelerated rt-PA in the angiographic substudy did not correlate with a shorter time to 50% ST segment recovery, possibly because of technical limitations and study design. The similar rates of recurrent ischemia (as assessed by ST elevation) among the regimens support the similar infarction and reocclusion rates seen in the main trial and angiographic substudy.

Drug Therapy, Combination

Antiplatelet therapy in therapy-resistant unstable angina. A pilot study with REO PRO (c7E3).

Patients with unstable angina, refractory to intensive medical therapy, are at high risk of developing thrombotic complications, such as myocardial infarction and coronary occlusion during coronary angioplasty. As platelet aggregation and thrombus formation play an important role in this ongoing ischaemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) has been designed to modify the clinical course and underlying coronary lesion morphology. To evaluate whether c7E3 could influence the incidence of complications, we randomized 60 patients to c7E3 or placebo after initial angiography had demonstrated a culprit lesion amenable for angioplasty. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite intensive medical therapy. After study drug bolus and infusion, angiography was repeated and angioplasty performed. Recurrent ischaemia during study drug infusion occurred in nine and 16 patients from the c7E3 and placebo groups, respectively (P = 0.06). Major events defined as death, myocardial infarction or urgent intervention occurred in one and seven patients, respectively (P = 0.03). One patient from the placebo group died as a result of recurrent infarction. Resolution of clots was only observed in the c7E3 group, combined with improvement in TIMI flow grade in 20% of patients. Quantitative angiography showed an improvement in percentage diameter stenosis in the c7E3 group, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. No excess bleeding was observed in the treatment group. Thus, c7E3 bolus and infusion, combined with heparin and aspirin improved the clinical course, the coronary lesion morphology and rheology in patients with unstable angina, refractory to medical treatment.

Abciximab

Costs and effects of c7E3 in high risk PTCA patients. An indirect analysis for The Netherlands.

A cost effectiveness study is presented on the use of c7E3 in high risk patients undergoing percutaneous coronary angioplasty (PTCA). The results from the EPIC study have been combined with cost data from The Netherlands. The study took account of the number of survivors without ischaemic events, and the number with neither ischaemic events nor bleeding (both measured after 6 months). It is estimated that the initial costs of c7E3 and the additional costs due to the increased risk of bleeding are almost entirely counterbalanced by the savings, as a result of fewer myocardial infarctions and revascularizations. The additional costs per additional patient without ischaemic events are approximately DFL 5235. The additional costs per additional patient with neither ischaemic events nor bleeding are estimated at DFL 15,685. Both figures are less than the average for similar procedures without c7E3. Sensitivity analysis supports the conclusion that c7E3 treatment is efficient. However, cost effectiveness could be further improved if patients are carefully selected.

Abciximab

Thrombolytic therapy for evolving myocardial infarction needs an approach that integrates benefit and risk.

Thrombolytic therapy is a major step forward in the treatment of acute myocardial infarction and results in substantial reduction of mortality. However, in individual patients the benefits and bleeding risk are difficult to estimate, especially when benefit seems small or outweighed by the risk of intracranial bleeding. For this and other reasons less than half the patients with evolving myocardial infarction are treated with thrombolytic therapy. We propose to approach the decision 'to treat or not to treat' in a systematic way, integrating estimated benefit and intracranial bleeding risk in individual patients. According to a decision-model developed with currently available medical knowledge, thrombolytic therapy appears beneficial in the majority of patients with evolving myocardial infarction provided that ST segment elevation is present and treatment can be started within 12 h of onset of symptoms. Thrombolytic therapy is warranted in the absence of risk factors for intracranial haemorrhage, even if the risk of cardiac death in the first year without thrombolytic therapy is as low as 2.3% (patients with small inferior wall infarctions). For patients with increased intracranial bleeding risk, the cardiac baseline risk without thrombolytic therapy and treatment delay become important variables to take into account when selecting thrombolytic therapy. Precise thresholds for these variables are presented.

Cerebral Hemorrhage

Pre-hospital thrombolytic therapy with either alteplase or streptokinase. Practical applications, complications and long-term results in 529 patients.

OBJECTIVE: To assess the practical application, safety and long-term outcome of pre-hospital thrombolytic intervention with either alteplase or streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presenting within 6 h of symptom onset and with electrocardiographic evidence of extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioner or the ambulance nurse using a standardized questionnaire with (contra-) indications for thrombolytic therapy. Computerized ECG was recorded by ambulance nurses. In the presence of extensive ST segment elevation (sum ST deviation of at least 1.0 mV), eligible patients received either 100 mg alteplase (n = 246) or 50 mg alteplase in the ambulance followed by 0.75 x 10(6) IE streptokinase in hospital (n = 90), or 1.5 x 10(6) IE streptokinase intravenously (n = 193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation, cardiac arrest) and side effects (hypotension, allergic reactions) during transportation to hospital and in the first 24 h following hospitalization, and survival up to 5 years follow-up. RESULTS: From 1988-1993, 529 patients received thrombolytic treatment initiated pre-hospital. The time gained by pre-hospital administration of thrombolysis amounted to 50 min. The rate of complications during transportation and during the first 24 h after hospitalization was low. Hospital mortality was 2% and 1-year mortality 3%. Cumulative survival at 5 years was 92%. This was superior to the 84% 5-year survival observed in a matched group of 239 patients with similar baseline characteristics treated with alteplase in hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinase is feasible and safe and results in significant time gain. The long-term prognosis is excellent in spite of extensive evolving myocardial infarction upon admission.

Adult

Pre-hospital triage of patients with suspected myocardial infarction. Evaluation of previously developed algorithms and new proposals.

OBJECTIVE: To evaluate previously developed algorithms for the improvement of pre-hospital triage of patients with suspected acute cardiac disease. DESIGN: Prospective study. SUBJECTS: Patients with symptoms of possible cardiac origin, who were seen by a general practitioner and subsequently referred to hospital in the municipality of Rotterdam. METHODS: Prior to hospital admission, patients with suspected acute coronary disease recorded their symptoms by standardized questionnaire and a computerized ECG was made. All patients were hospitalized and a final diagnosis was established. Algorithms proposed by other investigators to distinguish patients with, from those without, acute cardiac disease were tested. MAIN OUTCOME: Identification of patients whose likelihood for acute cardiac pathology was low (stable angina, atypical chest pain, other pathology) or high (myocardial infarction, unstable angina). RESULTS: A total of 1005 patients were studied. Forty-two percent had myocardial infarction or unstable angina pectoris. Evaluation of previously developed algorithms showed that their diagnostic accuracy was poor in the pre-hospital setting. In a separate multivariate analysis, six characteristics from the clinical history and an electrocardiogram appeared to be independently and significantly associated with acute cardiac pathology. The presence of an abnormal ECG proved to be the most important predictor. CONCLUSIONS: The hospital-based algorithms were unsuitable as a predictor for pre-hospital acute cardiac pathology. A new practical hospital admission model was developed, based on six clinical predictors, including analysis of an electrocardiogram. Following appropriate validation, this out-of-hospital protocol may lead to better triage decisions by the general practitioner.

Adult