Patients: The study was based on 11 885 consecutive patients presenting with non-ST segment elevation ACS enrolled in GRACE (global registry of acute coronary events). Patients without dynamic ST segment changes, positive troponin (or other cardiac markers), or haemodynamic or arrhythmic instability were defined as being at lower risk.

Main outcome measures: Management and outcomes were compared with high risk presentations.

Results: Of 11 885 patients presenting with unstable angina or non-ST segment elevation myocardial infarction, 4252 (36%) were regarded as being at lower risk. Functional testing for risk stratification was performed in 1163 of 4207 (28%) lower risk and 1531 of 7521 (20%) high risk patients (p < 0.0001). Coronary angiography was performed in 1930 of 4190 (46%) and 3860 of 7544 (51%), and echocardiography in 1692 of 4190 (40%) and 4348 of 7533 (58%) of lower risk and high risk patients, respectively (p < 0.0001 for both). Over one third of patients did not undergo further risk assessment with angiography or functional testing (2746 of 7437 (37%) high risk, 1499 of 4148 (36%) lower risk, not significant). Death occurring in hospital was more likely in the high risk cohort (41 of 4227 (1.0%) lower risk v 215 of 7586 (2.8%) high risk, p < 0.0001), whereas rates of recurrent angina during admission and readmission were similar in both groups (1354 of 4231 (32%) high risk, 2313 of 7587 (31%) lower risk, not significant). In the six months after discharge, death or myocardial infarction occurred in 79 of 3223 (2.5%) lower risk patients and 302 of 5451 (5.5%) high risk patients (p < 0.0001).

“Low risk” does not mean “no risk”, with a three year cardiac event rate as high as 12% being noted in troponin negative patients in selected study populations.³ However, the incidence of events in a lower risk population has not been well described in patients routinely encountered in clinical practice.

The most commonly applied methods of risk stratification include identification of patients with haemodynamic instability, dynamic ECG changes, or increases in serum enzymes such as troponin. Troponin assays play an integral part in risk stratification, with troponin positive patients noted to be at higher risk of subsequent events. These events can be reduced by the use of glycoprotein IIb/IIIa antagonists, low molecular weight heparins (LMWHs), and early revascularisation strategies.^4–6 Although multivariable models derived from clinical trial datasets such as the TIMI (thrombolysis in myocardial infarction) risk score have been used to develop global assessments of risk,⁵ currently most clinicians use simple criteria such as troponin rise and ST segment change on an ECG to identify high risk patients. We therefore determined how reliably these criteria identified patients at greatest likelihood of an event by quantifying the risk among the lower risk population. A secondary goal was to document approaches to further risk stratification and management strategies in this lower risk group: risk assessment, management practices, and outcomes were compared with those in the high risk population.

To ensure the enrolment of an unbiased population, the first 10–20 consecutive patients (depending on each site’s patient throughput) were recruited from each site every month. Patients entered in the registry had to be at least 18 years old and alive at the time of hospital presentation, be admitted for ACS as a presumptive diagnosis (that is, have symptoms consistent with acute ischaemia), and have at least one of the following: ECG changes consistent with ACS, serial increases in serum biochemical markers of cardiac necrosis, and documentation of coronary artery disease. The qualifying ACS must not have been precipitated or accompanied by a significant non-cardiovascular co-morbidity, trauma, or surgery. At about six months after hospital discharge, patients were followed up to ascertain the occurrence of selected long term study outcomes. Where required, study investigators received approval from their local hospital ethics or institutional review board.

Trained coordinators collected data on standardised case report forms. Demographic characteristics, medical history, presenting symptoms, duration of pre-hospital delay, biochemical and ECG findings, treatment practices, and a variety of hospital outcome data were collected (full definitions are provided at www.outcomes.org/grace). Standardised definitions of all patient related variables and clinical diagnoses were used. Standardised definitions were also used for selected hospital complications and outcomes.⁸

Patients presenting with ST segment elevation myocardial infarction or new left bundle branch block were excluded from this study. Lower risk was defined as unstable angina as the discharge diagnosis in the absence of dynamic ST segment changes, positive troponin assay (or other cardiac markers), and haemodynamic or arrhythmic instability. High risk patients had one or more of the above features noted on presentation.

There are more involved techniques for estimation of risk than those selected for this analysis. One method promoted in the ACC/AHA guidelines involves the TIMI risk score.⁵ The seven variables in this score are age 65 years or older, at least three risk factors for coronary artery disease, prior coronary stenosis of 50% or greater, ST segment changes on presentation, at least two anginal events in the preceding 24 hours, use of aspirin in the previous seven days, and increased cardiac markers. Risk increases in parallel with TIMI score, with a major adverse cardiac event at 14 days noted in 41% of patients in the TIMI 11B trial with a TIMI risk score of 6 or 7.⁵ Recently, Granger et al,¹² for the GRACE investigators, reported a new risk assessment model based on the spectrum of patients with ACS seen in everyday practice. Eight independent risk factors were assessed and they included, for the first time, two variables not previously identified from clinical trial databases: baseline creatinine concentration and cardiac arrest at presentation. This GRACE model is an excellent tool for assessing the risk for death and can be used as a simple nomogram to estimate risk in individual patients, with the advantage of general applicability across the full spectrum of ACS.¹²

Both the TIMI and GRACE risk scores are best applied when the clinician has access to a personal digital assistant. This is not commonplace internationally; the TIMI score is not widely applied in clinical practice outside the USA. Furthermore, there is no evidence to date that application of risk scores such as these will result in improved patient outcomes when compared with simple bedside risk stratification based on troponin status and the presence or absence of dynamic ECG changes.

Our study focused on the clinically identified lower risk population. Stubbs et al³ noted a three year rate of major cardiac adverse events of 12% in a low risk population defined as being troponin negative. Lindahl et al,¹³ for the FRISC (Fragmin and fast revascularisation during instability in coronary artery disease) study group, reported a lower risk of death or myocardial infarction of 4.3% with a shorter follow up period of five months. We found a similar event rate in our study population. In contrast to the FRISC group, however, we have presented additional information on readmission for cardiac related conditions. These were observed in almost 20% of our population, emphasising the burden these patients place on our health care systems.

Enrolment in GRACE requires symptoms consistent with a diagnosis of ischaemia plus one of the following: a history of known coronary artery disease, ECG changes consistent with ACS, or increased cardiac markers. The lower risk group in our study attained a calculated TIMI risk score of 2–4 and thus cannot be regarded as being at low risk. Event rates at 14 days of between 8.3% and 19.9% have been noted in patients with similar TIMI scores.⁵ Interestingly, patients with this risk profile have not been found to benefit consistently from the use of LMWHs, glycoprotein IIb/IIIa antagonists, and early intervention.^4–6 These treatments were offered to high risk patients only slightly more often, confirming reports that there is a deficiency of application of evidence based treatments across the spectrum of patients with ACS.^14,15

The use of non-invasive testing for ischaemia and assessment of left ventricular function to further risk stratify the lower risk population is recommended in European Society of Cardiology and ACC/AHA guidelines.^1,2 There is little evidence to suggest that this approach aids the further risk stratification of high risk ACS patients, yet, in our cohort, one in five high risk patients underwent stress testing. Presumably this reflects limitations on access to catheterisation laboratories because patients from a number of sites without catheterisation facilities were enrolled in GRACE. Conversely, prognostic assessment with stress testing was undertaken in only 1163 of 4207 (28%) of the lower risk cohort in GRACE, which is the population that is likely to benefit from further risk assessment.¹⁶ There was a relatively high incidence of angiography (1930 of 4190 (46%)) in this population, with recurrent angina noted in about half of the lower risk population who underwent angiography. Thus, it appears that a significant proportion of lower risk patients underwent angiography that was not ischaemia driven, suggesting that angiography may be used as an aid to risk stratify the lower risk cohort in some centres. Nonetheless, more than a third of these patients did not undergo any form of risk stratification, either stress testing or coronary angiography, after admission. It is worth noting that these patients had a greater prevalence of known coronary disease than the higher risk population; it is possible, therefore, that coronary ischaemia had been assessed previously and was therefore not required on this occasion. Interestingly, though, a similar proportion of high risk patients did not undergo any further risk stratification or followed a non-invasive management pathway, despite the evidence of the incremental benefit of coronary angiography in this population.

More of the lower risk group were taking antianginal agents on discharge. Of some concern is that β blockers, which should be regarded as the first line antianginal treatment of choice unless contraindicated, were not prescribed to nearly one third of patients in both groups at discharge.

By six months after discharge from hospital, mortality (79 of 3223 (2.5%)) in the lower risk cohort was appreciable, although lower than in high risk patients. Readmission rates were similar in both groups, with one in five patients presenting again with a cardiac related problem, emphasising the burden these patients place on health care systems. The performance of coronary angioplasty was predictive of readmission and was most likely related to restenosis. One would anticipate that the application of drug eluting stents will affect readmission rates in this population. GRACE will be positioned to audit this prospectively.

Factors that were associated with a reduced likelihood of readmission included the prescription of aspirin at discharge and the performance of coronary artery bypass grafting. The protective effect of aspirin has recently been documented in GRACE, with less severe clinical presentation and better outcome in patients presenting with ACS who were previously taking aspirin.¹⁷