ACS remain one of the most common reasons for hospital admission worldwide. Enthusiasm in recent times has centred on identification of the high risk patient, with trial evidence showing a benefit of early interventional based treatment in this population.6,10,11
Troponin status and the presence or absence of dynamic ECG changes remain the most widely used aids for the risk stratification of patients on presentation,6,10,11
and this approach has been widely promulgated in international guidelines.1,2
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
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
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
Study strengths and limitations
GRACE is the largest ongoing multinational registry to include the complete spectrum of ACS patients. In addition, GRACE employs standardised criteria for defining ACS and hospital outcomes and the most rigorous quality control and audit measures of any ongoing or previously published registry dataset. A limitation that can apply to registries of this nature is that the information provided is often extracted from the medical record, requiring second hand interpretation by the study coordinator or physician. However, high risk features of presentation with ACS, which were crucial to the stratification in this analysis, are almost invariably well documented in the medical record and were therefore unlikely to be subject to misinterpretation.
Patients presenting with lower risk features in GRACE have a low incidence of death and myocardial infarction in hospital. However, recurrent ischaemia is just as frequent in this population as in high risk patients. The use of non-invasive testing for further risk stratification is low despite recommendations in current practice guidelines. Angiography is used for risk stratification in a significant proportion of patients, but more than a third do not undergo any form of risk stratification while in hospital. Approaches to further risk stratification and management strategies are similar between lower risk and high risk populations, with revascularisation procedures performed almost as often in the two groups. Patients are often given less than optimal treatment on discharge, and in the six months after discharge lower risk patients are as likely as high risk patients to present again with a cardiac related condition. Our global data show that risk assessment strategies are not applied sufficiently often to patients with ACS regardless of their presenting characteristics. It remains to be seen whether wider application of more accurate risk stratification tools will have an impact on evidence based application of invasive or non-invasive strategies after admission.