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.

Risk-associated management disparities in acute myocardial infarction.

Despite improvements in the treatment of myocardial infarction (MI), risk-associated management disparities may exist. We investigated this issue including temporal trends in a large MI cohort (n = 179,291) registered 2005-2017 in SWEDEHEART. Multivariable models were used to study the associations between risk categories according to the GRACE 2.0 score and coronary procedures (timely reperfusion, invasive assessment ≤ 3 days, in-hospital coronary revascularization), pharmacological treatments (P2Y12-blockers, betablockers, renin-angiotensin-aldosterone-system [RAAS]-inhibitors, statins), structured follow-up and secondary prevention (smoking cessation, physical exercise training). High-risk patients (n = 76,295 [42.6%]) experienced less frequent medical interventions compared to low/intermediate-risk patients apart from betablocker treatment. Overall, intervention rates increased over time with more pronounced increases seen in high-risk patients compared to lower-risk patients for in-hospital coronary revascularization (+ 23.6% vs. + 12.5% in patients < 80 years) and medication with P2Y12-blockers (+ 22.2% vs. + 7.8%). However, less pronounced temporal increases were noted in high-risk patients for medication with RAAS-blockers (+ 8.5% vs. + 13.0%) and structured follow-up (+ 31.6% vs. + 36.3%); pinteraction < 0.001 for all. In conclusion, management of high-risk patients with MI is improving. However, the lower rates of follow-up and of RAAS-inhibitor prescription are a concern. Our data emphasize the need of continuous quality improvement initiatives.

Myocardial infarction in diffuse large B-cell lymphoma patients - a population-based matched cohort study.

BACKGROUND: The outcome for diffuse large B-cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R-CHOP. An increased rate of heart failure is well documented following this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known. METHOD: We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma-free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population-based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models. RESULTS: Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14-1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10-2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01-1.64). Among younger patients (≤70), a short-term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30-day survival among patients and comparators. CONCLUSION: DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival.

Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

Morbidity and cause-specific mortality in first-time myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA. METHODS: This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69 267 patients with first-time MI-CAD. RESULTS: Almost all event rates (median follow-up 3.8 years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n = 268 (6.6%), n = 1563 (21.5%), n = 17 777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk. CONCLUSIONS: Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.

Predictors of adverse outcome in patients with myocardial infarction with non-obstructive coronary artery (MINOCA) disease.

BACKGROUND: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCAs) is an increasingly recognized entity. No previous study has evaluated predictors for new major adverse cardiacvascular events (MACEs) and death in patients with MINOCA. METHODS: We conducted an observational study of MINOCA patients recorded between July 2003 and June 2013 and followed until December 2013 for outcome events. Out of 199,163 MI admissions, 9092 consecutive unique patients with MINOCA were identified. The mean age was 65.5 years and 62% were women. MACE was defined as all-cause mortality, rehospitalization for acute MI, ischemic stroke and heart failure. Hazard ratio and 95% confidence interval (HR; 95% CI) was calculated using Cox-regression. RESULTS: A total of 2147 patients (24%) experienced a new MACE and 1254 patients (14%) died during the mean follow-up of 4.5 years. Independent predictors for MACE after adjustment, were older age (1.05; 1.04-1.06), diabetes (1.44; 1.21-1.70), hypertension (1.25; 1.09-1.43), current smoking (1.38; 1.15-1.66), previous myocardial infarction (1.38; 1.04-2.82), previous stroke (1.69; 1.35-2.11), peripheral vascular disease (1.55; 1.97-2.23), chronic obstructive pulmonary disease (1.63; 1.32-2.00), reduced left ventricular ejection fraction (2.00; 1.54-2.60), lower level of total cholesterol (0.88; 0.83-0.94) and higher level of creatinine (1.01; 1.00-1.03). Independent predictors for all cause death were age, current smoking, diabetes, cancer, chronic obstructive pulmonary disease, previous stroke, reduced left ventricular fraction, lower level of total cholesterol and higher levels of creatinine and CRP. CONCLUSIONS: The clinical factors predicting new MACE and death of MINOCA patients seem to be strikingly similar to factors previously shown to predict new cardiovascular events in patients with MI and obstructive coronary artery disease.

Higher mortality after myocardial infarction in patients with severe mental illness: a nationwide cohort study.

OBJECTIVES: The aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival and determine the influence of risk factor burden, myocardial infarction severity and different treatments. DESIGN, SETTING AND PARTICIPANTS: This population-based cohort study, conducted in Sweden during the period 1997-2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n = 209 592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment. MAIN OUTCOME MEASURES: The outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers. RESULTS: Patients with bipolar disorder (n = 442) and schizophrenia (n = 541) were younger (mean age 68 and 63 years, respectively) than those without SMI (n = 208 609; mean age 71 years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55-2.56] and 1-year mortality (OR 2.11, 95% CI 1.74-2.56) in the fully adjusted model. The highest mortality was observed amongst patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88-3.54; 1-year mortality: OR 2.55, 95% CI 1.98-3.29). CONCLUSION: SMI is associated with a markedly higher mortality after myocardial infarction, also after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.

International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom, Sweden, and the United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry-GWTG/NCDR registries.

OBJECTIVES: To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. BACKGROUND: Results from clinical trials suggest significant variation in care across the world. However, international comparisons in "real world" registries are limited. METHODS: We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n=137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n=45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n=147,438] clinical registries. RESULTS: Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). CONCLUSIONS: The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement.

ST depression in ECG at entry indicates severe coronary lesions and large benefits of an early invasive treatment strategy in unstable coronary artery disease; the FRISC II ECG substudy. The Fast Revascularisation during InStability in Coronary artery disease.

BACKGROUND: In unstable coronary artery disease, ST-segment depression indicates a poor prognosis. We evaluated whether the effect of early revascularization and the extent of coronary lesions were related to ST-segment and T wave changes on admission. METHODS AND RESULTS: 2457 patients with unstable coronary artery disease were randomized to an early invasive strategy with coronary angiography/revascularization within 7 days or to a non-invasive strategy with coronary procedures only when symptoms or severe ischaemia recurred. ST depression was present in 1114 (45.5%) patients. In the invasive group, 45% of the patients with ST depression had three-vessel disease or left main stenosis compared with 22% if no ST-segment depression was present, PP=0.004 while mortality was changed from 5.8 to 3.3%, P=0.050. In patients without ST-segment depression the corresponding rates concerning death/myocardial infarction were 10.4 and 8.9, and for mortality 2.0 and 1.2% (non-significant). CONCLUSIONS: In unstable coronary artery disease, ST-segment depression is associated with a 100% increase in the occurrence of three-vessel/left main disease and to an increased risk of subsequent cardiac events. In these patients an early invasive strategy substantially decreases death/myocardial infarction.