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Review
Coronary revascularisation in older patients with non-ST elevation acute coronary syndromes
  1. Hannah Sinclair1,2,
  2. Vijay Kunadian1,2
  1. 1Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
  2. 2Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  1. Correspondence to Dr Vijay Kunadian, Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, 3rd Floor William Leech Building, Newcastle upon Tyne NE2 4HH, UK; vijay.kunadian{at}newcastle.ac.uk

Abstract

With an ageing population, older patients with non-ST elevation acute coronary syndrome are at higher risk of adverse outcomes but are far less likely to receive invasive revascularisation, contemporary antiplatelet therapy or drug-eluting stents than their younger counterparts. Accurate risk stratification in the older age groups may aid individualised decision-making with respect to identifying which patients will benefit most from invasive revascularisation, but more research is needed in this field. Based on current knowledge in this field, it would be appropriate following risk stratification to offer optimal medical therapy plus invasive care to older patients at high risk of future cardiovascular events but at low risk of complications and to offer optimal medical therapy alone to those who are deemed low risk of future events with high risk of developing procedural complications and severely frail patients.

https://doi.org/10.1136/heartjnl-2015-307859

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    Introduction

    In 2013–2014, almost half of all myocardial infarctions (MIs) in the UK occurred among patients aged over 70 years.1 Older patients presenting with acute coronary syndrome (ACS) are at higher risk of poor outcomes even after adjustment for confounding factors, such as comorbidities.2 However, the rate of invasive angiography in patients with non-ST elevation ACS (NSTEACS) declines with age.3 This has led to an apparent treatment paradox, whereby the older patients with highest risk are the least likely to undergo invasive management despite having the most potential to gain from it.4 Despite the increasing size and importance of this high-risk population, there is major under-representation of older patients in cardiovascular research and a paucity of data regarding the invasive management of older patients with ACS. A systematic review of randomised controlled trials (RCTs) in ACS demonstrated that over a half of all RCTs between 1996 and 2000 did not enrol any patients over the age of 75 years, and a third actively excluded them.5

    This review aims to summarise the current evidence for the clinical efficacy and safety of invasive coronary revascularisation in older patients with NSTEACS and to provide directions for future research in this field.

    Epidemiology of acute coronary syndrome in older patients

    In the Global Registry of Acute Coronary Events (GRACE), the median age of patients was 65 years, and 24% were over the age of 75 years.6 However, nearly a half of patients with NSTEACS were over the age of 70 years, reflecting the later age of presentation of NSTEACS compared with ST elevation MI (STEMI). The proportion of women presenting with NSTEACS also increases with age (23% of those ≤64 years vs 32% of those aged 65–74 years vs 46% of those ≥75 years, p<0.001).7 The proportion of patients with ACS with previous angina (42% of those ≤64 years vs 62% of those aged 65–74 years vs 66% of those ≥75 years, p<0.001), MI (25% vs 37% vs 42%, p<0.001), heart failure (5% vs 13% vs 18%, p<0.001) and cerebrovascular disease (4% vs 10% vs 12%, p<0.001) also increases with age.7 The presence of such comorbidities can influence the diagnosis, treatment and prognosis of ACS and as such requires accurate documenting to allow correction for confounding factors.

    Age predicts adverse outcomes following acute coronary syndrome

    Older patients presenting with ACS are at high risk of poor short-term and long-term outcomes. Each 10-year increase in age confers a 70%–75% relative increase in in-hospital mortality in patients presenting with ACS (figure 1, table 1).2 ,8 In the GRACE registry, when comparing the youngest (<45 years) with the oldest (≥85 years) age groups, cardiogenic shock was nearly six times more common (1.6% vs 9.8%, p<0.0001), and the rate of major bleeding was nearly tripled (2.3% vs 6.6%, p<0.0001).8 Predictors of periprocedural mortality following percutaneous coronary intervention (PCI) in patients ≥75 years include presentation with haemodynamic instability (OR 10.5, 95% CI 7.24 to 15.3), chronic renal failure (OR 2.02, 95% CI 1.18 to 3.47), prior stroke (OR 1.78, 95% CI 1.09 to 2.88) and left main stem (LMS) disease (OR 1.76, 95% CI 1.08 to 2.87). Analysis of the PCI Registry of the Euro Heart Survey Programme demonstrated that patients >75 years were more likely to suffer a non-fatal stroke, major bleeding or renal failure requiring dialysis following PCI for ACS.9 This increased risk persists after hospital discharge. In a prospective cohort study that enrolled 7217 patients undergoing PCI in Rotterdam, mortality was higher in octogenarians at 30 days, 1 year and 4 years even after adjusting for confounding factors. There was no difference in MI following PCI in younger patients and octogenarians, but a lower rate of target vessel revascularisation in the octogenarian cohort.10

    View this table:
    Table 1

    Representation of older patients in registries of NSTEACS

    Figure 1
    Figure 1

    In-hospital mortality by age in acute coronary syndrome (ACS) registries.

    Risk assessment in older patients with ACS

    There are multiple risk prediction models for patients presenting with ACS that can be used to aid decision-making around invasive revascularisation. However, older patients are under-represented in the studies that validated these models. In addition, as age often accounts for a large proportion of the risk in the prediction models, it has been suggested that they are not as discriminating in identifying high-risk patients within older age categories. However, Vassalli et al calculated the GRACE, logistic EuroSCORE, Acute Myocardial Infarction Swiss (AMIS) registry and Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores in a series of 114 patients over 75 years with ACS.11 All four scores were associated with 30-day mortality: area under the receiver operating characteristic curve was 0.81 for EuroSCORE, 0.82 for AMIS, 0.83 for GRACE and 0.84 for SYNTAX. Combining all four scores resulted in an even higher predictive accuracy (area under the curve=0.88).11 Recently, Angeli et al12 showed that the risk for 1-year mortality in patients ≥75 years of age with NSTEACS is substantial and can be predicted through a score which included five statistically significant covariates: previous vascular event, haemoglobin level, estimated glomerular filtration rate, ischaemic electrocardiographic changes and elevated troponin level that can be easily derived at the bedside at hospital presentation.

    The association of frailty and adverse outcome in older patients with ACS

    Frailty is an important discriminating feature in older patients that has not so far been addressed by conventional ACS risk scores. Frailty is a vulnerability to physiological stressors due to a decline in reserve and resilience with age. Frailty can be assessed by Fried Frailty Index, derived from Cardiovascular Health Study13 and Rockwood Frailty Index, derived from Canadian Study of Health and Aging.14 The Fried Frailty Index is based on assessing five criteria, comprising subjective answers provided by the patient (regarding weight loss, physical energy, physical activity) and objective assessment (hand grip strength). A score of 0 is categorised as robust, 1 or 2 as intermediate or pre-frail and 3 or more as frail (table 2). The Rockwood Frailty Index is based on assessment by the researcher into categories 1–7, from very fit to severely frail, depending on functional status and independence/dependence on others for activities of daily living (table 3).

    View this table:
    Table 2

    Fried frailty index derived from cardiovascular health study

    View this table:
    Table 3

    Rockwood frailty index

    In a Swedish study of 307 patients with NSTEACS aged over 75 years, 49% were considered frail on the Rockwood Frailty Scale (categories 5–7).15 ,16 At 1 year, presence of frailty was associated with mortality (49% vs 13%, p<0.0001) and the composite outcome of death from any cause, reinfarction, revascularisation, hospitalisation for any cause, major bleeding, stroke/transient ischaemic attack (TIA) or need for dialysis (82% vs 69%, p=0.011)15 (figure 2). In another study (mean age 62±12 years consisting of patients with stable angina and ACS), frailty was associated with increased 30-day (HR 4.8, 95% CI 1.4 to 16.3, p=0.013) and 1-year mortality (HR 5.9, 95% CI 2.5 to 13.8, p<0.001). Frailty was a predictor of length of hospital stay and mortality, independent of age, gender and comorbidities.17

    Figure 2
    Figure 2

    The 30-day mortality (Panel A), 1-year mortality (Panel B) and clinical outcomes by frailty status.

    Previous studies have attempted to include frailty scores in the risk prediction models. Singh et al demonstrated that the addition of frailty, quality of life and Charlson Comorbidity Index to a conventional cardiovascular risk score (the Mayo Clinic Risk Score) improved the risk prediction for older patients undergoing PCI (C-statistic improved from 0.628 to 0.724, p=0.007).18 Another study evaluated self-reported Fried frailty score and GRACE score in 4996 patients aged over 65 years with ACS. After adjustment for baseline characteristics and GRACE covariates, frailty remained independently associated with the primary end point (composite of cardiovascular death, MI or stroke over a period of 30 months): pre-frail versus not-frail (HR 1.33, 95% CI 1.15 to 1.54; p<0.001); frail versus not-frail (HR 1.52, 95% CI 1.18 to 1.98; p=0.002).19 Thus, several studies have now demonstrated the importance of frailty in determining outcomes and provide additive prognostic information regarding future risk.

    Clinical frailty scoring is quick and easy to do at the bedside and is underused in routine cardiology practice. However, more research is needed to see if risk stratification by frailty aids invasive management decisions in older patients. While it is important to use frailty to define the risk, the important question is whether this risk is modifiable by intervention especially when much of the risk is attributable to frailty.

    Potential benefits of invasive strategy among older patients with NSTEACS

    Improvement in clinical outcomes-data from registries

    Although the use of an invasive strategy offers the greatest relative benefit to younger patients, it offers the greatest absolute benefit to those over 75 years; within each age group, the 1-year mortality rate was lower in those who underwent PCI compared with those who did not (≤65 years: 1.6% vs 4.9%; 65–74 years: 4.9% vs 10.5%; ≥75 years: 11.6% vs 21.8%; p<0.001).3 In an analysis of the Polish Registry of Acute Coronary Syndromes of 13 707 patients aged ≥80 years, invasively managed patients had a higher rate of major bleeding but lower rates of MI and in-hospital, 30-day, 6-month, 1-year and 2-year mortality compared with propensity score-matched patients who were managed conservatively. The rate of stroke was not different between the two groups. Over the course of the study, the rate of PCI for NSTEACS in older patients did increase from 7% in 2003 to 37% in 2009 (p<0.0001).20 In another analysis, De Luca et al analysed data from five consecutive Italian nationwide registries of patients with non-ST elevation myocardial infarction (NSTEMI), conducted between 2001 and 2010. In their analysis, an invasive approach increased from 26.6% in 2001 to 68.4% in 2010 (p<0.0001) and revascularisation rates increased from 9.9% to 51.7% (p<0.0001). Overall, 30-day observed mortality decreased from 14.6% to 9.5%.21

    Improvement in clinical outcomes: data from RCTs

    Despite the growing ageing population, only one post-hoc analysis of a RCT22 and two small RCTs have evaluated the benefit of invasive versus conservative treatment in older patients with NSTEACS. In the study by Bach et al, among patients aged ≥65 years, the early invasive strategy compared with the conservative strategy yielded a 4.8% absolute reduction in death or MI at 6 months (8.8% vs 13.6%; p=0.018). Among patients older than 75 years of age, there was 10.8% reduction in death or MI at 6 months in the early invasive strategy (10.8% vs 21.6%; p=0.016) with an increase in major bleeding rates (16.6% vs 6.5%; p=0.009).22

    In an Italian cohort, Savonitto et al23 randomised 313 patients (mean age 82 years) with NSTEACS to either early (<72 h) angiography or an initial conservative strategy, where angiography was only allowed in the case of ischaemia refractory to medical therapy, reinfarction, ischaemic heart failure or ventricular arrhythmia. There was a significant reduction in early recurrent ischaemia (0.6% vs 9.4%, p=0.0004), although only patients with an elevated baseline troponin had a reduction in the 1-year primary composite end point of all-cause mortality, MI, disabling stroke and repeat hospital stay for cardiovascular causes or severe bleeding (22% vs 40%, invasive vs conservative management respectively; p=0.03).23

    In a recent Norwegian trial of 457 patients over 80 years and presenting with NSTEACS, the primary composite end point of death, MI, need for urgent revascularisation and stroke was markedly reduced by an initial invasive strategy versus conservative strategy (41% vs 61%, p=0.0001). However, this study excluded high-risk frail patients, had no formal frailty assessment and the effect of treatment strategies on quality of life was not assessed. Importantly, 89% of eligible patients were not recruited into the study due to short life expectancy, ongoing or recent bleeding, inability to comply with study protocol, clinical instability including ongoing ischaemia, refusal to participate and ‘logistical and other reasons’. Moreover, 25% of patients did not have coronary stenosis on coronary angiography with only 52% of patients undergoing any form of revascularisation (PCI or coronary artery bypass grafting (CABG)), suggesting that this study consisted of a selected cohort of patients.24

    Improvement in quality of life

    Health-related quality of life (HRQoL) has been increasingly used as an indicator of health outcome in patients with chronic conditions including coronary artery disease (CAD).25 Interventions in older patients with CAD have been shown to be just as effective in improving HRQoL as they are in younger patients. A systematic review that identified 11 studies consisting of 700 octogenarian patients showed that HRQoL for octogenarians improved following PCI. Older patients improve at least as much as younger patients and may benefit more in the areas of physical functioning and improved angina status. The gain is greatest in the first 6 months but may continue until at least 3 years post intervention.26

    CABG versus PCI in older patients with ACS

    There are few studies examining the role of CABG in older patients with ACS. In a non-randomised prospective study of 249 patients aged ≥80 years with LMS disease (65.1% presented with ACS), patients who underwent CABG were more likely to have major adverse cardiac and cerebral events (MACCE) (defined as cardiac death, MI, repeat revascularisation and stroke/TIA) at 30 days than those who underwent PCI (28% vs 18%).27 However, after a mean follow-up of 23±16 months, the MACCE-free survival rates between the groups were similar (57% in the PCI group and 65% in the CABG group, p=0.33). In another retrospective study of 10 141 older patients with ACS with multi-vessel disease (mean age 87 years), higher mortality was noted in the early months after CABG compared with PCI (OR 1.48, 95% CI 1.34 to 1.64, p<0.01), but CABG provided lower mortality (OR 0.60, 95% CI 0.53 to 0.69, p<0.05) and freedom from composite outcome of death, repeat revascularisation, stroke and MI at 3 years (OR 0.83, 95% CI 0.76 to 0.91, p<0.01).28

    Treatment paradox

    Despite being a high-risk group, data from multiple global registries have consistently shown that older patients are much less likely to undergo invasive revascularisation following ACS. In an analysis of three international registries (GRACE and two Canadian registries: ACS I and ACS II), the rate of angiography following ACS decreased with age: 86% in patients aged ≤65 years, 80% in those aged 65–74 years and 57% in patients aged ≥75 years (p<0.001).3 In addition, older patients waited longer for angiography following ACS (≤65 years: 3 days, IQR 2–5; 65–74 years: 4 days, IQR 2–6; ≥75 years: 4 days, IQR 4–7; p<0.001).3 Physician-reported reasons given in the Canadian ACS II registry for not following an early invasive strategy included presence of significant comorbidities (16% of those ≥75 years vs 2% of those ≤65 years, p<0.001), patient or family refusal (10% vs 5%, p=0.01) and bleeding or safety concerns (9% vs 0%, p<0.001).3

    Potential risks of invasive care in older patients with ACS

    Risk of excess bleeding in older patients with ACS

    Older patients with ACS have a high risk of recurrent ischaemic events and cardiac death following PCI and have an increased risk of bleeding3 (figure 3). In a previous study, post-PCI bleeding is an important prognostic factor in patients >75 years of age. Bleeding improved the discriminatory power of multivariable model for mortality prediction (p=0.001). The risk of bleeding in this age category is increased in women and patients with impaired renal function.29 However, the excess bleeding could potentially be overcome by contemporary care in the current era of advanced interventional strategies and pharmacotherapy.

    Figure 3
    Figure 3

    Major bleeding rate by age and management strategy.

    Radial access procedures in older patients

    In patients with ACS undergoing invasive management, radial access as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality.30 However, previous studies suggest that older patients are less likely to undergo PCI via transradial access. In a study consisting of patients treated in the UK, adoption of the transradial access ranged from 43% in patients aged <60 years to 39% in patients aged ≥80 years (p<0.0001).31 In this cohort, usage of transradial access was also associated with decreased 30-day mortality in all age groups.31

    Use of novel antiplatelet agents in older patients with ACS

    Among older patients aged ≥75 years, due to increased risk of fatal and intracranial haemorrhage, the third-generation thienopyridine prasugrel is not recommended for use.32 In a sub-study of the PLATelet inhibition and patient Outcomes (PLATO) trial, Husted et al examined the clinical outcomes in older (≥75 years) versus younger patients treated with the other novel antiplatelet agent, ticagrelor versus clopidogrel.33 The clinical benefit of ticagrelor over clopidogrel was similar between older and younger patients with respect to the primary composite outcome of cardiovascular death, MI or stroke (p for interaction, 0.56) and ticagrelor was nominally more effective than clopidogrel in reducing all-cause mortality for all age categories (calculated using 5-year categorical age ranges). There were no differences in overall major bleeding rates between age groups with either ticagrelor or clopidogrel (p=0.89).33 However, non-procedure-related major or minor bleeding was increased in the ticagrelor group (5.9% vs 4.3%, p<0.0001), and this was mainly driven by bleeding occurring after 30 days in the ticagrelor group.34 However, in another analysis, there was no benefit with ticagrelor in NSTEMI patients undergoing revascularisation (interaction p<0.01 vs patients <65 years old).35 Given the association of reduced bleeding, the lower dose of 60 mg twice daily of ticagrelor may therefore be sufficient in older patients following ACS.36 Moreover, recent studies suggest short duration antiplatelet therapy might lead to reduced bleeding without increase in ischaemic events.37 ,38 Detailed overview of all pharmacotherapy agents among older patients with NSTEMI is beyond the scope of this review and was previously well addressed in a recent expert position paper of the European Society of Cardiology working group on thrombosis.39

    PCI in older patients with concomitant use of oral anticoagulants

    Older patients who present with ACS often have other comorbidities such as atrial fibrillation or valvular disease that mandates oral anticoagulation. Dual antiplatelet therapy plus an oral anticoagulant confers a high annual bleeding risk (16% in one large registry study).40 There have been no studies specifically evaluating oral anticoagulants in older patients post-PCI for ACS, but the What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing (WOEST) study demonstrated that patients assigned to clopidogrel and oral anticoagulant had fewer bleeding events and a reduction in the combined secondary end point (death, MI, stroke, target vessel revascularisation and stent thrombosis) compared with patients receiving triple therapy.41 However, only a quarter of patients in the WOEST trial presented with ACS, and the mean age of the cohort was only 70 years, with patients >80 years of age excluded from participation. The updated European Society of Cardiology guidelines recommend the use of triple therapy following PCI for 1 month.42 Careful evaluation of thrombotic and bleeding risks should be performed using CHA2DS2 VASc and HAS-BLED scores.42 Data from studies evaluating novel oral anticoagulants in this setting are awaited.

    PCI in older patients with renal dysfunction

    The prevalence of chronic kidney disease (CKD) increases with age and CKD is an independent predictor of mortality following NSTEACS.43 Renal function and perfusion to kidneys are reduced in older patients with alteration in nephron histology. Moreover, in the setting of a chronically reduced renal function, conditions such as NSTEMI occurring concurrently may also lead to rapid further deterioration in creatinine clearance in older patients. This will have implications on the clearance of drugs in particular the antithrombotic drugs that are primarily cleared by the kidneys such as low-molecular-weight heparins, fondaparinux, bivalirudin, dabigatran, eptifibatide and tirofiban.44

    In an analysis of the Italian ACS study cohort (enrolling 306 patients with NSTEACS ≥75 years of age), 32% of patients had a creatinine clearance value of <45 mL/min.45 One-year mortality was worst in patients with renal dysfunction and no revascularisation versus those with renal dysfunction that were revascularised versus those with normal renal function that were revascularised (23% vs 13% vs 5% respectively).45 Recent data demonstrate that the estimated survival benefit from revascularisation did not change across the range of renal function, except in those patients with a creatinine clearance of <30 mL/min, in whom the estimated survival benefit was more conservative but still present (OR 0.59).43

    Complex coronary anatomy in older patients

    Older patients with ACS have more complex disease than younger patients (table 4). Because of this increased complexity of coronary disease, procedural success is lower in older patients perhaps because of the higher rate of undelivered stents (9.4% vs 4.0%, p<0.001).10 In addition, the coronary vessels of older patients are frequently calcified (85% of lesions in one series of nonagenarians undergoing PCI) with an increase in target lesion calcium with increasing age (figure 4).46 There are few data available on the use of calcium debulking techniques, such as rotational atherectomy, in older patients but in one registry of 218 patients, age >70 years was not a predictor of all-cause mortality after rotablation (p=0.615).47

    View this table:
    Table 4

    Differences in the presentation of older and younger patients with NSTEACS

    Figure 4
    Figure 4

    Pattern of coronary artery disease in the older patient with acute coronary syndrome.

    Intravascular imaging has allowed a greater insight into the underlying plaque composition in patients with ACS as demonstrated by the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study which consisted of 697 patients with ACS who underwent virtual histology intravascular ultrasound (IVUS) in all three epicardial coronary vessels.48 Patients ≥65 years of age had a similar number of non-culprit lesions as younger patients but the plaque volume was slightly higher in the older group.48 In addition, older patients had a higher burden of dense calcium on virtual histology-IVUS (6.9% vs 4.6%, p<0.0001).48

    PCI strategy in older patients with ACS

    In an effort to reduce peri-procedural complications in older patients with ACS, it has been suggested that an incomplete revascularisation strategy may be preferable in this high-risk cohort with multivessel disease and complex comorbidities. A prospective single-centre observational study followed 502 patients ≥75 years of age who presented with ACS and multivessel disease and who underwent either complete or incomplete revascularisation.49 There was no difference in major adverse cardiovascular and cerebral events (MACCE: cardiac death, non-fatal acute MI, target lesion/target vessel revascularisation and cerebral artery events) between the two groups after a median follow-up of 36 months (20.4% in the incomplete revascularisation group vs 14.9% in the complete revascularisation group, p=0.141).49 However, there was a higher mortality rate in the incomplete revascularisation group both in-hospital (2.9% vs 1.3%, p<0.0001) and at follow-up (13.6% vs 7.7%, p=0.05).49 This may be due to the fact that the incomplete revascularisation group had a higher incidence of multivessel disease and a higher SYNTAX score, and patients in the complete revascularisation group that had failed PCI (n=21) were transferred into the incomplete revascularisation cohort. It is not clear whether culprit-vessel-only PCI is a better strategy in older patients with NSTEACS and requires further study.

    A holistic approach to revascularisation in older patients with ACS

    The current European Society of Cardiology guidelines on the management of NSTEACS advocate a personalised and holistic approach to invasive revascularisation in the elderly, emphasising that treatment decisions in this age group should be made in the context of careful evaluation of potential risks and benefits, estimated life expectancy, comorbidities, quality of life, frailty and patient values and preferences.42 ,50 However, these recommendations are based on level C evidence, and further research is needed, particularly with regard to quality of life after PCI. The European guidelines also recommend that older patients should be considered for an early invasive strategy, a class IIa recommendation.50 The joint American College of Cardiology and American Heart Association guidelines do not make any specific recommendations for PCI after ACS in older patients, instead stating that, although older patients are at higher risk of adverse events after PCI, the absolute benefit of PCI is greater.51 A suggested algorithm for the management of older patients with NSTEACS based on current knowledge on this topic is shown in figure 5.

    Figure 5
    Figure 5

    Algorithm for the management of older patients with NSTEMI. CV, cardiovascular; EQ5D, EuroQOL 5D.

    Future directions

    As our population ages, the burden of ACS in complex older patients (and especially NSTEACS) is on the rise. There is a dearth of good quality RCTs comparing contemporary treatments in older patients and the benefits of incomplete versus complete revascularisation, use of pharmacotherapy and CABG are unclear. A new study called the OLD-RITA study has been designed to determine if a routine invasive strategy reduces overall 1-year mortality compared with a conservative treatment strategy in older patients (≥75 years) with NSTEMI. This study will particularly use frailty score to identify, to characterise and to investigate at-risk older patients presenting with NSTEMI.

    This study will also consist of inclusion of all-comer older patients with NSTEMI including those with comorbidities and those with cognitive impairment who normally would be denied invasive care due to underlying comorbidity and in whom there is lack of evidence currently in the management of NSTEMI.

    Acknowledgments

    The research is supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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    Footnotes

    • Correction notice Since this paper was first published online figure 5 has been updated. All instances of CMT have been updated to OMT.

    • Contributors HS wrote the initial draft manuscript. VK critically reviewed, substantially revised and edited the manuscript.

    • Funding British Heart Foundation Clinical study grant for OLD-RITA trial CS/15/7/31679.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; externally peer reviewed.