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Aims The benefits of nationwide screening and tailored health guidance on improving obesity and cardiovascular risk factors is uncertain. The aim of the present study was to investigate the association of the national health screening and tailored health guidance with population health outcomes. Methods and results A fuzzy regression discontinuity design analysed data of men and women aged 40–74 years who participated in a nationwide health screening programme in Japan from 1 April 2008 to 31 March 2019 and were recorded in the Japanese National Database. Exposure was assignment to the national health guidance of counselling on healthy lifestyle and clinical follow-up for individuals found to have waist circumference ≥85 cm for men ≥90 cm for women with one or more cardiovascular risk factors during annual national health screening. The primary outcomes were changes in obesity status and cardiovascular risk factors 1 year after screening. Of 3 490 112 men and 2 328 929 women, the assignment to the health guidance resulted in small reductions in obesity parameters: waist circumference; men, −0.27 cm [95% confidence interval (CI) −0.29 to −0.26]; women −0.34 (−0.41 to −0.27); body mass index, −0.07 kg/m2 (−0.075 to −0.066); −0.11 kg/m2 (−0.13 to −0.10); weight, −0.21 kg (−0.22 to −0.19); −0.28 kg (−0.32 to −0.24) that attenuated over time. Short-term improvements were also observed in blood pressure, haemoglobin A1c, fasting glucose and triglycerides across both sexes. Conclusion A nationwide health screening programme was associated with only small, and transient improvements in obesity and cardiovascular risk factors.

Aims The effect of the COVID-19 pandemic on care and outcomes across non-COVID-19 cardiovascular (CV) diseases is unknown. A systematic review and meta-analysis was performed to quantify the effect and investigate for variation by CV disease, geographic region, country income classification and the time course of the pandemic. Methods and results From January 2019 to December 2021, Medline and Embase databases were searched for observational studies comparing a pandemic and pre-pandemic period with relation to CV disease hospitalisations, diagnostic and interventional procedures, outpatient consultations, and mortality. Observational data were synthesised by incidence rate ratios (IRR) and risk ratios (RR) for binary outcomes and weighted mean differences for continuous outcomes with 95% confidence intervals. The study was registered with PROSPERO (CRD42021265930). A total of 158 studies, covering 49 countries and 6 continents, were used for quantitative synthesis. Most studies (80%) reported information for high-income countries (HICs). Across all CV disease and geographies there were fewer hospitalisations, diagnostic and interventional procedures, and outpatient consultations during the pandemic. By meta-regression, in low-middle income countries (LMICs) compared to HICs the decline in ST-segment elevation myocardial infarction (STEMI) hospitalisations (RR 0.79, 95% confidence interval [CI] 0.66–0.94) and revascularisation (RR 0.73, 95% CI 0.62–0.87) was more severe. In LMICs, but not HICs, in-hospital mortality increased for STEMI (RR 1.22, 95% CI 1.10–1.37) and heart failure (RR 1.08, 95% CI 1.04–1.12). The magnitude of decline in hospitalisations for CV diseases did not differ between the first and second wave. Conclusions There was substantial global collateral CV damage during the COVID-19 pandemic with disparity in severity by country income classification.

Aims The optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis. Methods and results A systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78–1.04], MI (RR: 0.86, 95% CI: 0.63–1.16), admission for HF (RR: 0.66, 95% CI: 0.43–1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88–1.23), major bleeding (RR: 0.86, 95% CI: 0.68–1.09), or stroke (RR: 0.95, 95% CI: 0.59–1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40–0.81) and length of stay (median difference: −22 h, 95% CI: −36.7 to −7.5 h) were reduced with an early IS. Conclusion In all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS.

Standardized data definitions are essential for monitoring and benchmarking the quality of care and patient outcomes in observational studies and randomized controlled trials. There are no contemporary pan-European data standards for the acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aimed to develop such data standards for ACS and PCI. Following a systematic review of the literature on ACS and PCI data standards and evaluation of contemporary ACS and PCI registries, we undertook a modified Delphi process involving clinical and registry experts from 11 European countries, as well as representatives from relevant ESC Associations, including the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Acute CardioVascular Care (ACVC). This resulted in final sets of 68 and 84 ‘mandatory’ variables and several catalogues of optional variables for ACS and PCI, respectively. Data definitions were provided for these variables, which have been programmed as the basis for continuous registration of individual patient data in the online EuroHeart IT platform. By means of a structured process and the interaction with major stakeholders, internationally harmonized data standards for ACS and PCI have been developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies.

AimsTo assess processes of care and clinical outcomes in cancer patients with ST elevation myocardial infarction (STEMI) according to cancer type.Methods and resultsThis is a national population-based study of patients admitted with STEMI in the UK between January 2005 and March 2019. Data were obtained from the National Heart Attack Myocardial Infarction National Audit Project (MINAP) registry and the Hospital Episode Statistics registry. We identified 353 448 STEMI-indexed admissions between 2005 and 2019. Of those, 8581 (2.4%) had active cancer. Prostate cancer (29% of STEMI patients with cancer) was the most common cancer followed by haematologic malignancies (14%) and lung cancer (13%). Cancer patients were less likely to receive invasive coronary revascularization (60.0% vs. 71.6%, P ConclusionSTEMI patients with cancer have a higher risk of short- and long-term mortality, particularly lung cancer. Colon cancer is the main cancer associated with major bleeding. Cardiovascular disease was the main cause of death in the first month, whereas cancer was the main cause of death within 1 year.

Aims This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries. Methods and results Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, leftsided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures. Conclusion Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries.

Aims The importance of standard modifiable cardiovascular risk factors (SMuRFs) in preventing non-ST-segment elevation myocardial infarction (NSTEMI) is established. However, NSTEMI may present in the absence of SMuRFs, and little is known about their outcomes. Methods and results We analysed 176 083 adult (≥18 years) hospitalizations with NSTEMI using data from the United Kingdom (UK) Myocardial Infarction National Audit Project (MINAP). Clinical characteristics and all-cause in-hospital mortality were analysed according to SMuRF status, with 135 223 patients presenting with at least one of diabetes, hypertension, hypercholesterolaemia, or current smoking status and 40 860 patients without any SMuRFs. Those with a history of coronary artery disease were excluded. Patients without SMuRFs were more frequently older (median age 72 year vs. 71 years, P Conclusion More than one in five patients presenting with NSTEMI had no SMuRFs, who were less frequently received guideline-recommended management and had lower in-hospital (all-cause and cardiac) mortality and MACE than patients with SMuRFs.

Aims Little is known about the association between the type of admission ward and quality of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results We analysed data from 337 155 NSTEMI admissions between 2010 and 2017 in the UK Myocardial Ischaemia National Audit Project (MINAP) database. The cohort was dichotomised according to receipt of care either on a medical (n = 142,876) or cardiac ward, inclusive of acute cardiac wards and cardiac care unit (n = 194,279) on admission to hospital. Patients admitted to a cardiac ward were younger (median age 70 y vs. 75 y, P Conclusion Patients with NSTEMI admitted to a cardiac ward on admission were more likely to receive guideline directed management and had better clinical outcomes.

Aims To establish a set of quality indicators (QIs) for the cardiovascular (CV) assessment and management of patients undergoing non-cardiac surgery (NCS). Methods and results The Quality Indicator Committee of the European Society of Cardiology (ESC) and European Society of Anaesthesiology and Intensive Care (ESAIC) in collaboration with Task Force members of the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS followed the ESC methodology for QI development. This included (1) identification, by constructing a conceptual framework of care, of domains of the CV assessment, and management of patients with risk factors or established cardiovascular disease (CVD) who are considered for or undergoing NCS, (2) development of candidate QIs following a systematic literature review, (3) selection of the final set of QIs using a modified Delphi method, and (4) evaluation of the feasibility of the developed QIs. In total, eight main and nine secondary QIs were selected across six domains: (1) structural framework (written policy), (2) patient education and quality of life (CV risk discussion), (3) peri-operative risk assessment (indication for diagnostic tests), (4) peri-operative risk mitigation (use of hospital therapies), (5) follow-up (post-discharge assessment), and (6) outcomes (major CV events). Conclusion We present the 2022 ESC/ESAIC QIs for the CV assessment and management of patients with risk factors or established CVD who are considered for or are undergoing NCS y. These indicators are supported by evidence from the literature, underpinned by expert consensus, and align with the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS.

Aims Little is known about ethnic disparities in care and clinical outcomes of patients admitted with non-ST-segment elevation myocardial infarction (NSTEMI) in national cohorts from universal healthcare systems derived from Europe. Methods and results We identified 280 588 admissions with NSTEMI in the UK Myocardial Infarction National Audit Project (MINAP), 2010–2017, including White patients (n = 258 364) and Black, Asian, and Minority Ethnic (BAME) patients (n = 22 194). BAME patients were younger (66 years vs. 73 years, P Conclusion BAME patients with NSTEMI had higher cardiometabolic risk profiles and were more likely to undergo invasive angiography and revascularization, with similar clinical outcomes as those of their White counterparts. Among the quality indicators assessed, there is no evidence of care disparities among BAME patients presenting with NSTEMI.

Patients with acute coronary syndromes (ACS), particularly non-ST-segment elevation ACS, represent a spectrum of patients at variable risk of short- and long-term adverse clinical outcomes. Accurate prognostic assessment in this population requires the simultaneous consideration of multiple clinical and laboratory variables which may be under-recognized by the treating physicians, leading to an observed risk-treatment paradox in the use of invasive and pharmacological therapies. The routine application of established clinical risk scores, such as the Global Registry of Acute Coronary Events risk score, is recommended by major international clinical practice guidelines for structured risk stratification at the time of presentation, but uptake remains inconsistent. This article discusses the methodology of designing, deriving, and validating clinical risk scores, reviews the major validated risk scores for assessing prognosis in ACS, and examines their role in guiding clinical decision-making in ACS management, especially the timing of invasive coronary angiography. We also discuss emerging data on the impact of the routine use of such risk scores on patient management and clinical outcomes, as well as future directions for investigation in this field.

Aims We estimated the 2020 European Society of Cardiology-Acute Cardio Vascular Care (ESC-ACVC) quality indicators (QI) for the management of acute myocardial infarction, from three existing registries to determine the feasibility of assessment, room for improvement, association with outcomes, and suitability for centre benchmarking. Methods and results Data were extracted from three French nationwide registries, namely FAST-MI 2005, 2010, and 2015. Feasibility of assessment and room for improvement were estimated by the denominator (patients in whom QI could be measured) and numerator (patients who satisfied the QI, among those eligible). Associations between composite QIs (CQIs) and mortality were assessed by multivariate analysis. Centre benchmarking was based on the centres mean CQI, vs. the national mean. The 2020 QIs were measured in 12 660/13 130 patients from FAST-MI. Measurement feasibility ranged from 15% to 100% with greater potential for implementation with the 2020 QI set. The mean (±SD) value of the opportunity-based CQI was 0.72 ± 0.01 and attainment of the all-or-none CQI 8.5%. Both CQIs were associated with adjusted 1-year mortality. Centre categorization into low, intermediate, and high quality was feasible, and distinguished centres with differing mortality. Conclusion Most of the 2020 QI can be measured from existing registries in all domains but not in the patient’s satisfaction domain. This assessment shows potential for implementation. Both CQIs were inversely associated with one-year mortality and centre benchmarking was feasible.

Background Atrial fibrillation (AF) is common in older people and is associated with increased stroke risk that may be reduced by oral anticoagulation (OAC). Frailty also increases with increasing age, yet the extent of OAC prescription in older people according to extent of frailty in people with AF is insufficiently described. Methods An electronic health records study of 536,955 patients aged ≥65 years from ResearchOne in England (384 General Practices), over 15.4 months, last follow-up 11th April 2017. OAC prescription for AF with CHA2DS2-Vasc ≥2, adjusted (demographic and treatments) risk of all-cause mortality, and subsequent cerebrovascular disease, bleeding and falls were estimated by electronic frailty index (eFI) category of fit, mild, moderate and severe frailty. Results AF prevalence and mean CHA2DS2-Vasc for those with AF increased with increasing eFI category (fit 2.9%, 2.2; mild 11.2%, 3.2; moderate 22.2%, 4.0; and severe 31.5%, 5.0). For AF with CHA2DS2-Vasc ≥2, OAC prescription was higher for mild (53.2%), moderate (55.6%) and severe (53.4%) eFI categories than fit (41.7%). In those with AF and eligible for OAC, frailty was associated with increased risk of death (HR for severe frailty compared with fit 4.09, 95% confidence interval 3.43–4.89), gastrointestinal bleeding (2.17, 1.45–3.25), falls (8.03, 4.60–14.03) and, among women, stroke (3.63, 1.10–12.02). Conclusion Among older people in England, AF and stroke risk increased with increasing degree of frailty; however, OAC prescription approximated 50%. Given competing demands of mortality, morbidity and stroke prevention, greater attention to stratified stroke prevention is needed for this group of the population.

Aims To investigate trends in the prescription of oral anticoagulants (OACs) and antiplatelet agents for atrial fibrillation (AF). Methods and results Prescription data for 450 518 patients with AF from 3352 General Practices in England, was obtained from the GRASP-AF registry, 2009–2018. Annualized temporal trends for OAC and antiplatelet prescription were reported according to eligibility based on stroke risk (CHADS2 or CHA2DS2-VASc scores ≥1 or >2, respectively). From 2009 to 2018, the prevalence of AF increased from 1.6% [95% confidence interval (CI) 1.5–1.7%] to 2.4% (2.3–2.5%), and for those with AF the proportion prescribed OAC increased from 47.6% to 75.0% (P-trend < 0.001; relative risk 1.57, 95% CI 1.55–1.60) and for antiplatelet decreased from 37.4% to 9.2% (P-trend < 0.001). In early-years (2009–2013), eligible patients aged ≥80 years were less likely to be prescribed OAC than patients aged Conclusion Between 2009 and 2018, in England, the use of OAC for stroke prophylaxis in AF increased, with DOAC accounting for over half of OAC uptake in 2018. Despite a reduction in the OAC-prescription gap, a new paradox exists relating to DOAC prescription for the elderly and those at higher risk of stroke.

The availability of large datasets from multiple sources [e.g. registries, biobanks, electronic health records (EHRs), claims or billing databases, implantable devices, wearable sensors, and mobile apps], coupled with advances in computing and analytic technologies, have provided new opportunities for conducting innovative health research. Equally, improved digital access to health information has facilitated the conduct of efficient randomized controlled trials (RCTs) upon which clinical management decisions can be based, for instance, by permitting the identification of eligible patients for recruitment and/or linkage for follow-up via their EHRs. Given these advances in cardiovascular data science and the complexities they behold, it is important that health professionals have clarity on the appropriate use and interpretation of observational, so-called ‘real-world’, and randomized data in cardiovascular medicine. The Cardiovascular Roundtable of the European Society of Cardiology (ESC) held a workshop to explore the future of RCTs and the current and emerging opportunities for gathering and exploiting complex observational datasets in cardiovascular research. The aim of this article is to provide a perspective on the appropriate use of randomized and observational data and to outline the ESC plans for supporting the collection and availability of clinical data to monitor and improve the quality of care of patients with cardiovascular disease in Europe and provide an infrastructure for undertaking pragmatic RCTs. Moreover, the ESC continues to campaign for greater engagement amongst regulators, industry, patients, and health professionals in the development and application of a more efficient regulatory framework that is able to take maximal advantage of new opportunities for improving the design and efficiency of observational studies and RCT in patients with cardiovascular disease.

Background Statins reduce the risk of major adverse cardiovascular events (MACE), however, their clinical benefit for primary and secondary prevention among older adults with frailty is uncertain. This review investigates whether statins prescribed for primary and secondary prevention are associated with reduced MACE among adults aged ≥65 years with frailty. Methods Systematic review of studies published between 01.01.1952 and 01.01.2019 in MEDLINE, Embase, Scopus, Web of Science, Cochrane Library and the International Pharmaceutical Abstracts. Studies that investigated the effect of statins on MACE among adults ≥65 years with a validated frailty assessment were included. Data were extracted from the papers as per a pre-published protocol, PROSPERO: CRD42019127486. Risk of bias was assessed using the Cochrane Risk of Bias in non-randomised studies of interventions. Finding 18794 abstracts were identified for screening. From these, six cohort studies fulfilled the inclusion criteria. There were no randomised clinical trials. Of studies involving statins for primary and secondary prevention (n = 6), one found statins were associated with reduced mortality (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.37–0.93) and another found they were not (p = 0.73). One study of statins used for secondary prevention found they were associated with reduced mortality (HR 0.28, 95%CI 0.21–0.39). No studies investigated the effect of statins for primary prevention or the effect of statins on the frequency of MACE. Discussion This review summarizes the existing available evidence for decision making for statin prescribing for older adults with frailty. This study identified only observational evidence that, among older people with frailty, statins are associated with reduced mortality when prescribed for secondary prevention, and an absence of evidence evaluating statin therapy for primary prevention. The findings of this study highlight that randomised trial data are urgently needed to better inform the use of statins among older adults living with frailty.

Aims To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments. Methods and results National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 patients, Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)] and the UK [n = 247, 662 529 patients, Myocardial Ischaemia National Audit Project (MINAP)] between 2003 and 2013. There were lower rates of revascularization [STEMI (43.8% vs. 74.9%); NSTEMI (27.5% vs. 43.6%)] and pharmacotherapies at time of hospital discharge including [aspirin (82.9% vs. 90.2%) and (79.9% vs. 88.0%), β-blockers (73.4% vs. 86.4%) and (65.3% vs. 85.1%)] in the UK compared with Sweden, respectively. Standardized net probability of death (NPD) between admission and 1 month was higher in the UK for STEMI [8.0 (95% confidence interval 7.4–8.5) vs. 6.7 (6.5–6.9)] and NSTEMI [6.8 (6.4–7.2) vs. 4.9 (4.7–5.0)]. Between 6 months and 1 year and more than 1 year, NPD remained higher in the UK for NSTEMI [2.9 (2.5–3.3) vs. 2.3 (2.2–2.5)] and [21.4 (20.0–22.8) vs. 18.3 (17.6–19.0)], but was similar for STEMI [0.7 (0.4–1.0) vs. 0.9 (0.7–1.0)] and [8.4 (6.7–10.1) vs. 8.3 (7.5–9.1)]. Conclusion Short-term mortality following STEMI and NSTEMI was higher in the UK compared with Sweden. Mid- and longer-term mortality remained higher in the UK for NSTEMI but was similar for STEMI. Differences in mortality may be due to differential use of guideline-indicated treatments.

Background Over 800,000 women in the UK are living with coronary heart disease, which is the main cause of acute myocardial infarction (AMI). Marked improvements have been noted in clinical outcomes following AMI due to improved use of evidence-based treatments. However, sex differences in outcomes following AMI persist, with limited evidence in the literature concerning patient reported outcomes such as health related quality of life (HRQoL). Purpose To investigate sex differences in HRQoL following AMI. Methods Data on HRQoL among 9,566 survivors of AMI were collected from 77 National Health Service hospitals in England between 1 November 2011 and 24 June 2015. HRQoL at time of hospitalisation with an AMI as well as at 1, 6 and 12 months post discharge were collected using the self-reported EuroQol five dimension questionnaire which contains a descriptive system (EQ-5D ranging from −0.5 “worse than death” to 1 “full health”) and a visual analogue scale (EQ-VAS ranging from 0 “worst imaginable health state” to 100 “best imaginable health state”). Multilevel regression modelling coupled with inverse probability weighting propensity score analysis was used to investigate longitudinal trajectories of sex differences in perceived HRQoL following AMI. Results Overall, there were 2,397 (25%) women in the study. HRQoL improved over time, however, women had a lower baseline HRQoL compared with men (EQ-VAS mean (SD) 59.8 (20.4) vs. 64.5 (20.9), and EQ-5D median (IQR) 0.73 (0.52 to 0.88) vs. 0.81 (0.62 to 1.00). Sex differences in HRQoL over time persisted, with women having a reduced HRQoL (EQ-VAS coefficient: −4.41, 95% CI: −5.16 to −3.66 and EQ-5D coefficient: −0.07, −0.08 to −0.06) and across the individual EQ-5D dimensions women were more likely to report problems with anxiety (odds ratio 2.03, 95% CI: 1.80 to 2.29), mobility (1.82, 1.58 to 2.09), self-care (1.75, 1.47 to 2.08), usual activities (1.70, 1.52 to 1.89) and pain (1.59, 1.45 to 1.75). Conclusion Although quality of life improves for AMI survivors, women have a lower baseline and worse recovery compared with men. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation, Wellcome Trust, Sir Henry Wellcome Postdoctoral Fellowship

Background At least 10 million people in Europe have a diagnosis of atrial fibrillation (AF). People with AF commonly have concomitant frailty, rendering them vulnerable to various adverse outcomes. Whilst appropriate prescription of oral anticoagulation (OAC) is associated with reduced risk of stroke and mortality, there are fears of iatrogenic harm in older people with frailty. Purpose Previous studies give conflicting evidence of the association between frailty and OAC prescription and are based on small samples from select cohorts. Therefore, we provide data of the association between OAC prescription and frailty for a large representative cohort of patients with AF. Methods This cross-sectional study used EHR for 536,955 patients in England aged ≥65 years on 31/12/2015. Clinical Terms Version 3 (CTV-3) codes were used to identify AF and relevant past medical history (PMH, including: cancer, varices, intracranial or gastrointestinal haemorrhage). Frailty was determined according to the validated electronic frailty index (eFI, a cumulative deficit score of 36 possible deficits), and categorised into robust (0–0.12), mild (>0.12–0.24), moderate (>0.24–0.36) or severe (>0.36) frailty. Patients with a CHA2DS2-VASc score of ≥2 were considered eligible for OAC prescription. Prescription of OAC among those eligible (warfarin or direct oral anticoagulant [DOAC]) or not was established using prescribing data within the EHR. Poisson regression modelling was used to determine the odds of OAC prescription for each frailty category compared with non-frail (robust) individuals. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported with and without adjustment for sex, deprivation, PMH, concomitant prescription of medications that increase bleeding risk (including antiplatelets, steroids, non-steroidal anti-inflammatories). Results Of the cohort, 61,177 (11.4%) had AF. Of these, 58,204 (95.1%) were eligible for OAC, which was prescribed in 30,916 (53.1%) people. Individuals prescribed OAC were on average 5 months younger than those not prescribed OAC (80.1 vs 80.5 years, p OAC was prescribed in 2,028 of 4,863 (41.7%) patients in the robust category; 10,221 of 19,198 (53.2%) with mild; 11,167 of 20,099 (55.6%) with moderate; and 7,500 of 14,044 (53.4%) with severe frailty. In comparison to the robust category, frailty was associated with higher odds of OAC prescription: mild frailty OR 1.6 (95% CI 1.5 to 1.7); moderate 1.7 (1.6 to 1.9); severe 1.6 (1.5 to 1.7). Adjustment for confounding variables increased the magnitude of the association (Figure 1). Conclusion People with AF and advancing frailty were more likely to be prescribed an anticoagulant than those with AF who are robust. Specific safety and efficacy data for OAC are needed in people with AF and frailty to better inform clinical decision-making. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): CW was funded by the Hull-York Medical School. He is now an NIHR clinical lecturer.

Background Two thirds of patients with Acute Myocardial Infarction (AMI) arrive at hospital in the UK by ambulance, usually staffed by paramedics who routinely carry out 12 lead ECGs for patients with suspected heart attack. However, recent research found that prehospital ECGs were missing for 40% of these patients, with better survival prospects in those who had received one. Purpose We are investigating reasons for non-administration of 12 lead ECG for patients diagnosed with AMI, in order to develop an intervention to improve practice. Firstly we explored whether the proportion of patients with AMI that receive a prehospital ECG has changed over time. Methods Interrogation of national UK national heart attack register (MINAP) database, extraction of data related to patients brought by ambulance by year. Results The cohort of patients diagnosed with AMI and taken to hospital by ambulance ranged from 32410 in 2005 to 60265 in 2017; the proportion with a prehospital ECG increased steadily across this period, from 51% to 78%, an average increase of 1.9% per annum. Conclusions Evidence based guidelines supporting the use of 12 lead ECG by ambulance paramedics may have contributed to improvements in care. However, 1 in 5 patients brought to hospital by ambulance still does not receive an ECG prior to arrival, which we know compromises their survival prospects. In order to optimise care we need to establish whether non-administration is a question of misdiagnosis, patient refusal or lack of availability of trained crews/equipment. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Aims COVID-19 might have affected the care and outcomes of hospitalized acute myocardial infarction (AMI). We aimed to determine whether the COVID-19 pandemic changed patient response, hospital treatment, and mortality from AMI. Methods and results Admission was classified as non-ST-elevation myocardial infarction (NSTEMI) or STEMI at 99 hospitals in England through live feeding from the Myocardial Ischaemia National Audit Project between 1 January 2019 and 22 May 2020. Time series plots were estimated using a 7-day simple moving average, adjusted for seasonality. From 23 March 2020 (UK lockdown), median daily hospitalizations decreased more for NSTEMI [69 to 35; incidence risk ratios (IRR) 0.51, 95% confidence interval (CI) 0.47–0.54] than STEMI (35 to 25; IRR 0.74, 95% CI 0.69–0.80) to a nadir on 19 April 2020. During lockdown, patients were younger (mean age 68.7 vs. 66.9 years), less frequently diabetic (24.6% vs. 28.1%), or had cerebrovascular disease (7.0% vs. 8.6%). ST-elevation myocardial infarction more frequently received primary percutaneous coronary intervention (81.8% vs. 78.8%), thrombolysis was negligible (0.5% vs. 0.3%), median admission-to-coronary angiography duration for NSTEMI decreased (26.2 vs. 64.0 h), median duration of hospitalization decreased (4 to 2 days), secondary prevention pharmacotherapy prescription remained unchanged (each > 94.7%). Mortality at 30 days increased for NSTEMI [from 5.4% to 7.5%; odds ratio (OR) 1.41, 95% CI 1.08–1.80], but decreased for STEMI (from 10.2% to 7.7%; OR 0.73, 95% CI 0.54–0.97). Conclusion During COVID-19, there was a substantial decline in admissions with AMI. Those who presented to hospital were younger, less comorbid and, for NSTEMI, had higher 30-day mortality.

Aims The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources. Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases. To survey health professionals’ views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents. Methods and results 3101 responses were received from 141 countries across 6 continents. 88.3% responded that their country was in “total lockdown” and 7.1% in partial lockdown. 78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%. Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis. Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service. Conclusion The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring. This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic.

Aim: To study the association between time of hospitalization and in-hospital mortality for acute myocardial infarction (AMI). Methods and Results: Patients admitted with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) across 243 hospitals in England and Wales between 1st January 2004 and 31st March 2013 were included. The outcome measure was in-hospital mortality. Adjusted odds ratios for in-hospital mortality were estimated across six four-hourly time periods over the 24-hour clock using multilevel logistic regression, inverse-probability weighting propensity score and instrumental variable analysis. Among 615,035 patients (median age 70.0 years, IQR 59.0 - 80.0 years; 406,519 (66.0%) men), there were 52,777 (8.8%) in-hospital deaths. At night, patients with NSTEMI were more frequently co-morbid, and for STEMI had longer symptom-onset-to-reperfusion times. For STEMI, unadjusted in-hospital mortality was highest between 20:00 and 23:59 (four-hour period range 8.4% to 9.9%; OR compared with 00:00 to 03:59 reference 1.13, 95% CI 1.07 to 1.20), and for NSTEMI highest between 12:00 to 15:59 (8.0% to 8.8%; OR compared with 00:00 to 03:59 reference 1.07, 95% CI 1.03 to 1.12). However, these differences were only apparent in the earlier years of the study, and were attenuated by adjustment for demographics, co-morbidities and clinical presentation. Differences were not statistically significant after adjustment for acute clinical treatment provided. Conclusions: There is little evidence to support an association between time of hospitalization and in-hospital mortality for acute myocardial infarction; variation in in-hospital mortality may be explained by case mix and the use of treatments.

Aims Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction. Methods and results A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that β-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64–0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77–1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated. Conclusion Evidence from this study suggests that there is no association between β-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.

Background The prevalence of atrial fibrillation (AF) in older people is increasing, as is frailty. Frailty describes an increased vulnerability to adverse outcomes, whereby the balance of risk and benefit associated with an intervention may be more nuanced. However, there are limited data from a community setting on the prevalence of AF and frailty in older people. It is important to understand the burden of AF and frailty, and the associated impact on mortality and stroke disease in order to inform shared decision making with patients, and also inform guidelines for this increasing group of older people. Purpose To estimate the prevalence of AF and the burden of frailty in patients with AF, in a large primary care dataset. To report stroke and mortality by frailty group. Methods We used electronic health records of 537,051 patients in England aged 65 years or older on 31/12/2015, with follow-up for all-cause mortality and ischaemic or unclassified stroke to 11/04/2017. Patients with a history of AF were identified using Clinical Terms Version 3 (CTV-3) codes. Frailty was identified up to the point of study entry using the electronic frailty index (eFI, the proportion of deficits out of 36 possible deficits), and categorised into robust (0–0.12), mild (>0.12–0.24), moderate (>0.24–0.36) or severe (>0.36) frailty. Median CHA2DS2-VASc and ATRIA scores for patients with frailty were compared with the robust group using Mann-Whitney. The association between frailty status, all-cause mortality and stroke was calculated using Cox proportional hazards models, adjusted for age and sex. Results Of the cohort, 61,177 patients (11.4%) had AF. Of those with AF, 27,987 (45.8%) were female, and 54,734 (89.5%) had frailty. 6,443 (10.5%) were classified as robust; 20,352 (33.3%) mildly frail; 20,315 (33.2%) moderately frail; and 14,067 (23.0%) severely frail. The median number of eFI-defined deficits among patients with AF was 9 (interquartile range [IQR] 6–12). Median stroke and bleeding scores were higher in those with frailty compared with the robust group (CHA2DS2-VASc 4 [IQR 3–5] v 2 [2–3], p≤0.001; ATRIA 4 [2–6] v 1 [0–2], p≤0.001). During 73,338 patient-years of follow-up, there were 6,805 (11.1%) deaths and 945 (1.54%) strokes. Compared with the robust group, all-cause mortality and stroke were higher with increasing frailty. Mortality: mild frailty hazard ratio 1.53 (95% confidence interval 1.29–1.80); moderate frailty 2.50 (2.13–2.94); severe frailty 4.26 (3.63–5.01). Stroke: mild frailty 1.36 (0.99–1.85); moderate frailty 1.67 (1.23–2.28); severe 1.99 (1.45–2.73). Kaplan-Meier survival curves by frailty Conclusion The prevalence of AF among those aged over 65 years in primary care in England is high, the majority of whom are frail. Increasing severity of frailty was associated with higher mortality and stroke rates. The extent to which the judicious use of oral anticoagulation may improve clinical outcomes for patients with AF and frailty is currently unknown. Acknowledgement/Funding CPG: Bayer, BMS, AstraZeneca, Novartis Vifor Pharma, Menerini

Aims The Myocardial Ischaemia National Audit Project (MINAP) collects data from admissions in England, Wales, and Northern Ireland with Type 1 myocardial infarction (T1 MI). The project aims to improve clinical care through the audit process and to provide powerful high-resolution data for research. Methods and results MINAP collects data spanning 130 data fields covering the course of patient care, from the moment the patient calls for professional help through to hospital discharge and rehabilitation. Data are entered by clinicians and clerical staff within hospitals, and pseudonymized records are uploaded centrally to the National Institute for Cardiovascular Outcomes Research (NICOR), hosted by Barts Health NHS Trust, London, UK. Two hundred and six hospitals submit over 92 000 new cases to MINAP annually. Approximately 1.5 million patient records are currently held in the database. Patient demographics, medical history, clinical assessment, investigations, treatments, drug therapy prior to admission, during hospital stay, and at discharge are collected. Data completeness of three key data fields (age, admission blood pressure, and heart rate) is over 91%. Vital status following hospital discharge is obtained via linkage to data from the United Kingdom Office for National Statistics. An annual report is compiled using these data, with individual hospital summary data included. Datasets are available to researchers by application to NICOR. Conclusion MINAP is the largest single healthcare system heart attack registry, and includes data from hospitalizations with T1 MI in England, Wales, and Northern Ireland. It includes high-resolution data across the patient pathway and is a powerful tool for quality improvement and research.

Aims: Early and accurate diagnosis of acute myocardial infarction is central to successful treatment and improved outcomes. We aimed to investigate the impact of the initial hospital diagnosis on mortality for patients with acute myocardial infarction. Methods and results: Cohort study using data from the Myocardial Ischaemia National Audit Project of patients discharged with a final diagnosis of ST-elevation myocardial infarction (STEMI, n=221,635) and non-STEMI (NSTEMI, n=342,777) between 1 April 2004 and 31 March 2013 in all acute hospitals ( n = 243) in England and Wales. Overall, 168,534 (29.9%) patients had an initial diagnosis which was not the same as their final diagnosis. After multivariable adjustment, for STEMI a change from an initial diagnosis of NSTEMI (time ratio 0.97, 95% confidence interval 0.92–1.01) and chest pain of uncertain cause (0.98, 0.89–1.07) was not associated with a significant reduction in time to death, whereas for other initial diagnoses the time to death was significantly reduced by 21% (0.78, 0.74–0.83). For NSTEMI, after multivariable adjustment, a change from an initial diagnosis of STEMI was associated with a reduction in time to death of 10% (time ratio 0.90, 95% confidence interval 0.83–0.97), but not for chest pain of uncertain cause (0.99, 0.96–1.02). Patients with NSTEMI who had other initial diagnoses had a significant 14% reduction in their time to death (time ratio 0.86, 95% confidence interval 0.84–0.88). STEMI and NSTEMI with other initial diagnoses had low rates of pre-hospital electrocardiograph (24.3% and 21.5%), aspirin on hospitalisation (61.6% and 48.5%), care by a cardiologist (60.0% and 51.5%), invasive coronary procedures (38.8 % and 29.2%), cardiac rehabilitation (68.9% and 62.6%) and guideline indicated medications at time of discharge from hospital. Had the 3.3% of patients with STEMI and 17.9% of NSTEMI who were admitted with other initial diagnoses received an initial diagnosis of STEMI and NSTEMI, then 33 and 218 deaths per year might have been prevented, respectively. Conclusion: Nearly one in three patients with acute myocardial infarction had other diagnoses at first medical contact, who less frequently received guideline indicated care and had significantly higher mortality rates. There is substantial potential, greater for NSTEMI than STEMI, to improve outcomes through earlier and more accurate diagnosis of acute myocardial infarction.

Adherence to guideline-indicated care for the treatment of non-ST-elevation myocardial infarction (NSTEMI) is associated with improved outcomes. We investigated the extent and consequences of non-adherence to guideline-indicated care across a national health system.A cohort study ( ClinicalTrials.gov identifier: NCT02436187) was conducted using data from the Myocardial Ischaemia National Audit Project ( n = 389,057 NSTEMI, n = 247 hospitals, England and Wales, 2003-2013). Accelerated failure time models were used to quantify the impact of non-adherence on survival according to dates of guideline publication.Over a period of 1,079,044 person-years (median 2.2 years of follow-up), 113,586 (29.2%) NSTEMI patients died. Of those eligible to receive care, 337,881 (86.9%) did not receive one or more guideline-indicated intervention; the most frequently missed were dietary advice ( n = 254,869, 68.1%), smoking cessation advice ( n = 245,357, 87.9%), P2Y12 inhibitors ( n = 192,906, 66.3%) and coronary angiography ( n = 161,853, 43.4%). Missed interventions with the strongest impact on reduced survival were coronary angiography (time ratio: 0.18, 95% confidence interval (CI): 0.17-0.18), cardiac rehabilitation (time ratio: 0.49, 95% CI: 0.48-0.50), smoking cessation advice (time ratio: 0.53, 95% CI: 0.51-0.57) and statins (time ratio: 0.56, 95% CI: 0.55-0.58). If all eligible patients in the study had received optimal care at the time of guideline publication, then 32,765 (28.9%) deaths (95% CI: 30,531-33,509) may have been prevented.The majority of patients hospitalised with NSTEMI missed at least one guideline-indicated intervention for which they were eligible. This was significantly associated with excess mortality. Greater attention to the provision of guideline-indicated care for the management of NSTEMI will reduce premature cardiovascular deaths.

Survival after non-ST-elevation myocardial infarction (NSTEMI) is high and non-cardiovascular death has become more frequent. Observational studies typically quantify quality of care and clinical outcomes using all-cause mortality, which nowadays may not reflect the impact of index NSTEMI. We review and investigate relative survival for quantifying longer term outcomes after NSTEMI. National cohort study of hospitalized NSTEMI (Myocardial Ischaemia National Audit Project; patients: n = 346 546, hospitals: n = 243, countries: England and Wales). Mortality rates derived from two relative survival techniques were compared with all-cause mortality, and the impact of relative survival adjusted patient characteristics compared with those from Cox proportional estimates. Cox proportional hazards models provide lower survival estimates because they include deaths from all causes, overestimate the impact of increasing age on survival, and underestimate temporal improvements in care. The Royston–Parmar model allows more accurate estimation of relative survival because it is flexible to the high early hazard of death after hospitalized NSTEMI. All-cause mortality gives an overall assessment of survival for a cohort of patients. Relative survival provides a more accurate and informed estimation of the impact of an index cardiovascular event and, if necessary, patient characteristics on survival.

This editorial refers to ‘Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry’[†][1], by K.M. Egger et al ., on page 2417. Cardiac troponins play a central role in the diagnosis of acute myocardial infarction (AMI) and the management of non-ST-segment elevation acute coronary syndromes (NSTEACS). The third universal definition bases the diagnosis of AMI on the ‘detection of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99th percentile upper reference limit’.1 The European Society of Cardiology (ESC) guidelines for the management of NSTEACS recommend an urgent invasive strategy, i.e. within 24 h, in patients with high-risk criteria, including those with a rise or fall in cardiac troponin compatible with MI.2 The early and accurate diagnosis of AMI is a key function of emergency departments. Delayed diagnosis may result in substandard initiation of AMI treatments, inadequate rule out of alternative diagnoses, and the failure to discharge very low risk patients—each being associated with the potential for increased costs and adverse clinical outcomes. Moreover, ‘negative’ cardiac troponin values may lead to patients with ACS who have small, but measureable, cardiac damage being inappropriately discharged from hospital. Such imperfections in ACS diagnostics triggered a race to develop higher sensitivity cardiac … [1]: #fn-2

Guidelines recommend exercise-based cardiac rehabilitation (EBCR) for patients with heart failure (HF). However, established research has not investigated the longer-term outcomes including mortality and hospitalisation in light of the contemporary management of HF.This was a systematic review including a meta-analysis of EBCR on all-cause mortality, hospital admission, and standardised exercise capacity using four separate exercise tests in patients with heart failure over a minimum follow-up of six months from January 1999-January 2013. Electronic searches were performed in the databases: Medline, CENTRAL, EMBASE, CINAHL, and PsycINFO constrained to randomised controlled trials (RCTs).A total of 46 separate RCTs qualified for the meta-analysis, which employed conventional methods for binary and continuous data. The relative risk (RR) ratio for hospital admission (12 studies) was significantly reduced (RR ratio 0.65; 95% confidence interval (CI) 0.50-0.84; p = 0.001), but mortality (21 studies) was not (RR ratio 0.88; 95% CI 0.77-1.02; p = 0.08). The standardised exercise capacity (26 studies) showed a standardised mean difference (SMD) in favour of the exercise group as compared with the controls (SMD 0.98, 95% CI 0.59-1.37; p 0.001). Women and elderly people were less frequently enrolled in the RCTs independent of the outcomes. Heterogeneity was moderate to high in the analysis of hospital admission and the standardised exercise capacity demonstrated through skewedness in their funnel plots.EBCR in patients with HF is associated with significant improvements in exercise capacity and hospital admission over a minimum of six months follow-up, but not in all-cause mortality.

This editorial refers to “Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry”, by E. Cenko et al ., on page 45. Reperfusion therapy, either by intravenous fibrinolysis or percutaneous coronary intervention (PCI), is the cornerstone of the management of ST-elevation myocardial infarction (STEMI).1 Randomized data have demonstrated its effectiveness in reducing mortality and morbidity, and the benefit is all the greater when it is performed early.2,3 As such, coronary reperfusion for STEMI performed within a short time frame is recommended and its timely implementation used as an indicator of quality of care.4 The estimated times to reperfusion also contribute largely to the choice of reperfusion strategy, with primary PCI being the technique of choice except if it is estimated that it cannot be performed within 120 min.1 Despite this, many patients fail to receive guideline-indicated therapies for STEMI and the proportion who do varies geographically.5 Addressing the variation in STEMI care will help reduce the substantial difference in mortality rates from cardiovascular disease between European countries.6 The choice of reperfusion strategy and the ability to … [↵][1]*Corresponding author. Tel: +44 01133438916, Email: c.p.gale{at}leeds.ac.uk [1]: #xref-corresp-1-1

The article by Yan et al. 1 measured the discriminatory performances of the TIMI, PURSUIT, and GRACE risk scores (RS) and suggested that they offered better prediction of in-hospital and 1-year mortality than that of global risk assessment by physicians.1 Moreover, the study revealed an inverse relationship between estimated risk and early invasive management when patients were stratified by RS, an important finding recently highlighted by Fox et al. 2 In the study by Yan et al. ,1 revascularization was more frequently based on physicians' global assessment, signifying that RS are not being used …

Purpose: High on-treatment P2Y12 reactivity (PRU) is associated with thrombotic events following PCI for ACS. Low PRU is associated with increased bleeding rates. There may be an optimal PRU range within which adverse events are minimised. Methods: Patients who presented with ACS from a prospective PCI registry were studied for the presence of an optimal PRU (VerifyNow) range relative to an on-treatment combined adverse event (CAE) of death, clinical MI, stroke and BARC 2 to 5 bleeding. Results: There were 864 patients (25.0% female, mean (SD) age 63.4 (17) years, clopidogrel 94.5%, prasugrel 5.5%), followed over a median (IQR) of 3.5 (2.9) years. The optimal range proposed by the ARMYDA-PROVE investigators (PRU 178 to 239) was the most useful for identifying patients at low risk of CAEs. Applying this range, 185 (21.4%) patients had an optimal PRU, 465 (53.8%) were hypo- and 214 (24.8%) hyper-responders. Most MIs (29 of 30) occurred within the first year; rates were higher in hypo-responders (4.5% versus 2.0%, p = 0.041). In contrast there were few bleeding events by 12 months with no difference between groups, but long-term bleeding rate was higher in hyper-responders (8.4% versus 4.6%, p=0.035). In hyper-, optimal and hypo-responders, CAE rate at 12 months was 7.9%, 2.2% and 8.0%, p=0.020; and at long-term follow-up 12.6%, 2.7% and 10.1%, p=0.002 (see figure). Optimal PRU was significantly negatively associated with CAEs at 1 year (adjusted hazard ratio (aHR) 0.18, 95% CI 0.04 to 0.74, p=0.017) and at long-term follow-up (aHR 0.21, 95% CI 0.06 to 0.66, p=0.008). Conclusions: Following PCI for ACS, optimal PRU is associated with a low rate of adverse clinical events. However, only about one fifth of patients on clopidogrel naturally fall into this category.

Purpose: Prompt reperfusion optimizes outcome of ST-elevation myocardial infarction (STEMI). Although programmes for delivering timely primary percutaneous coronary intervention (PPCI) in experienced centres have been implemented large inequality in the use of PPCI for STEMI across Europe is evident. We performed a comparative study looking to quantify variation in access to PPCI and factors associated with these observed differences at a national as well at a regional level. Knowledge on such factors hampering patients having access to PPCI, would be the first step in reducing inequality in access to life-saving treatment in Europe. Methods: An ecological study based on aggregated data from available national and international registries in Austria, Belgium, England, Germany, Italy, Portugal, Scotland, Sweden, Northern Ireland and Wales. Main outcome was number of PPCI per 1 million inhabitants, collected for the years 2003-2008. The individual country's yearly regional increase in implementation of PPCI was investigated by use of linear regression. We applied mixed effects regression models to study the relation between usage of PPCI and a set of health care-associated, economic and demographic regional-level parameters. Results: We detected a large variation in the absolute numbers of PPCI per million inhabitants between the different regions. Regional-level rates varied from 0.74 (95% CI 0.42, 1.30) to 1.90 (95% CI 1.01, 3.55) per million inhabitants per year. Regional inequalities were largest in Italy, Spain and Sweden. Significant positive associations with PPCI utilisation were number of physicians per 100,000 inhabitants; number of nurses and midwifes per 100,000 inhabitants; and the proportion of the regions population aged 50 to 70 years. Conclusions: Between 2003 and 2008, PPCI utilisation increased significantly in all European countries, but there was great variation within country regions. Regional variation in PPCI rates was associated with both demographic and supply factors. Implementation strategies focusing on these factors would most likely hasten PPCI uptake in the communities, and thereby be the first step in securing equal access to evidence-based treatment regardless of residency.