Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.

BACKGROUND: Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described. METHODS: Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. RESULTS: A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). CONCLUSIONS: This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population.Clinical Trials.gov Registration NCT04568083.

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.

Specialty-related differences in the epidemiology, clinical profile, management and outcome of patients hospitalized for heart failure; the OSCUR study. Oucome dello Scompenso Cardiaco in relazione all'Utilizzo delle Risore.

AIMS: This study was designed to identify potential specialty-related differences in the epidemiology, clinical profile, management and outcome of patients hospitalized for congestive heart failure in departments of cardiology or internal medicine. METHODS AND RESULTS: From 1 July to 31 December 1998, we prospectively recorded epidemiological and clinical data from patients with congestive heart failure consecutively admitted to 11 departments of cardiology and 12 departments of internal medicine in Liguria, a northern area of Italy. The overall study population included 749 patients; 22% were treated by cardiologists and 78% by internists (P<0.0001). Patients managed by cardiologists were more likely to undergo echocardiography (92% vs 37%), Holter monitoring (25% vs 3%) and exercise stress testing (20% vs 0.5%) than those managed by internists (P=0.001). At discharge, patients treated by cardiologists were more likely to be prescribed beta-blockers (41% to 4%) and ACE inhibitors (100% to 74%) than those treated by internists (P<0.0001), and the latter medication at higher dosages by cardiologists than internists. In addition, patients followed by cardiologists were younger (70+/-9 to 79+/-1 years;P<0.0001), more likely to be male (61% to 50%;P=0.011) and to have coronary artery disease (57% to 45%;P<0.006) than those followed by internists. Conversely, patients followed by internists were more likely to have diabetes, chronic obstructive pulmonary disease, atrial fibrillation and renal failure (P<0.03). In the overall study population, 53 patients (7%) died during hospitalization. Patients treated by cardiologists had a mortality not significantly different from that of patients treated by internists (10% and 6%, respectively;P=0.067), although congestive heart failure was more severe on admission in patients treated by cardiologists. CONCLUSION: Cardiologists follow published guidelines for congestive heart failure more strictly than internists, but treat a smaller number of patients who are younger, have more severe congestive heart failure and fewer co-morbidities than those managed by internists.

Very early assessment of risk for in-hospital death among 11,483 patients with acute myocardial infarction. GISSI investigators.

BACKGROUND: The efficacy of reperfusion therapy after acute myocardial infarction is time dependent. The risk profile of every patient should be available as soon as possible. Our aim was to determine whether collection of simple clinical markers at hospital admission might allow reliable risk stratification for in-hospital mortality. METHODS: The subjects were 11,483 patients with acute myocardial infarction from the GISSI-2 cohort. The GISSI-1 and GISSI-3 populations were selected to validate the classification. To stratify patients, the tree-growing method called recursive partitioning and amalgamation (RECPAM) was used. This method is used to identify homogeneous and distinct subgroups with respect to outcome. RESULTS: The RECPAM algorithm provided 6 classes. RECPAM class I included Killip class 3 to class 4 patients (516 deaths/1000). RECPAM class II included Killip 2 patients older than 66 years and with anterior infarction or sites of infarction that could not be evaluated (314 deaths/1000). Killip 1 patients older than 75 years and with anterior or multiple sites or sites that could not be evaluated were included in RECPAM class III with Killip class 2 patients younger than 66 years and with systolic blood pressure less than 120 mm Hg or older than 66 years and with any other infarction site (207 deaths/1000). The other classes showed lower mortality rates (91, 32, and 12 deaths/1000 for RECPAM classes IV, V, and VI). In the GISSI 1 and GISSI 3 samples the 6 classes ranked in the same order in terms of mortality rate. With respect to low-risk strata, patients belonging to RECPAM class VI without serious clinical events in the first 4 days had a very low incidence of in-hospital death (0.9%) or morbidity. Cumulative 6-month mortality for the 6 RECPAM classes was 59.6%, 41.2%, 26.4%, 12.9%, 4. 8%, and 2.2%. CONCLUSIONS: Four simple clinical markers readily available at admission of patients with myocardial infarction allow a quick, reliable, and inexpensive prediction of risk for in-hospital and 6-month mortality. The RECPAM classification also helped identify a large subgroup of patients fit for early hospital discharge.

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.

Individual risk assessment for intracranial haemorrhage during thrombolytic therapy.

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.