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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.

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.

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.

Aspirin (ASA) and angiotensin-converting enzyme inhibitor (ACEi) therapy reduce mortality when administered early after the onset of myocardial infarction. ASA can antagonize some effects of ACEi therapy by inhibiting the synthesis of vasodilating prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive lisinopril or not to receive lisinopril within 24 hours of the onset of symptoms of myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi lisinopril in the postacute phase of acute myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum creatinine levels at 42 days were significantly higher in lisinopril group than in the control group. Systolic and diastolic blood pressures in lisinopril group were significantly lower than controls at 42 days. The effect of lisinopril on creatinine and blood pressure did not differ between the ASA and no-ASA groups. ASA does not decrease the mortality benefit of early lisinopril after myocardial infarction, nor does it increase the risk of major adverse events. Lisinopril is safe and effective when given early after the onset of myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.

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, 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.

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.

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.

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.

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.

Background: Mortality of diabetic patients with acute myocardial infarction (MI) remains high despite recent improvement in their management. There is a need to evaluate efficacy and safety of novel treatments of MI in this high-risk population. We evaluated whether treatment with an ACE inhibitor begun within 24 hours from the onset of symptoms is able to decrease mortality and morbidity of diabetic patients with acute MI., Methods and Results: A retrospective analysis of the data of the GISSI-3 study in patients with and without a history of diabetes was performed. Patients with suspected acute MI were randomized to treatment with lisinopril (2.5 to 5 up to 10 mg/d) with or without nitroglycerin (5 to 20 microg I.V. then 10 mg/d) begun within 24 hours and continued for 6 weeks. The main end point was mortality at 6 weeks, and the secondary end point was a combined evaluation of mortality and severe left ventricular dysfunction. Information on diabetic status was available for 18,131 patients (approximately 94% of the total population enrolled), of whom 2790 patients had a history of diabetes. Treatment with lisinopril was associated with a decreased 6-week mortality in diabetic patients (8.7% versus 12.4%; OR, 0.68; 95% CI, 0.53 to 0.86; 37+/-12 lives saved per 1000 treated patients), an effect that was significantly (P<.025) higher than that observed in nondiabetic patients. The survival benefit in diabetics was mostly maintained at 6 months despite withdrawal from treatment at 6 weeks (12.9% versus 16.1%; OR, 0.77; 95% CI, 0.62 to 0.95)., Conclusions: Early treatment with the ACE inhibitor lisinopril in diabetic patients with acute MI is associated with a decreased 6-week mortality. This beneficial effect supports a widespread and early use of ACE inhibitors in diabetic patients with acute MI. The burden of mortality plus morbidity for ventricular dysfunction in diabetics remains clinically important and warrants further testing of novel therapeutic approaches.

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.

Internet is the most important computer network in the world that allow access to large amounts of information and services. During the last months, the internet has grown very rapidly. At January 1996, 147 countries and 6,642,000 computers worldwide (73,000 in Italy) were connected, and 90 millions of users (700,000 in Italy) could access the network (also called the Net). The increase of interest has also grown in the medical field and many medical and biomedical resources are now accessible through the Internet: databases of images and videos of medical interest, research and medical centres, congresses, medical journals (such as British Medical Journal, Circulation, Journal of the American Medical Association, New England Journal of Medicine), medical associations (such as American Heart Association, American College of Cardiology and recently Associazione Nazionale del Medici Cardiologi Ospedalieri). Internet introduced new ways of communication between users: they could use the electronic mall, organize forums on some medical topics through the newsgroups and the mailing lists, access directly to the references of an electronic paper and contact the author by electronic mail. The aim of the current paper is to present the technical aspects a user should know before connecting to the Internet, the accessible cardiological resources and what they could offer to the users.

Background: The proportions of nonfatal acute myocardial infarctions (AMI) in Italy attributable to cigarette smoking, body mass, serum cholesterol level, hypertension, diabetes, and family history of AMI (attributable risks, AR) were estimated using data from a case-control study on 614 incident cases of AMI before age 75 with no history of ischemic heart disease and 792 control subjects admitted to the same hospitals where cases were identified for acute, nonneoplastic, cardio- or cerebrovascular conditions not known or suspected to be related to cigarette smoking., Methods: The study was conducted between September 1988 and June 1989 within the framework of the GISSI-2 clinical trial. We assumed a multiplicative model and thus the risk attributable to several factors combined is not the sum of those attributable to the single factors., Results: Overall the AR of smoking was 49%, and for cholesterol, body mass, family history of AMI, hypertension, and diabetes the AR were 49, 16, 14, 13, and 6%, respectively. Together these factors explained 85% of AMI cases. Though differences emerged for each single factor, the proportion of AMI explained by the six factors together was approximately the same for both sexes, while these factors accounted for 97% of AMI cases before age 50 (and smoking alone for 70%) and for 80% after age 50., Conclusions: This study confirms that interventions on well-defined risk factors could, in principle, lead to the avoidance of the great majority of myocardial infarctions in this population (i.e., about 80% before age 75 and about 95% before age 50).

Exercise testing helped in diagnosing postinfarction patients in the prethrombolytic era. Over the past decade acute myocardial infarction treatment has changed because of new thrombolytic therapies and consequently, the value of exercise testing is under debate. The GISSI-2 database allowed us to reevaluate the prognostic role of exercise testing in thrombolysed patients. The exercise test was performed in 6296 patients, on average 28 days after randomisation. The test was not performed in 3923 patients because of contraindications. The test was judged positive for residual ischaemia in 26% of the patients, negative in 38%, and non-diagnostic in 36%. Among the patients with a positive stress test result, 33% had symptoms, whereas 67% had silent myocardial ischaemia. The mortality rate was 7.1% among patients who did not have an exercise test and 1.7% [correction of 7.1%] for those with a positive test, 0.9% for those who had a negative test, and 1.3% for those who did not have a diagnostic test. In the adjusted analysis, symptomatic induced ischaemia, submaximal positive result, low work capacity, and abnormal systolic blood pressure were independent predictors of 6-month mortality (relative risks [RR] 2.54, 95% CI 1.27-5.08, 2.28, 1.17-4.45, 2.05, 1.23-3.42, and 1.86, 1.05-3.31, respectively). However, when these factors were tested simultaneously, only symptomatic induced ischaemia and low work capacity were confirmed as independent predictors of mortality (RR Cox 2.07, 95% CI 1.02-4.23 and 1.78, 1.06-2.99, respectively). Patients with a normal exercise response have an excellent medium-term prognosis and do not need further investigation. However, more evaluation should be devoted to the patients who cannot undergo exercise testing, because the potential to influence outcome appears to be much greater.

We studied a series of hemostasis factors in a group of patients selected from a cohort of 916 patients affected by MI from the GISSI-2 study population. Following a case-control design, 73 patients with a family history of thrombosis (the presence of at least two first degree relatives affected by MI and/or stroke before 65 years) were matched with MI patients with no family history of thrombosis. Blood collection could be performed 6 +/- 1 months after the acute phase following MI in 53 pairs of such patients. The presence of mixed disulphides (MDS) was significantly higher in patients with family history than in controls; MDS were detected in 7 cases and only in 1 control. No difference was found in contrast in the distribution of fibrinogen, factor VII, factor VIII, vWF, protein C, protein S, AT III, HC II, PAI-1, lipoprotein (a). Nevertheless, independently from the family history, in the whole population of MI patients studied, 21 cases of suspected deficiency of protein C were found. Sixteen out of 53 patients with family history of MI and/or stroke had a family history of MI only. In patients with family history of MI the t-PA antigen levels were significantly lower than in the control group (7.5 +/- 4.4 vs 11.1 +/- 3.5 ng/ml, t = -2.6, p < 0.02). In the whole population of MI patients and in patients with a family history of thrombosis t-PA antigen was positively correlated with PAI-1 antigen and vWF. The correlation with PAI-1 was lost in patients with family history of MI.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Recent clinical trials have shown increased, rather than decreased, mortality in patients treated with antiarrhythmic drugs after acute myocardial infarction., Objective: To determine whether these findings had an impact on prescription of antiarrhythmic drugs after acute myocardial infarction., Methods: We retrospectively analyzed the class I and III antiarrhythmic prescription data of 38,072 patients with acute myocardial infarction enrolled in three large randomized clinical trials endorsed by a highly representative sample (about 75%) of Italian coronary care units during the last 10 years. The first study was conducted in 1984 to 1985; the second, in 1988 to 1989; the pilot for the third, in 1991; and the third, in 1991 to 1994., Results: Total class I and III antiarrhythmic prescriptions after acute myocardial infarction was halved during the last decade, from 11.9% at discharge and 14.4% at follow-up in 1984 to 1985 to 5.8% and 5.8%, respectively, in 1991 to 1994. The trend was independent of the different distributions in the three studies of the patients' characteristics associated with antiarrhythmic use (ie, age > or = 70 years, anterior acute myocardial infarction, ventricular fibrillation during hospitalization, and Killip class > or = 2 at randomization). The same decreasing trend was observed for each antiarrhythmic drug. The drug most widely used was amiodarone, accounting for about half of the antiarrhythmic prescriptions, followed by mexiletine hydrochloride and propafenone hydrochloride; flecainide acetate was dropped from the prescription list after the publication of the Cardiac Arrhythmia Suppression Trial results., Conclusion: The negative results of the recent clinical trials on class I antiarrhythmic drug use after acute myocardial infarction have been rapidly transferred into routine clinical practice in Italy, since the proportion of patients who received class I and III antiarrhythmic drugs after acute myocardial infarction was halved from the early 1980s to the early 1990s.

Background: In the pre-thrombolytic era, several studies showed the effectiveness of beta-blocker administration in the treatment of patients (pts) with acute Myocardial Infarction (MI). Results from the ISIS-1 and GISSI trials suggested that the combined administration of beta-blocker and of thrombolytic drugs in the acute phase of infarction could lead to a better prognosis. The possibility of synergic effects from the associated administration of these drugs was confirmed by small clinical trials. In GISSI-2 study a large number of patients treated with thrombolytic drugs were given i.v. atenolol (10 mg) as recommended therapy, not following a randomized study design., Aim: We reviewed the data of the GISSI-2 study population in order to evaluate: 1) the number of pts treated with i.v. atenolol; 2) the anamnestic and clinical characteristics of treated und untreated pts; 3) the causes of exclusion from the beta-blocker therapy; 4) the causes of scheduled dose withdrawal and the incidence of side effects related to atenolol administration; 5) the interaction between atenolol and streptokinase (SK) and rtPA; 6) the incidence of relevant clinical events and the causes of death during the in-hospital period., Results: Among 12377 evaluated pts, 5616 (45.4%) were given atenolol i.v., 2772 received SK (49.5%) and 2844 (50.5%) rtPA. Mean age was 59.5 +/- 11.3 yrs in atenolol treated pts vs 63.4 +/- 10.9 yrs in untreated pts (p < 0.001); 34.1% of pts aged > 70 yrs vs 48.6% of younger pts (p < 0.00001) and 42.1% of females vs 46.2% of males (p < 0.003) received atenolol. Pts with previous MI received less frequently atenolol than those without MI (17.5% vs 13.5%, p < 0.00001). 88.5% of the treated pts was in Killip class I at entry (untreated 69.5%, p < 0.00001); anterior and lateral site, non-Q type and > or = 5 electrocardiographic leads with ST segment elevation were more frequently found in atenolol treated pts, inferior and unknown site in untreated pts. Among 6761 untreated pts, 32% did not receive atenolol for the occurrence of bradycardia, 15.2% for hypotension, 14.1% for heart failure, 7.2% for bronchospasm or history of asthma, 6.2% for bradycardia and hypotension, 0.3% for death; in 25% of the untreated pts, none of the above-mentioned causes was detectable. 1064 pts (18.9%) did not complete the scheduled dose of atenolol for the occurrence of bradycardia or atrioventricular block > or = II degree (7.3%), hypotension (7%), bradycardia and hypotension (1.8%), heart failure (0.7%), death (0.03%), other causes (1.9%). Transient hypotension was found more frequently in pts treated with SK than in those receiving rtPA (9.3% vs 4.8%, p < 0.0001), but the rate of persistent hypotension was not different in both groups (4.6%). During the hospital phase a higher incidence of advanced atrioventricular block (12.3% vs 4.3%), need of temporary or permanent pacing (5.6% vs 1.9%), sustained ventricular tachycardia (4.5% vs 2.8%), heart failure (12% vs 7.1%), ventricular fibrillation (8% vs 4.9%) and death (11.9% vs 5.1%) were shown in pts that were not given i.v. atenolol. Heart failure was the main cause of death in both groups (untreated 2.3% vs 2.2%); ventricular fibrillation (0.2% vs 0.48%), cardiac rupture (0.5% vs 1.4%), and electromechanical dissociation (0.9% vs 1.9%) were less frequent in treated pts., Conclusions: The absence of randomized design of atenolol administration limits the value of the differences found in the clinical outcome of the two groups of pts. In spite of that, the low incidence of death and side effects in treated pts, and the high percentage of pts who completed the scheduled dose of atenolol, confirm that the iv. administration of beta-blockers in the acute phase of the myocardial infarction is safe, well tolerated and suitable in almost an half of the patients submitted to thrombolytic therapy with SK or rtPA.(ABSTRACT TRUNCATED AT 400 WORDS)

Objectives: This analysis aimed to evaluate in a large patient cohort the relation between ST segment alterations after fibrinolytic therapy for acute myocardial infarction and 1) the combined end point of in-hospital mortality plus clinical congestive heart failure or extensive left ventricular damage, and 2) mortality 30 and 180 days after randomization., Background: Angina relief, enzyme release acceleration and ST segment normalization are related to coronary artery reperfusion and prognosis. Electrocardiographic (ECG) evaluation before and after fibrinolytic drug administration has been used to predict short- and long-term clinical outcome in acute myocardial infarction., Methods: Patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial underwent a standard ECG on admission and after 4 h of alteplase or streptokinase therapy; 7,426 recordings were suitable for ST segment analysis. A decrease > or = 50% in the sum of ST segment elevation in all ECG leads was adopted as the cutoff for predicting coronary artery patency. Recanalization was deemed to have occurred in 4,951 patients (group A) versus 2,475 patients without reperfusion (group B)., Results: Group A patients experienced a lower incidence of the combined end point than did group B patients (16.2% vs. 22.9%, respectively), as well as of all its components (death, clinical heart failure, ejection fraction < 35%, injured myocardial segment > 45%, QRS score > 10). Thirty- and 180-day mortality rates were lower in group A than group B (3.5% and 5.7% vs. 7.4% and 9.9%, respectively); relative risk (Cox) was 0.46 (95% confidence interval [CI] 0.37 to 0.57) for 30-day and 0.58 (95% CI 0.48 to 0.70) for 180-day mortality. Patients in group A had significantly less ventricular fibrillation and sustained ventricular tachycardia but more ischemic episodes (early recurrent angina plus myocardial infarction recurrence)., Conclusions: A simple, inexpensive instrumental evaluation, unaffected by different epidemiologic and clinical characteristics of the population analyzed, can allow early assessment of the effectiveness of fibrinolytic treatment with respect to the main clinical outcomes.

Objectives: This study was designed to reassess the prediction of recurrent nonfatal myocardial infarction in patients recovering from acute myocardial infarction after thrombolysis., Background: Recurrent nonfatal myocardial infarction is a strong and independent predictor of subsequent mortality. Current knowledge of risk factors for nonfatal reinfarction is still largely based on data gathered before the advent of thrombolysis. Thus, this prospective study was planned to identify harbinger of nonfatal reinfarction in the postinfarction patients of the multicenter Grouppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial., Methods: Predictors of nonfatal reinfarction at 6 months were analyzed by multivariate technique (Cox model) in 8,907 GISSI-2 survivors of myocardial infarction with clinical follow-up, relying on a set of prespecified variables reflecting residual ischemia, left ventricular failure or dysfunction, complex ventricular arrhythmias, comorbidity as well as demographic and historical factors., Results: The postdischarge to 6-month incidence rate of nonfatal reinfarction was 2.5%. Independent predictors of nonfatal reinfarction were cardiac ineligibility for exercise test (relative risk 2.97, 95% confidence interval [CI] 1.98 to 4.45), previous myocardial infarction (relative risk 1.70, 95% CI 1.22 to 2.36) and angina at follow-up (relative risk 1.50, 95% CI 1.10 to 2.04). On further multivariate analysis, performed in 6,580 patients with both echocardiographic and electrocardiographic monitoring data available, a history of angina emerged as an additional risk predictor (relative risk 1.58, 95% CI 1.10 to 2.25)., Conclusions: The 6-month incidence of nonfatal reinfarction is rather low in survivors of myocardial infarction after thrombolysis. Cardiac ineligibility for exercise testing and a history of coronary artery disease are risk predictors. Recurrent nonfatal infarction is not predictable by qualitative variables reflecting residual ischemia, except by postdischarge angina. Prediction of nonfatal reinfarction appears less accurate than prediction of mortality, as almost 50% of reinfarctions occur in patients without any of the identified risk factors.

Objectives: To test whether acute reperfusion of the infarct-related vessel after an acute myocardial infarction is associated with a subsequent reduction in spontaneous ventricular arrhythmias that is independent of ventricular ejection fraction, 1,944 patients from the GISSI-2 study population were studied. The patients were selected on the basis of a first myocardial infarction and the availability of two-dimensional echocardiographic ejection fraction and data on the number of premature ventricular contractions per hour on Holter monitoring., Background: It has been suggested that postthrombolytic reperfusion of the culprit vessel may be associated with an increased electrical stability of the infarcted heart, irrespective of its residual pump performance., Methods: The predischarge relation between ejection fraction and number of premature ventricular contractions per hour was plotted according to the occurrence (1,309 patients) or not (635 patients) of acute reperfusion, identified noninvasively according to the modifications of the ST segment in serial electrocardiograms obtained in the first 24 h after infarction., Results: The frequency of premature ventricular contractions increased in a linear fashion with decreasing ejection fraction in both cohorts (p < 0.005 and p < 0.0001); however, there was no significant difference between the slopes and the intercepts of the two regression lines, so that the relation between ejection fraction and number of premature ventricular contractions per hour could be adequately described by a single equation: y (number of premature ventricular contractions) = 33.0-0.42x (ejection fraction) (r = -0.107, p < 0.0001). The results were the same even when differences between group characteristics were accounted for in a multiple regression model., Conclusions: It is concluded that 1) the number of premature ventricular contractions per hour after an acute myocardial infarction is dependent in a linear, inverse fashion on the residual ventricular ejection fraction, and 2) this relation is independent of the occurrence of reperfusion in the acute phase of infarction.

Thrombolytic therapy improves outcome in patients with myocardial infarction but is associated with an increased risk of intracranial haemorrhage. For some patients, this risk may outweigh the potential benefits of thrombolytic treatment. Using data from other studies, we developed a model for the assessment of an individual's risk of intracranial haemorrhage during thrombolysis. Data were available from 150 patients with documented intracranial haemorrhage and 294 matched controls. 49 patients with intracranial haemorrhage and 122 controls had been treated with streptokinase, whereas 88 cases and 148 controls had received alteplase. By multivariate analysis, four factors were identified as independent predictors of intracranial haemorrhage; age over 65 years (odds ratio 2.2 [95% Cl 1.4-3.5]), body weight below 70 kg (2.1 [1.3-3.2]), hypertension on hospital admission (2.0 [1.2-3.2]), and administration of alteplase (1.6 [1.0-2.5]). If the overall incidence of intracranial haemorrhage is assumed to be 0.75%, patients without risk factors who receive streptokinase have a 0.26% probability of intracranial haemorrhage. The risk is 0.96%, 1.32%, and 2.17% in patients with one, two, or three risk factors, respectively. We present a model for individual risk assessment that can be used easily in clinical practice.

Objectives: This study was conducted to determine the role of insulin-dependent and noninsulin-dependent diabetes in the prognosis of patients after myocardial infarction and treatment with fibrinolytic agents., Background: Several studies have shown that diabetic patients have a high mortality rate after acute myocardial infarction. However, the impact of diabetes on survival in patients treated with fibrinolytic agents is still undefined. It is also not known whether the type of diabetes or gender affects prognosis., Methods: We analyzed prevalence and prognostic significance of a history of diabetes in patients enrolled in the GISSI-2 study, all of whom received fibrinolytic agents. The incidence of deaths in the hospital and at 6 months after study entry was computed for patients without diabetes and for insulin-dependent and noninsulin-dependent diabetic patients; relative risks were evaluated by univariate and multivariate analysis., Results: Information on diabetic status was available for 11,667 patients, 94.2% of those randomized in the GISSI-2 study. The prevalence of diabetes was higher in women than in men (8.75% vs. 1.85%, p < 0.01 for insulin-dependent and 23.7% vs. 13.8%, p < 0.01 for noninsulin-dependent diabetic patients). The type of fibrinolytic agent did not affect mortality rates; the increase in in-hospital mortality of diabetic patients was moderate and similar for men with insulin- and noninsulin-dependent diabetes (8.7% and 10.1%, respectively, vs. 5.8% in nondiabetic patients); in women, mortality was markedly higher for insulin-dependent and only slightly higher for noninsulin-dependent diabetic patients (24.0% and 15.8%, respectively, vs. 13.9% for nondiabetic patients). The adjusted relative risks were 1.9 (95% confidence interval 1.2 to 2.9) for insulin-dependent diabetic women and 1.4 (95% confidence interval 1.1 to 1.8) for noninsulin-dependent diabetic men. The mortality rate after discharge showed a similar gender difference, and in insulin-dependent diabetic women, prognosis was ominous even in the absence of left ventricular damage before discharge., Conclusions: A history of diabetes is associated with a worse prognosis after myocardial infarction, even in patients treated with fibrinolytic agents. Gender and type of diabetes appear to be critical in affecting survival. In men, both insulin-dependent and noninsulin-dependent diabetes are associated with a moderately higher mortality rate; in women, insulin-dependent diabetes is, in itself, a strong risk factor for death after myocardial infarction.

Background: The overall rate of mortality due to ischemic heart disease is known to increase progressively with age. We evaluated the relation between the mortality rate and age in patients with first myocardial infarctions treated with thrombolytic therapy., Methods: We studied 9720 patients with first infarctions who had been enrolled in the GISSI-2 trial. (This trial compared the efficacy of tissue plasminogen activator with that of streptokinase in patients with myocardial infarction.) Of these, only 35 percent had a history of angina. The relation between age and mortality during hospitalization and during the six months after discharge was determined by unadjusted and adjusted analyses., Results: The in-hospital mortality rate was 1.9 percent among patients 40 years old or younger, but it increased to 31.9 percent among those more than 80 years old; however, values for indicators of infarct size did not increase with age. Autopsies were performed in 20 percent of the 772 patients who died in the hospital; the findings showed that the frequency of cardiac rupture increased from 19 percent among patients 60 years old or younger to 86 percent among those more than 70 years old. The mortality rate for the first six months after hospital discharge also increased significantly with age. After adjustment for confounding variables, older age continued to be significantly associated with a higher risk of in-hospital and post-discharge death. When age was introduced into a multivariate model as a continuous variable, the risk of death was estimated to increase by about 6 percent per year for both in-hospital and six-month mortality rates., Conclusions: In patients with first myocardial infarctions who received thrombolytic therapy, age was a powerful independent predictor of both in-hospital and post-discharge mortality rates. The exponential, age-related increase in the mortality rate did not appear to be explained by larger infarcts.

The relationship between coffee consumption and acute myocardial infarction (AMI) was analyzed using data from a case-control study conducted in 1988 to 1989 within the framework of the GISSI-2 trial on streptokinase versus alteplase and heparin versus no heparin in the treatment of AMI. A total of 801 male patients with AMI and 792 control subjects who were hospitalized in several Italian regions for diseases unrelated to known or potential risk factors for cardiovascular diseases were included. Compared with coffee nondrinkers, the multivariate relative risks (RRs), after allowance for age, education, body mass index, smoking habits, alcohol consumption, family history of AMI, cholesterol level, history of diabetes, and hypertension, were 0.8 (95% confidence interval (CI), 0.5 to 1.2) for consumption of one cup/d, 1.3 (95% CI, 0.9 to 2.0) for two cups/d, 1.8 (95% CI, 1.1 to 2.7) for three cups, 2.5 (95% CI, 1.5 to 4.1) for four cups, and 2.6 (95% CI, 1.6 to 4.2) for five cups or more. The trend in risk with dose was statistically significant (P < 0.001). Duration of coffee consumption was not associated with the risk of AMI. The RRs for daily coffee consumption were elevated across strata of various covariates, including age, smoking habits, cholesterol level, diabetes, and hypertension, with a particularly elevated (although not significantly heterogeneous) estimate in patients younger than 50 years (RR, 5.7; 95% CI, 3.0 to 10.9 for four or more cups/d). The RR in patients who drank four or more cups of coffee per day and were current smokers was 8.1 (95% CI, 5.1 to 13.0), suggesting an unfavorable effect on the combination of cigarette smoking and high coffee intake on the risk of AMI.

Background: Many trials in patients with acute myocardial infarction have demonstrated that thrombolytic therapy is not associated with an excessive risk of stroke, as compared with conventional treatment. However, the incidence of various forms of stroke in patients treated with different thrombolytic and antithrombotic regimens and the associated effect of risk factors for stroke are largely unknown., Methods: Strokes occurring in patients hospitalized with acute myocardial infarction who were enrolled in either of two large trials were analyzed. The patients were randomly assigned to receive streptokinase (1.5 million units) or recombinant tissue plasminogen activator (t-PA) (100 mg) and also randomly assigned to receive subcutaneous heparin or no heparin. Ninety-one percent of the patients also received aspirin., Results: Complete data were available on 20,768 patients. A total of 236 (1.14 percent) had strokes in the hospital; 0.36 percent had hemorrhagic strokes, 0.48 percent ischemic strokes, and 0.30 percent strokes of undefined cause. Patients treated with t-PA had a small but significant excess of stroke as compared with those who received streptokinase (1.33 vs. 0.94 percent; adjusted odds ratio, 1.42; 95 percent confidence interval, 1.09 to 1.84). The administration of subcutaneous heparin in addition to a thrombolytic agent did not increase the risk of stroke (risk with heparin, 1.13 percent; without heparin, 1.14 percent). Older age, a higher Killip class, and the occurrence of anterior infarction significantly increased the risk of stroke, whereas a higher body-mass index or a history of hypertension, diabetes, or smoking did not., Conclusions: Patients with acute myocardial infarction who receive thrombolytic therapy have a small risk of stroke. Treatment with t-PA as compared with streptokinase resulted in a small but significant excess of stroke. Subcutaneous heparin, given together with t-PA or streptokinase and aspirin, did not result in an increased risk of stroke.

The 1980s has been a critical decade for the management of acute myocardial infarction (MI) because of the concentration in a very short time span of innovative results produced by a new generation of trials, in which thrombolysis has been the preeminent topic. The message coming from the results in the more than 50,000 patients included in the five key trials is simple and clear: thrombolysis, of any type, is the cornerstone of acute treatment of MI, and it works well to produce a very favorable epidemiologic picture. In the GISSI-2 trial, the nationwide adoption of a package of recommended treatments centered on thrombolysis for the overall population of patients with an acute MI has produced a relevant modification of the natural history of the disease, reducing the in-hospital mortality by about 40% in few years (from 13% to 8.8%). In particular, in the great majority of cases (patients aged less than 70 years in Killip class I with a first acute MI), the mortality has gone down to 3%, making a further reduction very hard to obtain with new drugs or strategies. In this context, we will discuss the concept of the relevance for clinical practice of obtaining even greater patency rates with new thrombolytic agents (hopefully more efficient and safe) or with new combinations of traditional agents.

Trials on chemotherapy of advanced ovarian cancer published between 1975-88 were systematically reviewed for quality (according to the method of Chalmers) and consistency of tested hypotheses with a view to a meta-analysis of all published studies in the field. Median overall, internal and external validity scores were 47%, 43% and 53%, respectively. No association was found between scores and key features of trials, such as percentage studies with significant results in response or survival or percentage studies with high or low follow-up retention (withdrawal rates less than or greater than or equal to 15%). Only 21% of trials reported a fully blind randomization procedure and only in 13% were drop-outs accounted for by the intent-to-treat method. Only 4 trials entered more than 150 patients per arm, a sample size consistent with detection of an absolute difference of 11% in mortality. The majority of trials (58%) investigated the role of combination regimens versus a single-agent control arm. The remaining trials tested different polychemotherapies. However, within these two general issues, treatment options were quite heterogeneous: seven subgroups were identified by whether cisplatin was present in either the treatment or the control arm. We conclude that the internal coherence and development of randomized clinical trials in advanced ovarian cancer and their methodologic soundness are quite poor. In this situation meta-analysis cannot go beyond a systematic attempt to answer a very general "treatment effectiveness" question.

Population trials on myocardial infarction have produced significant advances in therapeutic results. The first clearly stated aim of the GISSI-2 protocol was the assessment of the overall benefit to a population attributable to the application of a package of pharmacological treatments (thrombolysis, intravenous beta blockade, and oral aspirin) shown effective in reducing mortality in large-scale randomized clinical trials. At variance with the classical concept of trials, a clinical epidemiological interest came first: The comparison between drugs was considered a main target of the investigation only within that broader framework, and was explicitly formulated as the direct confrontation between two concepts or two generations of thrombolysis. A selective, highly efficient, and specific new thrombolytic agent, tissue plasminogen activator (tPA), is compared with streptokinase with the expectation that the more selective approach could enhance the benefits of specificity, drastically limiting the systemic risks aspects (hemorrhagic complications). The main results of GISSI-2 are summarized. GISSI-2 may be considered a reliable window on the epidemiology of AMI in a whole country. There are implications for the transfer of these clinical findings into public health applications and for the choice of future research priorities.

Despite the availability of safe and effective drugs for the treatment of acute myocardial infarction, nowadays, only a minority of patients arrive at the hospital early enough to receive the benefit of these treatments. The reason for this is still uncertain. Our intention was to review the literature on this topic, check if there were some issues that could be identified as delay-promoters, and see if any Italian data were available, in order to make a comparison with international data. We found a substantial agreement among the Authors that median total delay (i.e. the time between the onset of symptoms and the arrival at the hospital) is between three and five hours, and it seems that this has remained fairly stable over the years. The decision delay (i.e. the time between the onset of symptoms and the first medical contact) is almost unanimously indicated as the major single component in the total delay. This represents around 40% of the pre-hospital phase. Transportation time appears to play only a slight role, if indeed any, in the total delay. Nonetheless, mobile coronary units have consistently shown that they can reduce thrombolysis time (e.g. the time between the onset of symptoms and the start of thrombolytic infusion) by almost 60 minutes, and this time-gain is comparable with the reduction in total delay obtained in Sweden with a media campaign. Strongly contrasting results were obtained from the analysis of the delay-determining factors.(ABSTRACT TRUNCATED AT 250 WORDS)

This report first describes the efficiency achieved by a large scale clinical trial (GISSI), which is widely recognized as having made an important contribution to the therapy of AMI, and second emphasizes how a comprehensive research project based upon an innovative clinical trial methodology can influence the attitude and the scientific productivity of a professional community operating within a national health system. To understand the methodology of GISSI, one must appreciate both the cultural and institutional setting in which the first GISSI trial took place as well as the strong economic and scientific expectation surrounding the second GISSI trial.

Blood stored in acid-citrate-dextrose (ACD) shows a progressive decrease in 2,3-diphosphoglycerate (DPG) content. Since the decrease in DPG increases hemoglobin oxygen affinity, which in turn may reduce tissue and venous PO2 and peripheral oxygen delivery, many efforts have been made to preserve or restore DPG levels in stored blood. An in vivo rejuvenating technique, employing fructose-1,6-diphosphate (FDP) at a mean dosage of 1 mmol kg-1 day-1 of phosphate, to increase the DPG circulating level in multi-transfused patients is proposed. Eighteen patients, who received at least one-third of their estimated blood volume (3990 +/- 480 (SEM) ml of ACD stored blood) in blood transfusion, were treated: nine with inorganic phosphate, and nine with FDP. Basal DPG was very low in both groups: 12.61 +/- 1.34 (SEM) and 10.42 +/- 0.98 (SEM) mumol g-1, respectively (normal value is 14.5 mumol g-1, at pH 7.40). However, DPG values increased significantly and promptly in patients receiving FDP, whereas in cases of inorganic phosphate administration, it was not significantly raised over the basal value until the third day. Phosphatemia remained normal and constant with FDP, but it rose significantly on the third day of treatment with inorganic phosphate. FDP appears to consistently and rapidly increase DPG levels after transfusion with blood stored in ACD, and to be particularly safe.

The 1-year prognosis of 293 patients discharged alive from the hospital after acute myocardial infarction (AMI), who experienced primary ventricular fibrillation (VF) in the acute phase, was compared with that of a reference group of 6,337 patients identified from the same population included in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico (GISSI) trial. There was no difference in the 6- and 12-month mortality between the patients with primary VF and the reference group (3.7 vs 2.7% and 4.1 vs 4.2%, respectively). Survival of the 2 groups was also similar when patients were stratified according to infarct site (anterior and posterior), and whether or not they received treatment with streptokinase during AMI. Thus, long-term mortality of patients discharged alive after AMI complicated by primary VF is low and is not influenced by previous fibrinolytic therapy or by infarct site. The excess mortality of patients with primary VF is confined to the hospital phase, after which survivors represent a low-risk subgroup.

The effect of a pre-operative high fibre diet on the resolution of ileus following cholecystectomy has been evaluated. The time needed to restore canalization of the gastro-intestinal tract has been compared in two random groups of patients (a total of thirty-eight) one treated with wheat bran and the other as control without the diet supplementation. The average persistence of ileus was 24 hours in the treated group and 54 hours in the control group. These results suggest that a bran-enriched diet could be an inexpensive and simple treatment to shorten the duration of ileus after abdominal surgery.

A dose-finding multicenter study was undertaken to evaluate the antiemetic efficacy of domperidone, an antidopaminergic drug, which has been proposed as a suitable alternative to high-dose metoclopramide in the control of cisplatin-induced nausea and vomiting. Forty-five patients were treated with different increasing high doses of domperidone (30, 60, 120 or 150 mg) administered by i.v. infusion over 20 min every 2 hr for a total of four doses for each patient, starting 30 min before chemotherapy. The number of episodes of emesis, the duration of nausea and vomiting and side-effects were recorded. Results do not suggest any specific difference in protective effect between the regimens tested. Moreover, occurrence of serious side-effects indicated that the safety of high-dose domperidone is doubtful.

Aim of the present study was to analyse the causes of death of the patients admitted to the G.I.S.S.I. Study. Clinical records of the 1386 in-hospital deaths were centrally analysed by two independent clinicians, who were not aware of the performed treatment and based their classification criteria upon clinical and anatomic data. Death causes were classified as follows: cardiac failure, electromechanical dissociation, cardiac rupture, sudden death and extracardiac deaths. Cardiac failure was the most frequent cause of mortality, as 725 pts out of the 1386 (52%) died from this complication in the whole group. 392 pts were part of the control group (6.7%), while 333 had received SK (5.6%): the difference was significant. No difference was observed between treated patients and control group for what concerns the remaining causes of death. Mortality from cardiac failure was strikingly reduced in a few groups of patients: females (from 11.4 down to 8.7%); age less than 65 years (from 4.1 down to 3.2%); early treated pts (up to 3 hrs): from 6.3 down to 5.2%; anterior location of AMI (9.2 down to 7.4%); first AMI episode (from 5.9 down to 4.7%). Such a reduction was remarkable for patients who remained alive after the 7th day from onset of symptoms: cardiac failure was the cause of death in 65 out of 5385 treated patients, and in 100 out of 5333 control group patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The in-hospital prognosis of patients with acute myocardial infarction complicated by primary ventricular fibrillation has not been satisfactorily defined. We addressed this question by studying patients with primary ventricular fibrillation derived from a large study (11,712 patients) of intravenous streptokinase in the treatment of acute myocardial infarction. Ventricular fibrillation was considered to be primary when it complicated a first myocardial infarction not associated with heart failure or shock and occurred within 48 hours of hospital admission. The 332 patients with primary ventricular fibrillation represented an overall incidence of 2.8 percent. A significant excess of in-hospital deaths was found in the patients with primary ventricular fibrillation as compared with those in the reference group (10.8 percent vs. 5.9 percent; relative risk, 1.94; 95 percent confidence interval, 1.35 to 2.78). Thrombolytic treatment with intravenous streptokinase did not afford protection against primary ventricular fibrillation. We observed that being over 65 years old had a protective effect against primary ventricular fibrillation (relative risk, 0.6; 95 percent confidence interval, 0.45 to 0.80). Our data do not indicate whether primary ventricular fibrillation is simply a marker for patients at increased risk of death or a direct cause of the increase in mortality. Our results do show, however, that primary ventricular fibrillation occurring in a coronary care unit is a negative predictor of short-term survival in patients with acute myocardial infarction.

Nizatidine is a new H2-receptor antagonist, as potent as ranitidine. It does not interfere with hepatic metabolism and it lacks anti-androgenic effects. An evening dose of 300 mg suppresses nocturnal acid secretion without diurnal carryover. Published clinical trials are limited. Over 3800 patients who have been treated with nizatidine, 300 mg for up to eight weeks or 150 mg at night for a year, did not appear to have significantly unexpected or unwanted side effects. Rate of healing for both duodenal and gastric ulcers and reduction in the rate of relapse are comparable to those of ranitidine.