QJM Advance Access originally published online on July 28, 2006
QJM 2006 99(9):601-607; doi:10.1093/qjmed/hcl079
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Admission ECG predicts long-term outcome in acute coronary syndromes without ST elevation
From the 1Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust, London, 2Chelsea and Westminster Healthcare NHS Trust, London, 3Barnet and Chase Farm NHS Trust, London, 4Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, and 5National Heart and Lung Institute, Imperial College School of Medicine, London, UK
Address correspondence to Dr J. Collinson, Department of Cardiology, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH. email: julian.collinson{at}chelwest.nhs.uk
Received 24 January 2006 and in revised form 17 May 2006
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Summary |
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 Top Summary IntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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Background: Acute coronary syndromes (ACS) without ST elevation are a frequent cause of hospital admission, myocardial infarction and death.
Aim: To explore the role of the ECG in stratifying ACS patients.
Design: Prospective, centrally-coordinated multicentre registry involving 56 centres throughout the UK.
Methods: Consecutive patients admitted with ACS without ST elevation on the presenting ECG (n = 1046) were followed for 6 months. A subgroup (n = 653) were flagged with the UK Office for National Statistics and followed-up for death over 4 years.
Results: Mean follow-up for the group as a whole was 2.4 years. In the first 6 months, the death rate was 7.3%. Survival at 1 year was 90.8% (95%CI 88.2%–92.8%); at 45 months it was 77.8% (95%CI 74.1%–81.1%). We compared data in those with ST depression or bundle branch block on the admission ECG (n = 304, 29%) with those with T wave inversion, Q waves and minor ST segment changes (n = 576, 55%) and those with a normal ECG (n = 166, 16%). Their respective incidences of death were 15%, 5% and 2% (p < 0.01) at 6 months, and 38%, 22% and 7% (p < 0.01) at 4 years.
Discussion: Rates of adverse events are high in patients admitted to UK hospitals with ACS without ST elevation. The ECG remains a very important and simple discriminator of both short- and long-term risk, enabling more aggressive, proven therapies to be targeted towards those at highest risk.
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Introduction |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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Acute coronary syndromes (ACS) without ST elevation are a frequent cause of hospital admission, myocardial infarction and death1. Over the past few years, many evidence-based therapies have become available, including more powerful platelet therapies2,3 and more aggressive strategies of revascularization. Coupled with this, there has been a greater emphasis on the risk stratification of patients, enabling the targeting of these more expensive and technically advanced treatments towards those at highest risk.4,5
We undertook the Prospective Registry of Acute Ischaemic Syndromes in the UK (PRAIS-UK) to determine characteristics, practice patterns, outcomes and important markers of risk of patients admitted to a wide range of UK hospitals with ACS without ST elevation. Patients with abnormalities on the admission ECG were demonstrated to be at high risk. Therefore, we undertook a more detailed analysis at the role of ECG-based risk stratification and the effect of high-risk admission ECG on subsequent management and outcomes.
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Methods |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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PRAIS UK is a prospective observational cohort registry of patients admitted to 56 UK hospitals with acute coronary syndromes without ST elevation. Between May 1998 and Feb 1999, 1046 patients with non-ST elevation ACS were enrolled.6 Each participating hospital was requested to enrol 20 consecutive eligible patients and follow them up for 6 months. Eligible patients had to have a clinical history of ACS with either ECG changes consistent with acute myocardial ischaemia, or with prior evidence of coronary artery disease (e.g. prior myocardial infarction, prior revascularization). Patients with persistent ST elevation or receiving thrombolysis were excluded. The study was carried out with 6 months follow-up after index hospital admission. The study received national and local ethical approvals, and each patient provided informed consent.
The decision to perform long-term follow up was taken 3 months after starting enrolment in PRAIS-UK. Although Multicentre Research Ethics Committee approval for long-term follow-up was obtained for all centres, local approvals could only be requested from hospitals that were still enrolling patients, or those that had not yet started enrolment. Local ethical approvals were eventually obtained in 34 out of the 56 hospitals that enrolled a total of 653 patients with 100% mortality follow-up at 6 months. Of these, 490 patients gave consent for long-term mortality follow-up.
The Office of National Statistics (ONS) for England, Wales and Northern Ireland, and the General Register Office (GRO) of Scotland provided vital status as of 15 November 2002. Dates of death and copies of death certificates were also provided.
Outcomes of interest included death, new myocardial infarction (MI), refractory angina and re-admission with unstable angina. The definition of new MI required at least two of the following: (i) new severe cardiac chest pain; (ii) creatinine kinase (CK) or other cardiac enzyme rise to twice the upper limit normal; (iii) new ECG changes (either prolonged ST elevation or new Q waves). Refractory angina was defined as new cardiac chest pain in hospital with associated ECG changes consistent with ischaemia lasting at least 5 min, despite optimal medical therapy (including intravenous nitrates), and leading to either thrombolysis for threatened MI, insertion of an intra-aortic balloon pump or revascularization within 7 days of its onset. A multivariate analysis was performed to identify patient groups at high risk for death or MI.
Investigators were asked to classify the admission ECG prospectively at baseline into the following categories: (i) ST depression—at least 1 mm in two or more contiguous leads, or right or left bundle branch block (BBB); (ii) T wave inversion, Q waves including other ST segment or T wave changes (T inversion); (iii) normal ECG—none of the above abnormalities. Bundle branch block was included with ST depression, as they both represented the higher risk ECG categories and only 10% of patients had BBB at baseline.
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Statistics |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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Analyses used the STATA software. Continuous risk factors were described as means ± SD, categorical variables as number of patients and percentage. The Cox proportional hazards model was used to assess the impact of the selected risk factors on the survival of patients based on all 653 patients.7 Assessment of the assumption of proportionality for a significant predictor was visually checked to see whether survival curves tended to be parallel. In the Cox model analysis, p values <0.05 were considered significant. Kaplan-Meier plots were used to display the survival rates over the study period by selected categorical risk factors.
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Results |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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A total of 1046 patients were entered into the registry from 56 participating centres between 23 May 1998 and 3 February 1999. Data at 6 months were available for 1031 (99%) of the patients. There were 653 patients enrolled in hospitals with long-term follow-up. There were no significant differences in baseline characteristics between the original PRAIS-UK cohorts and this subset of 653 patients. The mean follow-up period for the overall cohort is 2.4 years.
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Baseline characteristics (Table 1) |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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Mean age at presentation was 66 ± 12 years, 61% were male, 16% had diabetes, 37% treated hypertension, 23% were current smokers, 48% had had a prior MI and 23% prior revascularization (either PTCA or CABG). The admission clinical diagnosis was unstable angina in 95% and MI without ST elevation in 5%. Based on cardiac enzyme elevation at hospital admission, 13.9% had MI associated with admission symptoms. Hazard ratios for long-term outcomes based on baseline characteristics are shown in Table 2.7
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Rates of major adverse outcomes |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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In the first 6 months, there were a total of 48 deaths (7.3%). Of these, 12 (1.8%) occurred in hospital and 36 (5.5%) in the period from discharge up to 6 months. There were further 84 deaths at final follow-up. The survival rate at 1 year was 90.8% (95%CI 88.2%–92.8%) and at 45 months 77.8% (95%CI 74.1%–81.1%). For the composite of death or new, non-fatal MI, the rates at 6 months were 5.0% and 12.2%. For the combination of death, MI, refractory angina or readmission for unstable angina, rates of events were 7.6% and 30.0% respectively.
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Outcomes by ECG category (Table 3) |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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We compared data in those with ST depression or bundle branch block on the admission ECG (n = 304, 29%) with those with ‘other’ changes (T wave inversion, Q waves, etc.) (n = 576, 55%) and those with a normal ECG (n = 166, 16%). In these groups, the proportions aged >70 years were 54%, 37% and 27% (p < 0.001), respectively. A prior history of heart failure as present in 21%, 12% and 5%, respectively (p < 0.01), diabetes in 23%, 14% and 13% (p < 0.01), hypertension in 41%, 37% and 31% (p = 0.08) and a prior history of MI in 43%, 54% and 39% (p < 0.001). In-hospital heparin (either low molecular weight or intravenous unfractionated) was used in 79%, 78% and 69%, respectively (p = 0.02). At 6 months, there were no significant differences in the use of aspirin (79% overall), beta-blockers (42%) or statins (46%) in the three ECG groups. By this time, angiography had been performed in 28%, 28% and 24%, respectively (p = 0.3) and revascularization in 17%, 15% and 11% (p < 0.01).
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At 6 months, the incidences of death were 15%, 5% and 2%, respectively (p < 0.01) and incidences of the composite of death or new MI were 22%, 9% and 6% (p < 0.01). After 4 years, death occurred in 38%, 22% and 7%, respectively (p < 0.01) (Figure 1).
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Bundle branch block |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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On the admission ECG, 10% of patients had bundle branch block (BBB). Death or new MI occurred in 30% of patients with BBB, vs. 11% of those without BBB at 6 months (OR 2.63, 95%CI 1.60–4.32 in a multivariate analysis, p < 0.001). The composite of death or new MI at 6 months was higher for patients with left BBB (36%) than for those with right BBB (23%) or ST depression (19%) (p < 0.001).
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Discussion |
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TopSummaryIntroductionMethodsStatisticsResultsBaseline characteristics (Table...Rates of major adverse...Outcomes by ECG category...Bundle branch blockDiscussionAcknowledgementsReferences |
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Rates of adverse events are high in patients admitted to UK hospitals with ACS without ST elevation. Our study shows that in the context of non-ST elevation ACS, the ECG remains a very important and simple discriminator of short and long-term risk. A normal ECG in the face of a history of ACS is associated with a similar risk of death to a ‘normal’ unselected population (estimated risk of death per annum in 1999 was 1.1% for males and 0.7% for females aged 55–64 years, and 3.2% and 1.9%, respectively, for those aged 65–74 years).8 ECG changes such as ST depression are well known to be associated with adverse outcomes in these patients, and provide an easy method for identifying high-risk patients.9 Those with either right or left BBB have a particularly high short-term risk, but numbers in our study were too small to indicate if this continues long-term. Other accepted methods for risk stratification in these patients, such as troponin and stress testing add predictive value, but were used infrequently in this study. More recent studies have still validated the ECG as an independent prognostic tool, even with troponin routinely available.5 Other studies have shown similar results in the context of ST elevation MI, and shorter-term follow-up in non-ST-elevation ACS.10–12
Overall use of treatments such as aspirin, beta blockers and anti-thrombotic therapies was low in this study, despite clear evidence of efficacy. Use of lipid-lowering therapies was also low, although targets were less aggressive at the time of patient recruitment than currently. However, recently published data from the GRACE registry13 indicate that statin use remains low, despite studies demonstrating that higher doses of statins than those traditionally used are of benefit.14,15 At the time of recruitment of the majority of this cohort, the major guidelines about acute coronary syndromes had not been published, but there is evidence that adhering to these guidelines16–18 substantially improves prognosis.19,20 Audit-based strategies to improve compliance with guidelines have been tested in the UK and appear to be successful.21
The UK traditionally has low rates of revascularization,6,13 despite evidence that such strategies are associated with improved clinical outcomes,22 in particular in combination with glycoprotein IIb/IIIa inhibitors23 and improved patient quality of life.24 Our study suggests that these strategies are not always targeted towards those at highest risk. Other studies have demonstrated similar findings, with patients without significant co-morbidities and those seen by cardiologists being preferentially selected for an invasive approach.25 There is, in particular, evidence that a more aggressive approach in those aged >75 years substantially reduces ischaemic outcomes.26 ST depression is an independent prognostic risk factor for a poor outcome, but is often associated with other adverse risk factors such as heart failure, diabetes and myocardial infarction. It also appears that those with ST depression on admission benefit significantly from in-patient revascularization, with this benefit persisting at long-term follow-up.27,28 Patients presenting with suspected MI and LBBB are recommended for early reperfusion. In our study, about 7% of patients presented with LBBB but did not merit early reperfusion on clinical grounds. Bundle branch block in the context of ACS represents a high-risk category requiring aggressive management.
This study is limited by not having central validation of the admitting ECG, although all ECGs were categorized by experienced physicians in the admitting centres. Our data are based on patients treated in 1998–1999, and treatment patterns have generally become more intensive over the years. However, we believe our findings for the relative prognostic influence for different ECG categories remain valid, although absolute risks of death will vary over time and in different cohorts of patients.
The admission ECG for patients with ACS without ST elevation remains a powerful predictor of outcome,29 and is complementary to measurement of troponin.30 This study emphasizes the importance of the ECG in long-term risk stratification,5 and for targeting more aggressive, proven therapies towards those at highest risk.
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Acknowledgements |
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We are grateful to all investigators, research co-ordinators and acknowledge the support of Merck Sharp and Dohme for their original support for the PRAIS UK registry. The Clinical Trials and Evaluation Unit of the Royal Brompton Hospital funded the follow-up. We are also grateful to the Office of National Statistics of England and Wales, and General Registry Office (GRO) for Scotland for providing us with data on vital status and causes of death.
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References |
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