Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor has been the mainstay of therapy for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) following percutaneous coronary intervention (PCI) for more than two decades. Over this period, numerous trials have evaluated different antiplatelet strategies, initially focusing on more effective and prolonged regimens, and more recently on decreasing the intensity or duration of DAPT. Despite a wealth of accumulated evidence, the optimal antiplatelet strategy-including the ideal agent, combination, or treatment duration-remains a subject of active debate. This review summarizes the evolution of antiplatelet therapy, with particular emphasis on randomized controlled trials of DAPT in patients with ACS or CCS undergoing PCI.

Background Both Takotsubo syndrome (TS) and ST-elevation myocardial infarction (STEMI) are conditions characterised by the acute onset of left ventricular (LV) dysfunction. While LV thrombus is a known complication of LV dysfunction, its epidemiology in these two patient groups remains poorly understood.Methods We used data from the Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) study, which prospectively enrolled patients with TS and STEMI at Sahlgrenska University Hospital. Serial echocardiography was performed on admission and on days 1, 2, 3, 7, 14 and 30. Predictors of LV thrombus were identified using Cox regression analyses.Results 314 patients were included; 68 with TS, 148 with anterior STEMI and 98 with non-anterior STEMI. Mean LV ejection fraction (LVEF) at admission was 39% (95% CI 35.8 to 42.2) in TS, 46.7% (95% CI 43.3 to 50.1) in anterior STEMI and 52.8% (95% CI 48.9 to 56.7) in non-anterior STEMI. LV thrombus occurred in 20 of 246 (8.1%) STEMI patients but in none of the TS patients. All but one LV thrombus was found in anterior STEMI. All LV thrombi in anterior STEMI were detected within 7 days, while the single non-anterior LV thrombus was found on day 30. All patients with LV thrombi received anticoagulation. Predictors of LV thrombus included lower LVEF and higher troponin levels.Conclusions Despite more severe LV dysfunction in TS compared with STEMI, LV thrombus was exclusively found in STEMI patients. Almost all LV thrombi were found in anterior STEMI within the first week and showed a high-resolution rate at 30 days. Our findings highlight pathophysiological differences between these two conditions, warranting further investigation and implications for differing surveillance needs after TS and STEMI.

BACKGROUND:Accurate assessment of mortality, bleeding, and atherothrombotic risk in patients with cancer and acute coronary syndrome could inform novel personalised treatment strategies, but no standardised tools for this purpose exist. We aimed to develop and validate a clinically applicable risk score for mortality, bleeding, and ischaemic events in patients with cancer and acute coronary syndrome. METHODS:In this model development and validation study, we obtained data for 1 017 759 patients who presented with acute coronary syndrome in England, UK (n=815 170; 36 771 with cancer), Sweden (n=194 059; 10 262 with cancer), and Switzerland (n=8530; 203 with cancer) between Jan 1, 2004, and Aug 8, 2023. Machine learning models were developed to predict all-cause mortality, major bleeding events, and ischaemic events, defined as a composite of cardiovascular death, myocardial infarction, and ischaemic stroke, in patients with cancer and acute coronary syndrome from England in a competing risks framework with a prediction horizon of 6 months. Final models (the ONCO-ACS score) were externally validated in geographically distinct held out datasets from the English Midlands, Sweden, and Switzerland. FINDINGS:Patients with cancer and with acute coronary syndrome were characterised by high rates of mortality (cumulative incidence 27·8% [95% CI 27·3-28·3]), major bleeding (7·3% [7·0-7·5]), and ischaemic events (16·1% [15·7-16·4]) and had a distinct risk profile. The ONCO-ACS score was informed by a single set of variables: tumour type, time since cancer diagnosis, metastatic disease, age, haemoglobin, heart rate, estimated glomerular filtration rate, BMI, Killip class, cardiac arrest, and major bleed within 6 months. Accounting for traditional and cancer-related risk factors, ONCO-ACS showed a time-dependent area under the receiver operating characteristic curve (tAUC) at 6 months of 0·84 (0·83-0·85) for all-cause mortality, 0·70 (0·68-0·73) for major bleeding, and 0·79 (0·78-0·81) for ischaemic events on internal validation. On external validation, ONCO-ACS achieved similar performance for all-cause mortality (tAUC at 6 months 0·84 [0·82-0·85] for the English Midlands, 0·80 [0·79-0·82] for Sweden, and 0·83 [0·76-0·91] for Switzerland), major bleeding events (0·70 [0·67-0·74] for the English Midlands, 0·67 [0·65-0·70] for Sweden, and 0·74 [0·57-0·91] for Switzerland), and ischaemic events (0·76 [0·74-0·78] for the English Midlands, 0·70 [0·69-0·72] for Sweden, and 0·73 [0·61-0·86] for Switzerland). ONCO-ACS was well calibrated and decision curve analyses suggested favourable clinical utility. Applying ONCO-ACS to current guidelines suggests that most patients with cancer and acute coronary syndrome qualify for invasive management and long dual antiplatelet therapy using clopidogrel. INTERPRETATION:The ONCO-ACS score provides a validated practical tool for predicting mortality, bleeding, and ischaemic risk in patients with cancer and acute coronary syndrome. Combined assessment of competing outcome risks could facilitate balancing treatment benefits and harms. FUNDING:British Heart Foundation, Cancer Research UK, Swiss Heart Foundation, University of Zurich Foundation, Kurt-Senta-Herrmann Foundation, Theodor-Ida-Herzog-Egli Foundation, Foundation for Cardiovascular Research-Zurich Heart House, Swedish ALF Research Funds.

BACKGROUND:Reperfusion by mechanical thrombectomy (MT) is an alternative for reperfusion in acute pulmonary embolism (PE) when systemic thrombolysis (ST) is contraindicated or has failed. OBJECTIVES:This study evaluated the early experience from MT in Sweden with comparison with that of ST. METHODS:We included all adult patients treated with large-bore MT in Sweden from January of the year the technique was introduced until December 2023, as well as patients concurrently treated with ST in the respective hospitals. The primary outcome was a composite of early death or severe bleeding. RESULTS:During the study period, MT was performed exclusively with the FlowTriever (FT) system. Among 132 patients included in 7 hospitals, 61 patients aged 67 ± 15 years were treated with FT only and 61 aged 68 ± 14 years with ST only. High-risk PE was present in 32 patients in the FT group and 38 in the ST group. All other patients had intermediate high-risk PE. There were 6 primary outcome events in the FT group and 17 in the ST group (adjusted odds ratio [OR], 0.19; 95% CI, 0.05-0.69). Five (8%) patients in the FT group and 13 (21%) in the ST group died within 30 days (OR, 0.33; 95% CI, 0.11-0.99). One severe bleeding occurred after FT and 7 after ST (OR, 0.18; 95% CI, 0.03-1.10). CONCLUSION:MT, using the FT system, in high-risk and intermediate high-risk PE was effective and possibly safer than reperfusion with ST.

AIMS:Acute myocardial infarction (AMI) is associated with significant loss-of-life expectancy, particularly among younger females. Addressing risk factors is crucial for optimizing prevention strategies. The aim of this study was to describe the trends in risk factors and clinical outcomes in a nationwide cohort of young AMI patients stratified by sex. METHODS AND RESULTS:Using Swedish registries, we included AMI patients aged 18-59 and selected five matched non-AMI controls from the general population. Risk factors included hypertension, diabetes, chronic kidney disease, hyperlipidaemia, obesity, smoking and systemic inflammatory disease. Clinical outcomes were major adverse cardiovascular events (death, AMI, stroke, or heart failure) and bleeding events. From 2006 to 2021, 44 254 AMI cases (9602 females and 34 652 males) and 220 721 non-AMI controls (47 967 females and 172 754 males) were included. Among AMI cases, the prevalence of at least one risk factor was higher in females than males (78.9 vs. 73.7%). Obesity increased from 25.2 to 35.5% becoming the most common risk factor. The risk of clinical outcomes was higher in cases than controls and in females compared with males among the cases, but lower among females compared with males among the controls. Five-year mortality was 6.1 vs. 1.3% in females and 4.9 vs. 1.8% males (cases vs. controls). CONCLUSION:Three in four young AMI patients have at least one known risk factor, of which obesity is the most common. Risk factor burden and clinical outcomes are worse among females. Prevention strategies and enhanced follow-up for young AMI patients should be prioritized. Further studies are needed to investigate sex-specific risk factors.

The European Society of Cardiology has released new 2024 guidelines on chronic coronary syndrome. These guidelines emphasize that patients with this condition should be actively assessed and treated to reduce the risk of future events. Key updates include the introduction of a risk factor-based clinical probability model to aid in this process. Furthermore, the guidelines stress that coronary CT angiography is recommended as the first-line diagnostic method for patients with a low to moderate probability of coronary artery disease. In cases of moderate to high probability, functional tests such as stress echocardiography, PET-CT, or perfusion MRI are advised, depending on availability. The guidelines recommend that all patients with chronic coronary artery disease receive high-intensity lipid-lowering treatment, with a target LDL level of less than 1.4 mmol/L. For patients with non-obstructive coronary artery disease who continue to experience persistent angina pectoris, further investigation of the microcirculation is recommended.

BACKGROUND:The Global Registry of Acute Coronary Events (GRACE) scoring system guides the management of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) according to current guidelines. However, broad validation of the sex-specific GRACE 3.0 in-hospital mortality model, and corresponding models for predicting long-term mortality and the personalised effect of early invasive management, are still needed. METHODS:We used data of 609 063 patients with NSTE-ACS from ten countries between Jan 1, 2005, and June 24, 2024. A machine learning model for 1-year mortality was developed in 400 054 patients from England, Wales, and Northern Ireland. Both the in-hospital mortality model and the new 1-year mortality model were externally validated in patients from Sweden, Switzerland, Germany, Denmark, Spain, the Netherlands, and Czechia. A separate machine learning model to predict the individualised effect of early versus delayed invasive coronary angiography and revascularisation on a composite primary outcome of all-cause death, non-fatal recurrent myocardial infarction, hospital admission for refractory myocardial ischaemia, or hospital admission for heart failure at a median follow-up of 4·3 years was developed and externally validated in participants from geographically different sets of hospitals in the Danish VERDICT trial. FINDINGS:The in-hospital mortality model (area under the receiver operating characteristic curve [AUC] 0·90, 95% CI 0·89-0·91) and the 1-year mortality model (time-dependent AUC 0·84, 95% CI 0·82-0·86) showed excellent discriminative abilities on external validation across all countries. Both models were well calibrated and decision curve analyses suggested favourable clinical utility. Compared with score version 2.0, both models provided improved discrimination and risk reclassification. The individualised treatment effect model effectively identified patients who would benefit from early invasive management on external validation. Patients with high predicted benefit had reduced risk of the composite outcome when randomly assigned to early invasive management (hazard ratio 0·60, 95% CI 0·41-0·88), whereas patients with no-to-moderate predicted benefit did not (1·06, 0·80-1·40; pinteraction=0·014). The individualised treatment effect model suggested that the group of patients with NSTE-ACS who benefit from early intervention might be incompletely captured by current treatment strategies. INTERPRETATION:The updated GRACE 3.0 scoring system provides a validated, practical tool to support personalised risk assessment in patients with NSTE-ACS. Prediction of an individual's long-term cardiovascular benefit from early invasive management could refine future trial design. FUNDING:Swiss Heart Foundation, University of Zurich Foundation, Kurt and Senta Herrmann Foundation, Theodor and Ida Herzog-Egli Foundation, and Foundation for Cardiovascular Research-Zurich Heart House.

Background The aim of the ARC-HBR (Academic Research Consortium for High Bleeding Risk) and PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score definitions for high bleeding risk is to identify patients who would benefit from shorter or less intensive antiplatelet therapy after coronary stenting. Objectives The aim of this study was to assess the performance of the ARC-HBR and PRECISE-DAPT score definitions for high bleeding risk in routine clinical practice. Methods Using nationwide registers, all patients in Stockholm, Sweden, who were discharged after coronary stenting with dual antiplatelet therapy (January 1, 2013, to July 1, 2018) were included. Patients were categorized as high bleeding risk according to the 2 risk tools, and risk for bleeding (BARC [Bleeding Academic Research Consortium] types 3-5 or TIMI major or minor) and ischemic events (myocardial infarction or ischemic stroke) within 1 year after discharge was assessed. Results Of 7,562 patients, the proportions categorized as high bleeding risk were 27% (2,004 of 7,562) using the ARC-HBR definition and 38% (2,894 of 7,562) using the PRECISE-DAPT score; 22% (1,696 of 7,562) had discordant categorization of high bleeding risk comparing the 2 risk tools. Patients with vs without high bleeding risk according to the ARC-HBR definition had higher risk for BARC type 3 to 5 bleeding (1-year risk 7.1% vs 2.3%; HR: 3.21; 95% CI: 2.47-4.17) and ischemic events (7.8% vs 2.8%; HR: 2.96; 95% CI: 2.31-3.79). Patients with vs without high bleeding risk according to the PRECISE-DAPT score had higher risk for TIMI major or minor bleeding (4.4% vs 2.1%; HR: 2.17; 95% CI: 1.63-2.89) and ischemic events (6.2% vs 2.7%; HR: 2.38; 95% CI: 1.85-3.05). The PRECISE-DAPT score underestimated bleeding risk across almost all score levels (median absolute difference between observed and predicted 1-year risk 1.1%; Q1-Q3: 0.8%-1.4%). Conclusions There was substantial discordance in the categorization of high bleeding risk between the ARC-HBR definition and the PRECISE-DAPT score. Both tools identified patients at increased bleeding risk, but those patients also had increased ischemic risk. The PRECISE-DAPT score underestimated bleeding risk. Guideline-recommended high bleeding risk definitions may not be generalizable across patient populations, and refined scoring systems are needed.

Background: The aim of this study was to evaluate the implementation of a novel extra corporeal cardiopulmonary (ECPR) program in the greater Stockholm area with focus on feasibility, safety aspects and clinical outcomes. Methods: Prospective observational study of ECPR program including patients with OHCA from January 2020 to December 2022, fulfilling ECPR criteria: age 18-65 years, initial shockable rhythm or pulseless electrical activity, witnessed arrest, bystander cardiopulmonary resuscitation and refractory arrest after three cycles of advance cardiac life support. The predefined time threshold from collapse to extracorporeal membrane oxygenation (ECMO) initiation was set at 60 min. Results: We included 95 patients. Of these, 22/95 (23%) had return of spontaneous circulation before ECMO initiation, 39/95 (41%) were excluded for ECMO and 34/95 (36%) had ECMO initiated out of which 23 patients were admitted alive to the ICU. ECMO-initiation within 60 min was met in 9%. In 6 patients vascular access was complicated, 2 patients had severe bleeding at access site requiring intervention. Survival to discharge among all cases was 25% (24/95). Among patients admitted to ICU on ECMO 39% (9/23) survived to discharge, of these 78% had cerebral performance category scale score 1-2 within 12 months. 8 out of 9 survivors had time from OHCA to ECMO-initiation >60 min. Conclusion: The implementation of an ECPR protocol was feasible without any major, unexpected safety aspects but did not meet the intended target time intervals. Despite this, survival rates were similar to previous studies although most survivors had >60 min to ECMO-initiation.

BACKGROUND: The effect of myocardial infarction (MI) on life expectancy is difficult to study because the prevalence of MI hinders direct comparison with the life expectancy of the general population. We sought to assess this in relation to age, sex, and left ventricular ejection fraction (LVEF) by comparing individuals with MI with matched comparators without previous MI. METHODS: We included patients with a first MI between 1991 and 2022 from the nationwide SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), each matched with up to 5 comparators on age, sex, and region of residence. Flexible parametric survival models were used to estimate excess mortality and mean loss of life expectancy (LOLE) depending on index year, age, sex, and LVEF, and adjusted for differences in characteristics. RESULTS :A total of 335 748 cases were matched to 1 625 396 comparators. A higher LOLE was observed in younger individuals, women, and those with reduced LVEF (<50%). In 2022, the unadjusted and adjusted mean LOLE spanned from 11.1 and 9.5 years in 50-year-old women with reduced LVEF to 5 and 3.7 months in 80-year-old men with preserved LVEF. Between 1992 and 2022, the adjusted mean LOLE decreased by 36% to 55%: from 4.4 to 2.0 years and from 3.3 to 1.9 years in 50-year-old women and men, respectively, and from 1.7 to 1.0 years and from 1.4 to 0.9 years in 80-year-old women and men, respectively. CONCLUSIONS: LOLE is higher in younger individuals, women, and those with reduced LVEF, but is attenuated when adjusting for comorbidities and risk factors. Advances in MI treatment during the past 30 years have almost halved LOLE, with no clear sign of leveling off to a plateau.

AIMS:Of all spontaneous bleeding complications in patients with acute myocardial infarction (MI), upper gastrointestinal bleeding (UGIB) is common and of specific interest since it could be prevented by several prophylactic measures. We aimed to determine the incidence, associated outcomes, and predictors of UGIB following acute MI. METHODS AND RESULTS:All patients with acute MI enrolled in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry from January 2007 to June 2016 and discharged alive on any antithrombotic therapy (n = 149 477) were followed regarding UGIB for 1 year. Associated outcomes were determined by Cox proportional hazards regression with UGIB as a time-dependent covariate, adjusting for baseline characteristics, invasive treatment, and medical treatment at discharge. Predictors of UGIB were determined by logistic regression and machine learning models.At 1 year, UGIB had occurred in 2230 patients (cumulative incidence 1.5%) and was significantly associated with an increased risk of all-cause death [hazard ratio (HR) 2.86, 95% confidence interval (CI) 2.58-3.16] and stroke (HR 1.80, 95% CI 1.32-2.45) but not with recurrent MI (HR 1.17, 95% CI 0.97-1.42). The most important predictors of UGIB were haemoglobin, age, systolic blood pressure, blood glucose, smoking status, previous upper gastrointestinal bleeding, and antithrombotic and gastroprotective treatment. CONCLUSION:After acute MI, readmission because of UGIB is common and significantly associated with poor prognosis. By using machine learning in addition to traditional logistic regression, new predictors of UGIB, such as blood glucose and smoking status, were identified.

New guidelines from the European Society of Cardiology (ESC) for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (NSTEMI-ACS) stress the importance of more individualized diagnostics and therapy based on the patients' initial risk profile balancing risk of ischemia with risk of bleeding. In this commentary, the Working Group on Coronary Artery Disease of the Swedish Society of Cardiology points out what is new in the 2020 NSTEMI guidelines.

New guidelines from the European Society of Cardiology (ESC) for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (NSTEMI-ACS) stress the importance of more individualized diagnostics and therapy based on the patients' initial risk profile balancing risk of ischemia with risk of bleeding. In this commentary, the Working Group on Coronary Artery Disease of the Swedish Society of Cardiology points out what is new in the 2020 NSTEMI guidelines.

Background Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in‐hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results From the nationwide SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Ad verse Outcomes With Early Implementation of the ACC /AHA Guidelines) scores. Internal and temporal validity was assessed. In‐hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and C‐reactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall ( C ‐index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions The 5‐item SWEDEHEART score discriminates in‐hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores.

Aims To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population. Methods and results Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%. Conclusion During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.

Background: QRS ≥ 120 ms is present in 1/3 of patients with heart failure with reduced ejection fraction, favorably treated with cardiac resynchronization therapy. In heart failure with preserved ejection fraction (HFPEF), the prevalence of and correlates with QRS prolongation are largely unknown. Methods: KaRen is a multicenter prospective registry of HFPEF (ClinicalTrials.gov NCT00774709 ). Inclusion criteria are Framingham symptoms and signs of heart failure together with NT-proBNP >300 ng/L and LVEF ≥45%. In patients with sinus rhythm and with atrial fibrillation / flutter (AF), the prevalence of and association between QRS prolongation and clinical characteristics was assessed with uni- and multivariable linear regression, with 10 clinical variables, ejection fraction, and EKG parameters (10 in sinus rhythm; 6 in AF), using backward step-wise selection based on p < 0.10. Results: We studied 382 patients, mean (SD) age 77 (9) years, 56% women. QRS < 120 ms, 120-149 ms, ≥ 150 ms, LBBB, and ventricular-paced EKG was present in 78, 11, 3, 3 and 8% respectively. One-hundred twenty-six patients (35%) had AF. AF was not associated with QRS width. The table lists variables independently associated with QRS in ms, their baseline values and Beta coefficients, separately among patients in sinus rhythm and AF, excluding ventricular-paced patients. Conclusions: In HFPEF, QRS prolongation and LBBB are less common than in reduced ejection fraction. QRS prolongation is associated with other EKG pathology and with B-blocker use. The rarely measured parameter “P-wave duration” may reflect the same underlying global conduction delay as QRS duration.