[Guideline 'Cardiovascular Risk Management']. / Richtlijn 'cardiovasculair risicomanagement'.

The aim of the clinical practice guideline 'Cardiovascular risk management' is an integral approach to all relevant risk factors for cardiovascular disease (CVD) caused by atherothrombosis. Patients with CVD, diabetes mellitus type 2 (DM2), elevated blood pressure or cholesterol, men of 50 years or older who smoke and women of 55 years or older who smoke are eligible for assessment of relevant risk factors for CVD. All high-risk patients should receive lifestyle counselling. In patients with CVD the use of acetylsalicylic acid and often, depending on the specific disease, a beta-blocker or an angiotensin converting enzyme (ACE) inhibitor are recommended. The use of a statin is recommended if the LDL-cholesterol concentration is > or = 2.5 mmol/l. In patients with DM2, the use of statins is recommended if LDL-cholesterol is > or = 2.5 mmol/l and use of a blood pressure lowering drug with a systolic blood pressure > or = 140 mmHg, as well as glucose lowering drugs. In patients without CVD and DM2, the need for drug treatment will be determined by estimation of the absolute 10-year mortality risk of CVD. Treatment is recommended if this risk exceeds 10%. The treatment and follow-up plan will be determined individually, depending on the risk profile, morbidity, comorbidity and patient's preferences.

Logistics and quality control for DNA sampling in large multicenter studies.

To study associations between genetic variation and disease, large bio-banks need to be created in multicenter studies. Therefore, we studied the effects of storage time and temperature on DNA quality and quantity in a simulation experiment with storage up to 28 days frozen, at 4 degrees C and at room temperature. In the simulation experiment, the conditions did not influence the amount or quality of DNA to an unsatisfactory level. However, the amount of extracted DNA was decreased in frozen samples and in samples that were stored for > 7 days at room temperature. In a sample of patients from 24 countries of the EUROPA trial obtained by mail with transport times up to 1 month DNA yield and quality were adequate. From these results we conclude that transport of non-frozen blood by ordinary mail is usable and practical for DNA isolation for polymerase chain reaction in clinical and epidemiological studies.

Variability in abciximab (ReoPro) prescribing: evidence based or budget driven?

PURPOSE: Abciximab improves outcomes in patients undergoing percutaneous transluminal coronary intervention (PTCA). Clinicians, however, have expressed concerns that they do not have enough budget to administer abciximab to all eligible patients. We studied the patterns of prescribing of abciximab and identified factors that correlate with the level of usage. METHODS: In each of all 13 Dutch PTCA centres one opinion-leading cardiologist was approached to provide data on the abciximab prescribing in their centre and to co-operate in an interview on this topic. We performed linear regression analysis in which the level of abciximab prescribing was the dependent variable. Potential determinants investigated were the number of PTCAs performed, the criteria for abciximab prescribing, funding and possible financial restrictions, participation in clinical trials in the past, percentage stenting, and desired level of abciximab prescribing. RESULTS: All 13 PTCA centres in the Netherlands participated in our study. The level of abciximab prescribing varied from 2 to 36% of all PTCAs. The criteria for patient selection significantly differed between centres. Together budget, investigatorship, size, and type of the institution were highly predictive for the level of abciximab prescribing (R2 = 0.93, p < 0.001). The more patients doctors had included in clinical trials in the past, the higher was the likelihood that they had prescribed abciximab. CONCLUSIONS: Shortly after its introduction, patterns of abciximab prescribing varied widely between PTCA centres. There was no agreement on which patients to select for this preventive treatment. Budget and involvement in clinical trials in the past were important predictors of the level of prescribing in each centre.

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

AIMS: To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. METHODS AND RESULTS: Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. CONCLUSIONS: Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use.

Cost-effectiveness of HMG coenzyme reductase inhibitors; whom to treat?

AIMS: Treatment guidelines have been developed for both "primary" and "secondary" prevention of coronary heart disease. These should consider both the efficacy as well as the costs of such treatment, particularly the costs of treatment with HMG co-enzyme A reductase inhibitors (statins). In the context of guideline development in The Netherlands, the cost effectiveness of treatment with statins was analysed. METHODS: Following a modelling approach, cost effectiveness was analysed as a function of a patient's initial risk for new coronary heart disease events, combining results from 4S, CARE, LIPID, WOSCOPS and AFCAPS with Dutch cost data. For each sex and age group, an estimate was made of the level of cardiovascular risks that might correspond to a cost-effectiveness ratio under NLG 40 000 (Euro 18 151) per life year gained. RESULTS: If the 10-year risk of myocardial infarction, stroke or cardiovascular death was estimated at 9% (AFCAPS/TexCAPS), 20% (WOSCOPS), 36% (CARE) 36% (LIPID) and 47% (4S), cost effectiveness was estimated at Euro 51 400, Euro 26 013, Euro 9970, Euro 8028 and Euro 6695. The arbitrary threshold of NLG 40 000 (approximately Euro 18 000) was achieved at a 10 year coronary heart disease event risk ranging from 19% to 26% for different age groups. Assuming the effectiveness of statin treatment decreased with age, a 10-year risk, corresponding to Euro 18 000, varied from 11% (under age 30) to 41% (over age 80). Patients at higher risk levels should be considered for statin therapy. CONCLUSIONS: Treatment costs for primary or secondary prevention are determined predominantly by the costs of statin drugs. The developed model allows comparison of cost effectiveness of statin therapy across a wide range of subjects with or without coronary heart disease. The consensus committee in the Netherlands postulated that drug therapy should be considered in subjects with or without coronary heart disease in which cost-effectiveness is similar. Such groups can be identified using the presented model. When cost effectiveness ratios up to Euro 18 000 per life year gained are deemed acceptable, statin treatment should be considered in most patients with known cardiovascular disease (secondary prevention), and in a limited group of subjects who are at high risk of developing coronary heart disease (primary prevention).

Assessment of coronary reperfusion in patients with myocardial infarction using fatty acid binding protein concentrations in plasma.

OBJECTIVE: To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes. DESIGN: Retrospective substudy of the GUSTO trial. SETTING: 10 hospitals in four European countries. PATIENTS: 115 patients were treated with thrombolytic agents within six hours after the onset of acute myocardial infarction. Patency of the infarct related artery was determined by angiography within 120 minutes of the start of thrombolysis. MAIN OUTCOME MEASURES: First hour rate of increase in plasma FABP concentration after thrombolytic treatment, compared with increase in plasma myoglobin concentration and creatine kinase isoenzyme MB (CK-MB) activity. Infarct size was estimated from the cumulative release of the enzyme alpha hydroxybutyrate dehydrogenase in plasma during 72 hours, or from the sum of ST segment elevations on admission. Logistic regression analyses were performed to construct predictive models for patency. RESULTS: Complete reperfusion (TIMI 3) occurred in 50 patients, partial reperfusion (TIMI 2) in 36, and no reperfusion (TIMI 0+1) in 29. Receiver operating characteristic (ROC) curve analyses showed that the best performance of FABP was obtained when TIMI scores 2 and 3 were grouped and compared with TIMI score 0+1. The performance of FABP as a reperfusion marker was improved by combining it with alpha hydroxybutyrate dehydrogenase infarct size, but not with an early surrogate of infarct size (ST segment elevation on admission). In combination with infarct size FABP performed as well as myoglobin (areas under the ROC curve 0.868 and 0.857, respectively) and better than CK-MB (area = 0.796). At optimum cut off levels, positive predictive values were 97% for FABP, 95% for myoglobin, and 89% for CK-MB (without infarct size, 87%, 88%, and 87%, respectively), and negative predictive values were 55%, 52%, and 50%, respectively (without infarct size, 44%, 42%, and 34%). CONCLUSIONS: FABP and myoglobin perform equally well as reperfusion markers, and successful reperfusion can be assessed, with positive predictive values of 87% and 88%, or even 97% and 95% when infarct size is also taken into account. However, identification of non-reperfused patients remains a problem, as negative predictive values will generally remain below 70%.

[Cholesterol-lowering therapy; a recommendation from the Health Council]. / Cholesterolverlagende therapie; een advies van de Gezondheidsraad.

The recent report on lipid lowering therapy from the Netherlands Health Council is largely in agreement with the 1998 guidelines made at the Dutch Institute for Health Care Improvement CBO on the same topic. In addition to advice for a healthy life style and no smoking, lipid lowering therapy (particularly statins) is recommended in: patients with familial hyperlipidaemia; patients with atherosclerotic disease and a total cholesterol > 5.0 mmol/l; patients with diabetes and multiple risk factors including a total cholesterol > 5.0 mmol/l; other persons with markedly increased risk for development of coronary artery disease. The report does not dwell upon implementation and effects of the recommendations or on the question what preventive efforts are desirable for persons without manifest cardiovascular disease. In practice, prescribing the recommended medication is more successful than attempts to change the life style. The effects of multifactorial life style intervention may be considerable, however. The high social costs of cholesterol-lowering treatment should be regarded as an investment in health.

Assessment of coronary angiograms prior to and after treatment with abciximab, and the outcome of angioplasty in refractory unstable angina patients. Angiographic results from the CAPTURE trial.

BACKGROUND: The CAPTURE study (c 7E3 A nti P latelet T herapy in U nstable Re fractory angina) was designed to assess outcome in patients with refractory angina undergoing angioplasty, receiving either abciximab or placebo. METHODS: One thousand two hundred and sixty-five patients with refractory unstable angina, defined as recurrent myocardial ischaemia despite medical treatment including heparin and nitrates were enrolled. After angiography, patients received an infusion of abciximab or placebo over 18-24 h preceding angioplasty, continuing until 1 h after the procedure. In 1197 patients undergoing angioplasty the angiographic committee centrally reviewed the baseline as well as the procedural angiograms. Coronary flow and lesion characteristics were assessed in the baseline angiogram as well as before intervention. Angiographic outcome, reason for failure as well as complications were assessed after angioplasty. RESULTS: At 30 days follow-up, patients receiving abciximab (n=595) compared with placebo (n=602) had a 30% reduction in the composite primary end-point death, myocardial infarction or urgent (re)intervention: 10.8% vs 15.4% (P=0.017). Baseline demographics were identical in the angiogram available group compared with the total study group. At 30 days, the non-angiogram available patients showed a higher incidence of events compared to those in whom the angiogram was reviewed: 19.4 vs 13.1% (P=ns). Lesion characteristics and coronary flow were not different at baseline between the placebo and abciximab groups. A primary end-point was reached in 9.6% of both placebo and abciximab patients with type A or B(1)lesions, in 17.0% vs 12.0% with type B(2)lesions, and in 19.1% vs 11.5% with type >B(2)or C lesions. Sixty-one percent of placebo and abciximab patients had TIMI 3 flow at baseline angiography. Pre-angioplasty TIMI 3 flow was observed in 69% and 72% respectively. The thrombus was resolved between the angiograms in 22% and 43% respectively, in the placebo and abciximab groups (P=0. 033). Angiographic success of the procedure was achieved in 88% and 94% in the placebo and abciximab patients, respectively (P<0.001). Stents were implanted in the ischaemia-related artery in 56 and 60 patients, respectively. However, failure of the stent procedure was more frequent in the placebo group than in the abciximab group, nine vs no patients (P=0.003). CONCLUSION: More frequent thrombus resolution was observed and a higher angiographic success rate was achieved in patients treated with abciximab before and during angioplasty compared with placebo. Patients with complex lesions as the underlying pathology reached fewer end-points if treated with abciximab before and during angioplasty.

Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study.

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.

[Guidelines and costs]. / Richtlijnen en kosten.

There is a growing interest in developing clinical guidelines which support the efficiency of medical care by weighting the potential benefits against the costs of interventions. In the recently developed Dutch guideline on reduction of serum cholesterol concentration a formal cost-effectiveness analysis is included. Based on epidemiological arguments a cost-effectiveness ratio of 40,000 Dutch guilders per life year gained was found. In comparison with other preventive health care programmes this amount was considered acceptable. In the past physicians have often taken costs into account in an implicit way when making clinical decisions. The results of the cost-effectiveness analysis vary particularly with the costs of the used statins. In the past physicians have often taken costs into account in an implicit way when making clinical decisions. However, in view of the increase in health care expenditures, it has become the responsibility of physicians to take costs into account more explicitly. Clinical guidelines with a cost-effectiveness analysis can be useful in helping physicians to provide efficient medical care.

[National guidelines for clinical decisions, a methodological view]. / Landelijke richtlijnen voor het klinisch handelen, een methodologische beschouwing.

Medical guidelines used to be based mostly on expertise and experience. Since the eighties they are increasingly scientifically founded. In recent years results of possible treatments have been estimated quantitatively and compared. In drawing up the consensus text 'Antithrombotic prophylaxis of vascular events in patients with manifest atherosclerotic vasculopathy' the preparatory committee, after systematic arrangement of the relevant literature, made maximal use of the results of randomized prospective clinical trials of good quality and sufficient magnitude, published in peer-reviewed journals. For most indications, the pathophysiological reasoning and the study results were in agreement. A demonstrated effect of a treatment was evaluated on the basis of its magnitude and related to the associated costs and efforts. For the consensus 'Treatment and prevention of coronary heart disease by lowering the serum cholesterol level' use was made of estimates of effects of treatment with statins versus placebo. For prevention of total mortality and non-fatal myocardial infarctions and strokes, the relative risk reduction was 30-35%. The decrease of the absolute risk depended on the initial risk. The committee was of the opinion that treatment would be useful given an absolute risk of 25% of a (subsequent) manifestation of cardiovascular disease within 10 years. This would cost Dfl. 40,000.-per year of life gained, which the committee considered acceptable. In the argumentation of guidelines there is a trend to systematic evaluation and quantitative application of the research data. Subjective assessments remain necessary, particularly the evaluation of clinical relevance of observed or assumed effects of treatments.

[Therapy and prevention of coronary heart diseases through lowering of the serum cholesterol levels; third consensus 'Cholesterol'. Consensus Working Group, CBO]. / Behandeling en preventie van coronaire hartziekten door verlaging van de serumcholesterolconcentratie; derde consensus 'Cholesterol'.

For the second time the consensus text for lipid lowering therapy is revised. In angiographic studies it was shown that a decrease in the total cholesterol as well as the low-density lipoprotein cholesterol level results in a reduction of the progression of vascular disease. Furthermore, intervention trials demonstrated that therapy with cholesterol synthesis inhibitors reduces not only both the cardiovascular and total mortality, but also other manifestations of coronary heart disease (CHD). Hypercholesterolaemia is treated with a low-fat diet and normalisation of the weight. For individuals, this might result in a reduction of the risk for myocardial infarction or death and for the population in a decrease of the mean serum cholesterol concentration and the incidence of CHD. The indication for drug therapy is founded on the expected effectiveness to reduce the incidence of (new manifestations of) CHD, which is related to the level of the absolute risk of vascular disease. In persons without known vascular diseases this risk is calculated from the total and high-density lipoprotein cholesterol ratio, age, sex, blood pressure, diabetes mellitus, and smoking. Treatment with cholesterol synthesis inhibitors must be considered in (a) patients with familial hypercholesterolaemia, (b) all patients with a history of myocardial infarction or other symptomatic vascular disease with a total cholesterol concentration above 5.0 mmol/l and a life expectancy of at least five years; (c) persons with a combination of diabetes mellitus, hypertension, hypercholesterolaemia and high risk for development of CHD, rising from 25% per 10 years at the age of 40 years to 35-40% per 10 years at the age of 70 years, with a life expectancy of at least five years. If these guidelines are followed, the upper limit of the calculated cost-effectiveness is about Dfl. 40,000 per life year gained. The working group judges this reasonable in comparison with other therapeutic interventions in the Netherlands.

Reperfusion therapy for acute myocardial infarction. Which strategy for which patient?

Several modes of reperfusion therapy for evolving myocardial infarction (MI) have been developed, which differ in terms of effectiveness, complexity and costs. Reperfusion resources are often restricted by budgetary or logistical circumstances. To arrive at an equitable distribution of treatment options, physicians should therefore consider which treatment to apply in which patient. Two major questions which arise in this respect are discussed here: what is the treatment effect in an individual patients, and what is an equitable resource allocation? Currently, the most relevant treatment options are: streptokinase (1.5MU over 1h), reteplase (2 boluses of 10MU), alteplase (tissue plasminogen activator; t-PA) [100mg over 1.5 hours] and immediate angioplasty. In combination with aspirin, streptokinase leads to an almost 40% mortality reduction at 1 month compared with placebo [from 13.2 to 8.0%; Second International Study of Infarct Survival (ISIS-2) trial]. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-1) study demonstrated a further mortality reduction by early combination therapy of aspirin, intravenous heparin and alteplase vs aspirin, heparin (either intravenous or subcutaneous) plus streptokinase (from 7.3 to 6.3%). The clinical effects of reteplase fall somewhere between those of streptokinase and alteplase. Combined analysis of the angioplasty trials suggests that angioplasty is superior to thrombolysis, especially in patients with a high cerebral bleeding risk. The noticed gradient of efficacy runs parallel to a gradient of costs and complexity: streptokinase is the least costly treatment option while direct angioplasty is the most expensive and complex. Subgroup analyses indicate that there are neither apparent deviations in the relative effect of reperfusion therapy as compared to control treatment, nor in the additional effect of more intensive therapy (alteplase) upon 'standard' therapy (streptokinase). Consequently, the absolute number of deaths avoided by reperfusion therapy appears to be greatest in those groups with a high mortality risk without therapy. There is one major exception: in patients treated early after symptom onset a much greater relative mortality reduction is observed than in those treated later. Owing to the higher mortality risk, the life expectancy of a patient with MI is shorter than that of an 'average' person of the same community and the same age. Since mortality reduction of reperfusion therapy is maintained at long term follow-up, part of this potential loss can be regained. This 're-gain of lost years' is judged to be the ultimate treatment effect in an individual patient. An equitable treatment allocation should be such that patients who will benefit most will receive the most effective therapy, while patients with similar expected benefit will be offered the same mode of therapy. The conclusion is that treatment guidelines or protocols can be very useful in clinical practice, especially if rapid decision making is of vital importance.

Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic Complications.

Cost-effectiveness analyses are routinely performed to determine whether the additional cost of a novel therapy is balanced by additional effectiveness. The definitions of costs and effects involve a variety of assumptions, both in general economic terms and with regard to the specific medical setting under consideration. Similarly, differing criteria for acceptability of cost-effectiveness estimates can be used to generate different conclusions regarding cost-effectiveness. The issues and problems inherent in economic evaluation are discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) study in high-risk patients undergoing percutaneous transluminal coronary angioplasty.

Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic Complications.

Cost-effectiveness analyses are routinely performed to determine whether the additional cost of a novel therapy is balanced by additional effectiveness. The definitions of costs and effects involve a variety of assumptions, both in general economic terms and with regard to the specific medical setting under consideration. Similarly, differing criteria for acceptability of cost-effectiveness estimates can be used to generate different conclusions regarding cost-effectiveness. The issues and problems inherent in economic evaluation are discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) study in high-risk patients undergoing percutaneous transluminal coronary angioplasty.

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.

Estimated gain in life expectancy. A simple tool to select optimal reperfusion treatment in individual patients with evolving myocardial infarction.

Currently several modes of reperfusion therapy for acute myocardial infarction are available. Streptokinase, accelerated alteplase and direct angioplasty are the most frequently used. These options are increasingly effective, but are also increasingly complex and costly. Since, unfortunately, physicians are often restricted by budget limitations, choices must be made in clinical practice to provide optimal therapy to individual patients. In order to guide such decision making, we developed a model to predict the expected benefit of therapy in terms of gain in life expectancy. Patients' life expectancy will decrease after infarction. Part of this loss can be prevented by early reperfusion therapy. The clinical benefit of therapy ranges from negligible gain in patients with small infarcts treated relatively late to an expected gain of more than 2 years in patients with extensive infarction treated within 3 h of onset of symptoms. The expected benefits are presented in a set of tables and depend on age, previous infarction, estimated infarct size, treatment delay and intracranial bleeding risk. With the help of these table, resources will be allocated in such a manner that patients who will benefit the most will receive the most effective therapy. Patients with similar expected treatment benefit will be offered the same mode of therapy. Future life years were discounted at 5% per year. The arbitrary thresholds currently applied for decision making at the Thoraxcenter are: no reperfusion therapy when the estimated gain in discounted life expectancy was < 1 month, streptokinase for 1-4 months and accelerated alteplase for a gain > or = 5 months. Direct angioplasty is recommended in patients with an estimated gain > or = 12 months, and in patients with an increased risk of intracranial bleeding. In this way, approximately 80% of our patients will be treated with thrombolytics (40% streptokinase and 40% accelerated alteplase), while in 10% direct angioplasty will be initiated. Patients with small infarcts presenting late will not receive reperfusion therapy. These threshold values have been chosen arbitrarily, and different thresholds may be selected in other centres. However, the developed model would guarantee that treatment decisions are made in a consistent manner, to provide optimal therapy for patients with evolving myocardial infarction, in spite of limited resources.