Thrombolytic therapy in acute myocardial infarction.
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Humans↗
Biomedical subjects
M G Franzosi
Publications and source records attributed to M G Franzosi.
Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations: GISSI-Prevenzione mortality risk chart.
AIMS: To present and discuss a comprehensive and ready to use prediction model of risk of death after myocardial infarction based on the very recently concluded follow-up of the large GISSI-Prevenzione cohort and on the integrated evaluation of different categories of risk factors: those that are non-modifiable, and those related to lifestyles, co-morbidity, background, and other conventional clinical complications produced by the index myocardial infarction. METHODS: The 11-324 men and women recruited in the study within 3 months from their index myocardial infarction have been followed-up to 4 years. The following risk factors have been used in a Cox proportional hazards model: non-modifiable risk factors: age and sex; complications after myocardial infarction: indicators of left ventricular dysfunction (signs or symptoms of acute left ventricular failure during hospitalization, ejection fraction, NYHA class and extent of ventricular asynergy at echocardiography), indicators of electrical instability (number of premature ventricular beats per hour, sustained or repetitive arrhythmias during 24-h Holter monitoring), indicators of residual ischaemia (spontaneous angina pectoris after myocardial infarction, Canadian Angina Classification class, and exercise testing results); cardiovascular risk factors: smoking habits, history of diabetes mellitus and arterial hypertension, systolic and diastolic blood pressure, blood total and HDL cholesterol, triglycerides, fibrinogen, leukocytes count, intermittent claudication, and heart rate. Multiple regression modelling was assessed by receiver operating characteristic (ROC) analysis. Generalizability of the models was assessed through cross validation and bootstrapping techniques. POPULATION AND RESULTS: During the 4 years of follow-up, a total of 1071 patients died. Age and left ventricular dysfunction were the most relevant predictors of death. Because of pharmacological treatments, total blood cholesterol, triglycerides, and blood pressure values were not significantly associated with prognosis. Sex-specific prediction equations were formulated to predict risk of death according to age, simple indicators of left ventricular dysfunction, electrical instability, and residual ischaemia along with the following cardiovascular risk factors: smoking habits, history of diabetes mellitus and arterial hypertension, blood HDL cholesterol, fibrinogen, leukocyte count, intermittent claudication, and heart rate. The predictive models produced on the basis of information available in the routine conditions of clinical care after myocardial infarction provide ready to use and highly discriminant criteria to guide secondary prevention strategies. CONCLUSIONS AND IMPLICATIONS: Besides documenting what should be the preferred and practicable focus of clinical attention for today's patients, the experience of GISSI-Prevenzione suggests that periodically and prospectively collected databases on naturalistic' cohorts could be an important option for updating and verifying the impact of guidelines, which should incorporate the different components of the complex profile of cardiovascular risk. The GISSI Prevenzione risk function is a simple tool to predict risk of death and to improve clinical management of subjects with recent myocardial infarction. The use of predictive risk algorithms can favour the shift from medical logic, based on the treatment of single risk factors, to one centred on the patient as a whole as well as the tailoring of medical interventions according to patients' overall risk.
Adult↗
Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data.
BACKGROUND: Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infarction. Recent advances in pharmacological treatment of myocardial infarction may have changed the impact of this arrhythmia. OBJECTIVE: To assess the incidence and prognosis of atrial fibrillation complicating myocardial infarction in a large population of patients receiving optimal treatment, including angiotensin converting enzyme (ACE) inhibitors. METHODS: Data were derived from the GISSI-3 trial, which included 17 944 patients within the first 24 hours after acute myocardial infarction. Atrial fibrillation was recorded during the hospital stay, and follow up visits were planned at six weeks and six months. Survival of the patients at four years was assessed through census offices. RESULTS: The incidence of in-hospital atrial fibrillation or flutter was 7.8%. Atrial fibrillation was associated with indicators of a worse prognosis (age > 70 years, female sex, higher Killip class, previous myocardial infarction, treated hypertension, high systolic blood pressure at entry, insulin dependent diabetes, signs or symptoms of heart failure) and with some adverse clinical events (reinfarction, sustained ventricular tachycardia, ventricular fibrillation). After adjustment for other prognostic factors, atrial fibrillation remained an independent predictor of increased in-hospital mortality: 12.6% v 5%, adjusted relative risk (RR) 1.98, 95% confidence interval (CI) 1.67 to 2.34. Data on long term mortality (four years after acute myocardial infarction) confirmed the persistent negative influence of atrial fibrillation (RR 1.78, 95% CI 1.60 to 1.99). CONCLUSIONS: Atrial fibrillation is an indicator of worse prognosis after acute myocardial infarction, both in the short term and in the long term, even in an unselected population.
Aged↗
Cost-effectiveness analysis of n-3 polyunsaturated fatty acids (PUFA) after myocardial infarction: results from Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)-Prevenzione Trial.
OBJECTIVE: To estimate the cost effectiveness of treatment with n-3 polyunsaturated fatty acids (PUFA) for secondary prevention after myocardial infarction (MI). DESIGN AND SETTING: The cost-effectiveness analysis of n-3 PUFA treatment after MI was based on morbidity and mortality data and the use of resources obtained prospectively during the 3.5 year follow-up period of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)-Prevenzione study. The cost-effectiveness analysis took into account the incremental number of life-years gained and the incremental costs for hospital admissions, diagnostic tests and drugs, applying a 5% discount rate. The value for money of n-3 PUFA treatment was assessed using the cost-effectiveness ratio and the number needed to treat (NNT) approach. PERSPECTIVE: Third-party payer. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratio for n-3 PUFA in the basecase scenario was 24,603 euro (EUR, 1999 values) per life-year gained (95% confidence interval: 22,646 to 26,930). Sensitivity analysis included the analysis of extremes, producing estimates varying from EUR15,721 to EUR52,524 per life-year gained. 172 patients would need to be treated per year with n-3 PUFA, at an annual cost of EUR68,000, in order to save 1 patient. This is comparable with the NNT value, and associated annual cost for simvastatin, but less costly than that for pravastatin. CONCLUSIONS: The cost effectiveness of long term treatment with n-3 PUFA is comparable with other drugs recently introduced in the routine care of secondary prevention after MI. Since the clinical benefit provided by n-3 PUFA is additive, this therapy should be added to the established routine practice, with additive costs.
Cost-Benefit Analysis↗
[Reperfusion after acute myocardial infarct with fibrinolytic therapy o combination reduced fibrinolytic therapy and a glycoprotein IIb/IIIa inhibitor: the GUSTO V study].
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Drug Therapy, Combination↗
[Susceptibility gene to infarct: a review of the literature].
The investigation on the susceptibility genes of myocardial infarction has initiated substantially in the last 20 years. Most efforts have been mainly addressed to identify and evaluate genes involved in those systems already suspected to be implicated in the pathogenesis of coronary heart disease. Principal examples are lipid metabolism, coagulation and fibrinolytic systems, membrane receptors of platelets, levels of plasma homocysteine and vascular tone. Therefore up to now, the identification of the genetic factors of myocardial infarction has been carried out through case-control association studies employing a "candidate gene" approach. This method has often led to controversial results, usually difficult to compare. This is an attempt to provide a progress report on the principal susceptibility genes of coronary heart disease.
Case-Control Studies↗
[PROCARDIS: A current approach to the study of the genetics of myocardial infarct].
Coronary artery disease is a complex and multifactorial pathology. Although the environmental component of coronary artery disease has been thoroughly investigated and is hence well known, knowledge about the genetic factors implicated in this disease is still scarce. Technological advances and the fact that the Human Genome Project has almost been completed allow the application of approaches that were not feasible few years ago to the genetic investigation of complex diseases. The aim of the PROCARDIS study is to identify new susceptibility genes of precocious coronary artery disease, through a genome-wide screen applying statistical methods of linkage analysis followed by a family-based association study. The originality of PROCARDIS lies in the fact that it is an international multicenter study. This allows recruitment of a very large number of individuals so that the population size, considered up to now unachievable, is adequate for the aims of the study.
Genetic Linkage↗
Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.
OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. METHODS: This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). RESULTS: Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. CONCLUSIONS: Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.
Aged↗
[Hirudin is superior to heparin in reducing cardiovascular mortality, infarct and refractory angina in patients with unstable angina or myocardial infarct without elevation of the ST tract].
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Angina, Unstable↗
Prognostic significance of double product and inadequate double product response to maximal symptom-limited exercise stress testing after myocardial infarction in 6296 patients treated with thrombolytic agents. GISSI-2 Investigators. Grupo Italiano per lo Studio della Sopravvivenza nell-Infarto Miocardico.
BACKGROUND: The aim of this study was to evaluate the prognostic significance of the pressure-rate product (PRP) obtained during exercise stress testing and of its change from rest to maximal exercise (dPRP) in a population of survivors of acute myocardial infarction treated with thrombolytic agents. METHODS AND RESULTS: Survivors of acute myocardial infarction (n = 6251) from the GISSI-2 database, who underwent a maximal symptom-limited exercise test with either bicycle ergometer or treadmill, were followed up for 6 months. PRP and dPRP values were dichotomized (</=21,700 and >21,700, </=11, 600 and >11,600, respectively) and analyzed in a multivariate Cox model individually and simultaneously with other ergometric variables. Six-month mortality rate was 0.8% in the high PRP group and 2.0% in the low PRP group. Low PRP was an independent predictor of 6-month mortality rate (relative risk [RR] 1.97, 95% confidence interval [CI] 1.24 to 3.13). Patients with low dPRP had mortality rates higher than patients with high dPRP (2.1% vs 0.8%). At the multivariate analysis, low dPRP showed negative predictive value (RR 1.97, 95% CI 1.23 to 3.16). A further multivariate analysis was performed with PRP and dPRP, also adjusting for low work capacity, abnormal systolic blood pressure response to exercise, and symptomatic-induced ischemia. The results showed that low work capacity, low PRP, and symptomatic exercise-induced ischemia were still significantly associated with higher 6-month mortality rate (P =.04,.02, and.05; RR = 1.68, 1.71, and 1.78 respectively). CONCLUSIONS: PRP is a predictive index to assess prognosis in survivors of acute myocardial infarction treated with thrombolytic agents able to perform an exercise test after acute myocardial infarction, but its usefulness appears to be limited, considering that these patients were at low risk.
Aged↗
Internet for clinical trials: past, present, and future.
The Internet and World Wide Web have recently been introduced into the management of some aspects of large-scale clinical trials such as remote randomization and data entry and the distribution of information on trial progress. Electronic mail and websites have also been used to enhance communication among people involved in a clinical trial. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico acuto (GISSI) used telecommunications and the Internet in some recent large-scale clinical trials. GISSI constructed a website to keep the medical and cardiology community informed about the progress of its studies. Websites for clinical trials could play an important role in the future, especially in international clinical trials. The website could provide information such as study material and study news and tools such as electronic forums on protocol application for use by investigators around the world. This article describes the GISSI experience and outlines an appropriate structure for a clinical trial website.
Clinical Trials as Topic↗
Ten-year follow-up of the first megatrial testing thrombolytic therapy in patients with acute myocardial infarction: results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 study. The GISSI Investigators.
BACKGROUND: We conducted a 10-year follow-up of the 11 712 patients with acute myocardial infarction randomized in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 study, the first large trial assessing thrombolytic therapy. METHODS AND RESULTS: Information on survival at 10 years was obtained for the 93% of all randomized patients through the census offices of their towns of residence. The difference in survival produced by streptokinase and sustained up to 1 year was still significant at 10 years (log-rank test, P=0.02), with the absolute benefit of 19 (95% CI 1 to 37) lives saved per 1000 patients treated. The time dependence of the extent of the benefit was confirmed, as the higher mortality rate reductions found in patients treated earlier were still present at 10 years. In the overall population, most of the benefit was obtained before hospital discharge (RR 0.81, 95% CI 0.72 to 0.90), since no difference in survival between thrombolyzed and control patients discharged alive was found at 10 years (RR 0.98, 95% CI 0.90 to 1.06). However, a slight albeit nonsignificant divergence of the survival curves of patients randomized within the first hour was observed [90 (95% CI 34 to 146) lives saved per 1000 at 10 years versus 72 (95% CI 37 to 107) lives saved at hospital discharge]. CONCLUSIONS: The benefits of a single intravenous infusion of 1.5 million units of streptokinase in prolonging survival of patients with acute myocardial infarction is sustained up to 10 years, with a still-evident trend in favor of the patients admitted earlier.
Age Factors↗
Administration of thrombolytic therapy to 17,944 patients with acute myocardial infarction: the GISSI-3 database.
BACKGROUND: There is growing interest in assessing therapy for acute myocardial infarction. Because thrombolysis was not a study therapy in the GISSI-3 trial, the decision about thrombolysis was left to the responsible physicians. We evaluated the data on thrombolytic therapy among patients with acute myocardial infarction enrolled in the GISSI-3 trial to study the relation between rate of prescription and the characteristics of patients and participating coronary care units. METHODS: Complete clinical data were available for 17,944 patients randomized between June 1991 and July 1993 from 200 coronary care units in Italy. Demographic and clinical information were obtained for each patient, and each coronary care unit was classified according to patient volume, level of technology, and wide geographic area in which it was located. A multivariate logistic regression was performed with administration of thrombolytic therapy as the dependent variable and previously defined clinical and structural variables as independent variables. RESULTS: The most important factor in administration of thrombolytic therapy was that less than 6 hours elapse from symptom onset to hospital admission (odds ratio [OR] 14.05; 95% confidence interval [CI] 12.3 to 16.0). Next were location of coronary care unit in southern Italy (OR 1.81; 95% CI 1.62 to 2.01), presence of ST elevation at entrance electrocardiogram ECG (OR 1.47; 95% CI 1.35 to 1.61), absence of previous myocardial infarction (OR 1.35; 95% CI 1.22 to 1.49), and presence of catheterization laboratory or cardiac surgery program or both in the same hospital (OR 1.24; 95% CI 1.14 to 1.35). Coronary care units with high or low patient volume did not show different rates of administration of thrombolytic agents. CONCLUSIONS: The GISSI-3 experience confirmed a high rate of prescription of thrombolytic therapy to patients admitted within 6 hours of symptom onset and those with ST-segment elevation on entrance electrocardiogram. It demonstrated that patients admitted to coronary care units with catheterization laboratories or cardiac programs or both have higher chances of receiving thrombolytic treatment than those admitted to hospitals without these capabilities.
Adult↗
Cost-effectiveness analysis of early lisinopril use in patients with acute myocardial infarction. Results from GISSI-3 trial.
The cost effectiveness of early treatment with lisinopril in acute myocardial infarction (MI) was estimated using survival and cost data gathered prospectively during the hospitalisation of the overall population of patients enrolled in the third study of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI-3), which assessed the efficacy of early (within 24 hours) treatment with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for 6 weeks in a group of 19,394 relatively unselected patients with acute MI. A statistically significant reduction in 6-week mortality was achieved among patients treated with lisinopril when compared with patients allocated to the control group (absolute reduction in mortality: 7.5 +/- 3.6 lives saved per 1000 treated patients). The comparative cost-effectiveness ratio for the use of lisinopril, expressed as cost per additional survivor among patients randomised to receive lisinopril, was $US2080 per life saved (1993 values). The sensitivity analysis conducted to examine the effects of varying the estimated absolute reduction in mortality throughout its 95% confidence interval, which ranged from 14.6 to 0.4 lives saved per 1000 treated patients, showed that the cost-effectiveness ratios consequently vary from $US1121 to $US40,910 per life saved. The cost effectiveness of early treatment with lisinopril of a relatively unselected population of patients with acute MI compares very favourably with that of other therapies judged to be worthwhile by the medical community.
Angiotensin-Converting Enzyme Inhibitors↗
Smoking is not a protective factor for patients with acute myocardial infarction: the viewpoint of the GISSI-2 Study.
BACKGROUND: A protective role of smoking in terms of mortality after acute myocardial infarction treated with thrombolytic agents was recently suggested, and this was attributed to the increased chance that smokers will achieve early complete perfusion after thrombolysis. The purpose of the present analysis of the GISSI-2 database was to evaluate the effect of smoking on in-hospital mortality, reinfarction and stroke rates. METHODS AND RESULTS: This analysis concerns 2611 (26.9%) nonsmokers, 1932 (19.9%) ex-smokers and 5151 (53.0%) active smokers with a first confirmed MI, treated with thrombolytic agents. The relationship between smoking habits and outcome was evaluated by unadjusted and adjusted analysis. Reinfarction and stroke rates were significantly lower in smokers (1.5 and 0.8% respectively) than in ex-smokers (2.5 and 1.1%) or nonsmokers (2.5% and 1.2%). In-hospital mortality significantly increased from 4.7% in smokers, to 7.6% in ex-smokers and 13.8% in nonsmokers. These differences may be due to the different characteristics of the three groups; in particular, smokers were younger than nonsmokers. After adjusted analysis, smoking was not confirmed to be a protective factor for reinfarction, stroke and mortality: OR 1.35 (95% Cl 0.91-2.02), 0.79 (95% Cl 0.58-1.06) and 0.80 (95% Cl 0.60-1.07) respectively. CONCLUSIONS: Active smokers presented a lower incidence of reinfarction, stroke and in-hospital mortality rates, but after adjustment for other clinical-epidemiological variables, the apparent protective role of smoking was not confirmed.
Acute Disease↗
Use of beta-blocking agents in secondary prevention after myocardial infarction: a case for evidence-based medicine? GISSI experience, 1984-1993. The Gruppo Italiano di Studio sulla Sopravvivenza nell'Infarto Miocardico (GISSI) Investigators.
AIMS: Many clinical trials conducted in the 1970s and early 1980s have shown that the long-term use of beta-blockers after an acute myocardial infarction significantly reduces mortality and reinfarction rates. This study assessed the impact of these findings in clinical practice. METHODS: We retrospectively analysed the beta-blocker prescriptions for 36,817 patients with acute myocardial infarction included in three large randomized clinical trials (Gruppo Italiano di Studio sulla Sopravvivenza nell'Infarto Miocardico--GISSI, 1, 2, and 3), conducted by a highly representative sample (about 75%) of Italian coronary care units in 1984-85, 1988-89 and 1991-93. RESULTS: The prescription of beta-blockers at discharge increased gradually from 8.5% in 1984-85 to 25.0% in 1988-89 and to 31.4% in 1991-93. A similar trend was apparent for beta-blocker prescriptions 6 months after acute myocardial infarction. The strongest predictors of beta-blocker prescription are the presence of post-infarctual angina and a history of arterial hypertension. Besides the classical contraindications, advanced age, transitory cardiac failure or arrhythmias in the acute phase of acute myocardial infarction are important predictors of nonprescription. CONCLUSION: The use of beta-blockers after acute myocardial infarction in Italy has increased more than three-fold in the last decade, but they are still prescribed to too few patients, especially those at higher risk, for whom the expected benefit is greater.
Adrenergic beta-Antagonists↗
Is anticoagulation therapy underused in elderly patients with atrial fibrillation?
Atrial fibrillation (AF) is found in 0.4% of the adult population and is a common condition in the elderly. Its prevalence increases with age to affect 5 to 14% of those over 74 years. Recent evidence indicates that, compared with sinus rhythm, AF is associated with a 4-to 7-fold increase in the risk of stroke. However, there is strong evidence from randomised trials that full anticoagulation with warfarin substantially reduces the risk of stroke. Elderly patients are among those at higher risk and stand to gain the most from such treatment. They are also at higher risk for complications related to anticoagulant therapy and this sometimes makes clinical decisions difficult. There is a strong rationale for prescribing warfarin for all patients with AF who are over 65 years and free of contraindications. Some concerns exist about the benefit: risk ratio of warfarin in patients aged > 75 years. The answer is probably to use low intensity anticoagulant therapy (international normalised ratio 2.0 to 3.0), which is safer but no less effective than higher intensity regimens. Few data are available in the literature on physicians' attitudes to anticoagulation in elderly patients with AF. Although the results of randomised clinical trials in AF seem to suggest that anticoagulants and/or aspirin (acetylsalicylic acid) are underused in the elderly, over 90% of the patients initially screened were excluded from randomisation, making the sample highly selected. Compared with randomised controlled trials, some observational studies seem to indicate a higher likelihood of using anticoagulation and have targeted the intensity of anticoagulation according to age and clinical scenario.
Adult↗