Definition of ACS
Acute coronary syndromes (ACS) include unstable angina and acute myocardial infarction (AMI). AMI is classified according to those patients with electrocardiographic ST-segment elevation, ST-elevation myocardial infarction (STEMI) and those without electrocardiographic ST-segment elevation, non-ST-elevation myocardial infarction (NSTEMI).1 The requirement for a diagnosis of AMI in the universal definition is the detection of troponin release from injured cardiac myocytes with at least one value >99th centile of the upper reference limit.1 Diagnosis is confirmed only if this is associated with at least one of: symptoms of ischaemia, new ST-segment or T-wave changes or new left bundle branch block on electrocardiography (ECG), development of pathological Q-waves on ECG, imaging evidence of new loss of viable myocardium or new regional wall motion abnormality or the identification of an intracoronary thrombus by angiography or at postmortem examination.
Rates of AMI in the UK
In 2014/15, there were 83,842 admissions to National Health Service (NHS) hospitals in England and Wales, Northern Ireland and Isle of Man with AMI as recorded in the UK national registry,2 Myocardial Ischaemia National Audit Project (MINAP). Of these, STEMI and NSTEMI comprised 40.5% and 59.5%, respectively. The ratio of STEMI to NSTEMI hospitalisations as recorded in MINAP has not changed over the last five years, from 1:1.50 in 2009/10 to 1:1.47 in 2014/15 (figure 1).2,3 Data from the British Heart Foundation (BHF) report that about 530 people are hospitalised each day in the UK with AMI.4 Primary care data from 2013 in the UK, suggests that the prevalence of AMI in men is about three-fold greater than for women, and that over 915,000 people in the UK have had an AMI.5
While recent data from MINAP suggest rates of hospitalised AMI have remained constant at about 80,000 cases annually, evidence from temporal analyses of national data extending earlier in time suggests that the incidence of ACS is in decline. A UK study using Hospital Episode Statistics (HES) reported a decrease, between 2002 and 2010, in the age standardised AMI event rate per 100,000 population in men of 33% from 230 (95% confidence interval [CI] 228 to 232) to 154 (95% CI 153 to 155) and in women of 31% from 95.4 (95% CI 94.5 to 96.3) to 66.0 (95% CI 65.3 to 66.7).6 Community-based data from the USA also report a decline in the incidence of AMI between 1998 and 2008, which was driven by a decrease in the incidence of STEMI.7 Notably, the rate of NSTEMI increased, and suggests a changing pattern of presentation with ACS.
Survival and re-event rates
Data from MINAP suggest that between 2003 and 2010 the risk of in-hospital mortality from AMI halved.8 Case fatality rates at 30 days following hospitalisation with AMI, as determined by HES, show similar trends between 2002 and 2010 with a decline from 18.5% to 12.2% in men and from 20.0% to 12.5% in women.6 However, the rates of decline are unequal across age bands, determined by comorbidity, AMI type and associated with the receipt of guideline-indicated treatments (figure 2).9-11 An analysis of 389,057 cases of hospitalised NSTEMI in the UK reported that between 2003 and 2013, unadjusted all-cause mortality at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio [HR] 0.968, 95% CI 0.966 to 0.971; difference in absolute mortality rate per 100 patients –1.81, 95% CI –1.95 to –1.67). For coronary heart disease in general, in the UK, death rates have fallen by 73% between 1975 and 2013 (age standardised death rate per 100,000: 469 in 1975 vs. 126 in 2013).12
Despite temporal improvements in outcomes from ACS, mortality rates for this population remain high. According to the BHF Heart Statistics, in 2014, coronary heart disease accounted for 69,163 deaths in the UK, of which the highest numbers for men were for the ages between 75 and 84 years (13,421) and for women for the ages greater than 85 years (13,985).12 In 2012, coronary heart disease was the most common single cause of premature death (death before the age of 75 years) in the UK in men, responsible for about 15% of premature male deaths and 8% of premature female deaths.5
Although all-cause mortality is higher among STEMI than NSTEMI, this is only evident early after the hospital presentation; among those surviving to hospital discharge, case fatality from NSTEMI is higher than STEMI.13 Registry-based studies report a cumulative risk of death following AMI (12.1% at six months vs. 39.2% at four years),14 and there is evidence from randomised and observational data for higher rates of death for NSTEMI compared with STEMI in the longer-term.13,15,16
Nowadays, following percutaneous coronary intervention (PCI), non-cardiovascular death is more frequent than cardiovascular death.17 This epidemiological shift is emphasised by the burden, among survivors of AMI, of re-infarction, stroke and death, and has greater impact on future healthcare utilisation and lifetime costs when the index AMI occurs at a younger age and/or the patient is higher risk.18 That is, among one-year survivors of AMI aged over 65 years, the crude cumulative rate of death, re-infarction and stroke is about 30%.19
Rates of angiography/primary PCI versus medical management
An invasive coronary strategy for the management of AMI is guideline recommended and associated with improved clinical outcomes. For STEMI, primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy, provided it can be performed within the guideline-mandated times, irrespective of whether a patient presents to a PPCI-capable hospital.20 For NSTEMI, compared with a selective invasive strategy, a routine invasive strategy has been shown to improve clinical outcomes and reduce recurrent ACS episodes, subsequent rehospitalisation and revascularisation.21
Following an eight-year implementation, the diffusion of PPCI services across the NHS of England has reached a plateau of about 85% of cases of STEMI.22 Analysis of MINAP data suggest a yearly increase in the use of PPCI between 2003 and 2013 of 30% (incidence rate ratio 1.30, 95% CI 1.23 to 1.36) increase in PPCI utilisation (figure 3). However, in this study of 92,350 STEMI hospitalisations, older and sicker patients were less likely to receive PPCI and there was between hospital variation in PPCI rates not attributable to staffing levels. This suggests that PPCI has reached near saturation and only marginal gains in rates of PPCI are likely from hospital reconfiguration. While greater institutional operationalisation of the service through additional infrastructure development and the non-section of cases may improve PPCI utilisation, MINAP data also suggest many patients with STEMI present late to hospital and, therefore, a greater awareness among the public to increase recognition of symptoms and seek urgent medical attention is required.3 Moreover, national data from the British Cardiovascular Intervention Society (BCIS) national registry of PCI found that the weight of evidence against a centre-volume relationship between PPCI and 30-day mortality was equivalent to the weight of evidence for it.23
For NSTEMI, there is evidence that an invasive coronary strategy (coronary angiography, PCI and coronary artery bypass graft [CABG]) significantly explained the decline in rates of death in the UK. A UK study of 389,057 patients hospitalised with NSTEMI between 2003 and 2013, who demonstrated an increase in comorbidities and a decrease in predicted atherothrombotic risk, found that only an invasive coronary strategy was significantly associated with the temporal decline in all-cause mortality (figure 4).24 Other UK studies using MINAP data have revealed geographic variation in the provision of NSTEMI care, associated with potentially avoidable deaths.25,26
Risks of re-infarction – who is ‘very high-risk’?
National and international guidelines recommend that as soon as a diagnosis of unstable angina or NSTEMI is made, patients are formally assessed for their risk of future adverse cardiovascular events using an established risk scoring system that predicts six-month mortality.21,27-29 The Global Registry of Acute Coronary Events (GRACE) risk score was developed in the GRACE registry programme to assess in-hospital and six-month outcomes of death or non-fatal myocardial infarction.13,30 For these outcomes it was derived and validated in over 42,000 patients with external validation in further separate cohorts. For clinical use, simplified models were derived based upon eight variables to predict the risk of death, or death and non-fatal myocardial infarction (i.e. age, heart rate, systolic blood pressure, Killip class, creatinine concentration, elevated biomarkers of necrosis, cardiac arrest on admission and ST-deviation). These factors conveyed more than 90% of the total risk (c-statistic 0.81 for predicting death and 0.73 for predicting death or non-fatal MI from admission to six months after discharge). The GRACE risk score version 2 has better discrimination, offers an estimate of absolute risk, is suitable for use in hand-held electronic devices/smart phones, and its applicability in the acute setting is broadened by the ability to use substitutions for creatinine and Killip class.31 Whether the use of the GRACE risk score is associated with improvements in the use of guideline-indicated treatments and reduced major adverse cardiovascular events for patients hospitalised with NSTEMI and unstable angina is being investigated in an international randomised controlled trial in the UK (United Kingdom GRACE Interventions Study, UKGRIS) and Australia (Australian GRACE Interventions Study, AGRIS).32
For NSTEMI and unstable angina, high risk is defined according to the 2015 European Society of Cardiology (ESC) guidelines for the management of ACS in patients presenting without persistent ST-segment elevation, and includes patients with a GRACE risk score greater than 140, or a rise and fall in cardiac troponin compatible with myocardial infarction, or dynamic ST- or T-wave changes.21 Patients defined as high risk include those with haemodynamic instability or cardiogenic shock, recurrent or ongoing chest pain refractory to medical treatment, life-threatening arrhythmias or cardiac arrest, mechanical complications of myocardial infarction, acute heart failure, or recurrent dynamic ST–T-wave changes, particularly with intermittent ST-elevation.
Policies for prevention and their implementation
Increasing and maintaining public and physician awareness of ACS symptoms and treatments is a key to improving care and outcome in this population. Data from the UK suggest that nearly one in three patients with AMI had other diagnoses at first medical contact, who less frequently received guideline-indicated care and had significantly higher mortality rates.33 Other studies have found that the history of chest pain is of limited value in cases of suspected ACS.34,35 While the advent of higher sensitivity troponin assays will ensure that greater numbers of patients with ACS are hospitalised for guideline-indicated care, and without ACS are discharged from hospital, emphasis must be placed on lowering the index of suspicion for ACS in circumstances when its clinical presentation may not be typical.
Clearly, there are local level opportunities to ensure that all patients who have a diagnosis of ACS follow the treatment algorithms recommended by international guidelines. Notwithstanding this, there are patient groups with high rates of subsequent cardiovascular events, including women, the comorbid and those with diabetes, where additional and/or novel health technology innovations are required. In the future, the frail elderly will form a larger proportion of the ACS case presentation, who’s outcomes can be predicted using electronic health records data,36 and who will require care optimisation (that may include deselecting non-appropriate therapies) in an area where there is clinical uncertainty as to the benefits of applying or withdrawing medical interventions (figure 5).37,38
Evaluating and reporting care and outcomes is integral to quality improvement in modern healthcare. Recently, the European Society of Cardiology Acute Cardiovascular Care Association (ESC ACCA) developed a set of AMI quality indicators.39 These measurable indicators are derived from Class 1 Level A treatment recommendations, but also incorporate measures whose implementation is deemed to be important, such as centre facilities and patient satisfaction. They encompass the journey of care for patients with STEMI and NSTEMI and may be used to benchmark the conformity of actual practice with ESC guidelines for the management of AMI. The indicators have been applied to the UK (using MINAP data)40 and separately in France (using the French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction, FAST-MI),41 to show their significant negative association with mortality suggesting, therefore, that greater attainment of the ESC ACCA quality indicators for AMI will reduce deaths from AMI.
While huge advances have been made in treatments and outcomes for ACS, such that for those who are optimally managed all-cause mortality rates are low, the increasing age of the UK populace, their associated comorbidities and their enhanced cardiovascular survivorship is creating a population of ACS survivors with recurrent cardiovascular events (figure 6). This, combined with relatively limited advances in science that aim to address long-term cardiovascular outcomes, the introduction of higher sensitivity troponin assays that will potentially increase case detection of AMI, and the non-receipt of optimal ACS care, highlights the scope of the problem.
Addressing the unmet needs of patients with ACS through the application of evidence-based treatments, and the knowledge gap in healthy longevity through the development and use of technologies, pharmacotherapies and available national electronic records of patient data is the necessary next step in cardiovascular medicine for this vulnerable population.
Conflict of interest
CG has received consultancy fees from AstraZeneca, Novartis and Vifor Pharma, and speaker fees from AstraZeneca.
- Despite a decline in the incidence of acute myocardial infarction (AMI), in the UK there are over 80,000 hospitalisations each year for AMI
- There has been a decrease in the rates of early death associated with AMI but the risk of future fatal and non-fatal cardiovascular events following AMI is high
- Across the UK rates of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) are high and rates of PCI for non-ST-elevation myocardial infarction (NSTEMI) have increased
- The advent of higher-sensitivity troponins will enable improved diagnosis of patients with suspected acute coronary syndrome (ACS)
- Greater awareness about the management of ACS according to risk stratification of predicted future cardiovascular events may improve clinical outcomes for ACS
- Women, those with comorbidities, and the frail elderly, are at higher risk of adverse cardiovascular outcomes and require careful optimisation of treatment
- In future, the frail elderly and the multi-morbid will form a greater proportion of the ACS population, where there are many clinical uncertainties as regard to their ACS care
- Quality indicators for AMI have recently been developed. These can be applied to patients with ACS in the UK for the evaluation of care, and their attainment is negatively associated with mortality
- Scientific advances are required to enable a greater understanding of the survivorship trajectories of patients with ACS. Novel healthcare interventions may maintain healthy longevity
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