We compared the rates of cardiac catheterization in 2136 non–ST-segment elevation acute coronary syndrome patients who were stratified according to their baseline thrombolysis in myocardial infarction (TIMI) risk score. Higher-risk patients were referred for catheterization at a similar rate as low-risk patients. The main reasons why physicians did not make referrals included (1) clinical trial evidence did not support an early invasive approach and (2) 68% of patients were thought not to be at high enough risk; however, 59% of these patients were found to be higher risk when their baseline TIMI risk scores were recalculated. Patients who were referred for catheterization had better in-hospital and 1-year outcomes. Our findings indicate that a significant opportunity remains to improve upon accurate risk stratification and adherence to an early invasive strategy for higher-risk patients.
The prompt use of cardiac catheterization plays an important role in the contemporary treatment of patients with non—ST-segment elevation (NSTE) acute coronary syndrome (ACS). This “early invasive strategy” is supported by several randomized clinical trials1-3 and is recommended by current evidence-based guidelines for patients with high-risk clinical features.4-7 Despite this, the use of cardiac catheterization is not optimal; factors such as geographic variation, hospital attributes, and patient demographics contribute to the evidence-to-practice gap.8-10 We aimed to explore the appropriateness and timeliness of referral for in-hospital cardiac catheterization, the reasons why some patients were not referred, and the relationship between an early invasive strategy and 1-year outcomes.
Subjects and methods
The Canadian ACS Registry II was a prospective, multicenter, observational study of the clinical characteristics, management, and outcomes of 2359 patients who presented with NSTE-ACS to 36 hospitals throughout 7 provinces between October 1, 2002 and December 31, 2003. Data were collected and recorded on standardized paper case-report forms submitted by the treating physician. We included 2136 patient records that contained all the data required for calculating the Thrombolysis in Myocardial Infarction (TIMI) risk score for unstable angina/NSTE myocardial infarction; this composite score uses 7 equally weighted predictor variables.11 Patients were divided into the following risk categories for analysis: low risk (TIMI risk score, 0-2), intermediate risk (TIMI risk score, 3-4), and high risk (TIMI risk score, 5-7). Categorical data are reported as frequencies and percentages, and continuous variables are reported as median and interquartile ranges (IQR). Kruskal-Wallis (or Mann-Whitney) and chi-square tests were used to compare differences in continuous and categorical variables across patient groups, respectively. A 2-sided P value of ≤.05 was considered statistically significant.
Baseline demographic data and presenting clinical characteristics of patients based on TIMI risk category are presented in Table 1. The gradients we observed in age and prevalence of hypertension, diabetes mellitus, hyperlipidemia, preexisting coronary artery disease, previous revascularizations, congestive heart failure, ST-segment depression, and positive cardiac markers were consistent with progressively higher TIMI risk categories. Almost two-thirds (64.7%) of the 2136 patients were referred for cardiac catheterization during the index admission. There was no difference in the mean (standard deviation [SD]) TIMI risk score for patients who underwent cardiac catheterization compared with those who did not: 2.99 (1.38) versus 3.11 (1.41), respectively (P = .07). There was also no statistically significant difference between the rate of referrals made for cardiac catheterization among the low-, intermediate-, and high-risk groups, with rates of 66.9%, 63.7%, and 62.5%, respectively (P = .25). The median waiting times for patients receiving catheterization were similar between all groups (P = .18), with low-risk and intermediate-risk patients having a wait of 3 days (IQR, 2-6 days) and high-risk patients having a wait of 4 days (IQR, 2-6 days). Rates of referral were significantly higher if patients were cared for by a cardiologist compared with a noncardiologist (77.0% vs 67.6%; P ≤.001) and for hospitals with on-site catheterization facilities versus those without (75.6% vs 58.6%; P≤.001).
If a patient was not referred for in-hospital cardiac catheterization (n = 754), the treating physician was asked to provide the primary reason why (Table 2). The most frequently reported reason, used for 516 patients (68.4%), was that the patient was not at high enough risk to warrant this intervention or that clinical trial evidence did not support the strategy. Of these patients, 305 (59.1%) were actually calculated to have higher TIMI scores (TIMI risk score, 3-7). Cardiologists and noncardiologists were equally likely not to refer patients because of perceived lower risk (41.6% vs 38.5%; P = .43).
Patients who underwent cardiac catheterization had a statistically significant lower in-hospital and 1-year all-cause mortality rate than those who did not, with rates of 0.8% versus 3.7% (P ≤.001) and 4.0% versus 10.9% (P ≤.001), respectively (Figure). When this analysis was restricted to patients who had higher TIMI risk scores (TIMI risk score, 3-7), the difference in in-hospital and 1-year mortality rates remained statistically significant, with patients undergoing cardiac catheterization having lower rates of 1.0% versus 4.8% (P ≤.001) and 5.6% versus 14.3% (P ≤.001), respectively.
Higher-risk patients (TIMI risk score, 3-7), who were not referred for cardiac catheterization because they were perceived not to be at high enough risk had significantly worse outcomes, including a higher 1-year mortality rate than similar higher-risk patients (TIMI risk score, 3-7) who received in-hospital cardiac catheterization (9.1% vs 5.6%; P = .04). An analysis using the same patient population and the Global Registry of Acute Coronary Events (GRACE) score12 showed similar results.
The results of our study indicate that there remains a significant opportunity to improve upon accurate risk stratification and adherence to an early invasive strategy for higher-risk patients, which has been endorsed by the most recent American College of Cardiology/American Heart Association practice guidelines.5 In our study, of the patients who presented with NSTE-ACS, approximately two-thirds were referred for cardiac catheterization during index hospitalization. Higher-risk patients underwent cardiac catheterization at a similar rate and within the same time frame as lower-risk patients. Consistent with both clinical trial1-3 and “real-world” populations,9,13 we observed lower in-hospital and 1-year mortality rates among higher-risk patients undergoing cardiac catheterization during the index hospitalization. We also found that the rate and timing of in-hospital cardiac catheterization were not different between low-risk patients and higher-risk patients, with the latter group being more likely to benefit from an early invasive strategy.
The disparity between guideline recommendations and the actual use of early invasive treatment strategies has been previously examined.14,15 The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) quality improvement initiative found that an early invasive strategy was implemented in only 45% of the high-risk patients presenting to hospitals capable of performing revascularization, and was more likely to be recommended by cardiologists and used in patients who were younger and had fewer comorbidities.9 This evidence-to-practice gap may in part be explained by a conscious decision by the physician, patient, or both, to specifically avoid cardiac catheterization because of the potential increased risks of treatment complications or morbidity (eg, renal dysfunction) that are often associated with higher cardiac risk.
Our study is different from others because it provided unique insights into why some patients were not referred for cardiac catheterization by gathering information and feedback directly from the treating physician. Although there were a variety of legitimate reasons for many patients not being referred, it is disconcerting that in more than two-thirds of cases where the treating physician thought that the patient was “not at high enough risk” to warrant this intervention, many of these patients (59.1%) actually had their risks underestimated. In these cases, when the patient’s baseline TIMI risk scores were recalculated, they were found to be at intermediate or high risk (TIMI risk score, 3-7). These results indicate that many higher-risk patients were denied the potential benefit of an early invasive strategy because of a misperception of their risk. Similar analyses with the GRACE risk score yielded the same information. The disparity between perceived risk and “real risk” (as measured by the TIMI and GRACE scores) may explain the evidence-to-practice gap that we observed.
While it is clear that treating physicians are underestimating risk, it is unclear which patient characteristics contribute to this underestimation. We hypothesize that physicians may be simply focusing on 1 or 2 risk factors, such as ST-segment depression or elevated cardiac markers, and are not considering other risk factors, such as advancing age.
Although our study attempted to capture and accurately reflect the real-world treatment of patients, it had some limitations. First, sites recruited to participate were not randomly selected or population-based; thus, patients do not necessarily represent a random selection. The methods for data collection might have limited the inclusion of patients who died before or shortly after hospital admission, thereby limiting the ability to generalize our findings. Physicians were also asked to choose from a checklist of potential reasons for not referring patients for cardiac catheterization; thus, there may have been reasons that were not captured because they were not on the checklist. Nevertheless, these limitations could not account for the failure of treating physicians to recognize the high-risk features in most patients.
There is an evidence-to-practice gap that exists in patients who present with NSTE-ACS. Many of these patients are not being appropriately referred for cardiac catheterization because of the misperception that they do not have high enough cardiac risk to warrant an early invasive strategy, resulting in worse outcomes in those denied this treatment. There remains a significant opportunity to improve on accurate risk stratification and adherence to an early invasive treatment strategy for higher-risk patients, which has been shown to be beneficial.
Dr Lee has no conflicts of interest. Dr Goodman has received research grant support and speaker/consulting honoraria from Sanofi Aventis and Pfizer (co-sponsors of the Canadian ACS Registry II).