Cardiovascular risk and therapeutic benefit of coronary interventions for patients with unstable angina according to the troponin T status

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1 European Heart Journal (2000) 21, doi: /euhj , available online at on Cardiovascular risk and therapeutic benefit of coronary interventions for patients with unstable angina according to the troponin T status C. Heeschen 1, B. U. Goldmann 2, W. Terres 3 and C. W. Hamm 4 1 Stanford University School of Medicine, Division of Cardiovascular Medicine, California, U.S.A.; 2 Department of Cardiology, Hamburg University, 3 Department of Cardiology, General Hospital Celle, 4 Department of Cardiology, Kerckhoff-Clinic, Bad Nauheim, Germany Aims Elevation of troponin T in patients with unstable angina is predictive of adverse outcomes. Since no advanced therapeutic concept for such high-risk patients has been established, we investigated cardiac risk prior to, during, and after coronary revascularization in patients with unstable angina stratified according to the troponin T status. Methods and Results Out of 351 patients with unstable angina, troponin was elevated for 36% of the patients as determined by qualitative bedside tests. The patients were followed during hospitalization and 30 days after discharge for incidence of death and myocardial infarction. In troponin-positive patients, clinical symptoms were more refractory to medical treatment than in troponin-negative patients (78% vs 44%; P=0 002). Although these patients were catheterized earlier (1 6 vs 3 4 days; P=0 005) and more frequently (95% vs 69%; P<0 001), troponin-positive patients suffered a higher incidence of cardiac events prior to scheduled revascularization (death, myocardial infarction; 6 4% vs 0 4%; P<0 001). The angiogram for troponinpositive patients confirmed a more severe coronary artery disease requiring revascularization (69% vs 50%; P=0 001). Also the following coronary intervention was more complicated (death, myocardial infarction; 15 3% vs 4 8%; P=0 02). During the 30-day follow-up period, cardiac risk remained elevated for troponin-positive patients. Conclusions Troponin T rapid testing reliably identified high-risk patients with unstable angina. A higher event rate was observed prior to and particularly in association with the coronary intervention. Coronary revascularization did not abrogate the increased risk of troponin-positive patients during the 30-day follow-up. (Eur Heart J 2000; 21: ) 2000 The European Society of Cardiology Key Words: Unstable angina, troponin T, coronary intervention, prognosis. See page 1117 for the Editorial comment on this article Introduction The large population of patients with unstable angina is heterogeneous, regarding both the severity of the underlying coronary artery disease and the prognosis [1 4]. Therefore, early risk stratification is essential to select the most beneficial and cost-effective approach for the Revision submitted 19 October 1999, and accepted 20 October Presented in part at the XXth Annual Scientific Session of the European Society of Cardiology, Vienna (Austria), August Correspondence: Dr Christopher Heeschen, Stanford University School of Medicine, Division of Cardiovascular Medicine, Stanford, CA, U.S.A X/00/ $35.00/0 individual patient [2]. However, pain is an unreliable indicator for cardiac risk and electrocardiographic criteria are even less specific [1,2,5,6]. Cardiac troponin T as a structure protein with a low molecular weight of 38 kd is a highly sensitive and cardiospecific marker for the detection of myocardial damage [3,7 12]. In patients with unstable angina pectoris, fissure or rupture of the fibrous cap of the atherosclerotic plaque is followed by exposure of plaque content, collagen, and other components of the vascular wall. This results in platelet activation and formation of unstable thrombi [13 15]. Microembolization or severe ischaemia in the dependent myocardium leads to detectable troponin T release in about one third of the patients with unstable angina. Such troponin T-positive patients suffer from the highest subsequent cardiac 2000 The European Society of Cardiology

2 1160 C. Heeschen et al. risk [3,4,8,10,11,16]. However, no distinct therapeutic concept for this high risk subgroup with unstable angina has so far been established [1]. In this prospective study, troponin T was used for risk stratification and decision making in 351 consecutive patients with unstable angina to investigate risk and benefit of the chosen therapeutic strategy according to the troponin status. Methods and patients The study population consisted of 351 consecutive patients (117 females and 234 males, aged 59 9 years, range: 31 to 85 years) admitted via the emergency room of the University Hospital Hamburg (Germany) with unstable angina pectoris (September 1995 to December 1997). Inclusion criterion was angina pectoris at rest within the last 12 h before admission (Braunwald classification III b/c) [17]. The mean duration of anginal pain was h and chest pain was still continuing on admission in 59% of the patients. Exclusion criterion was acute myocardial infarction at the time of arrival, which was defined as an increase in total creatine kinase activity above twice the upper limit of normal (70 U.l 1 man, 80 U.l 1 female) within 24 h of onset of symptoms in the presence or absence of ST-segment elevation. Additionally, patients with recent myocardial infarction, PTCA, or CABG 14 days were excluded due to possible continuous release of troponin T for up to 14 days after such myocardial damage [7]. Study protocol The ethics committee of the Hamburg Medical Board approved the study protocol. After verbal informed consent from each patient was obtained, blood was collected within 15 min of arrival in the emergency room and 4 h later as a supplement to the routine blood draw. All patients had at least two sets of 12-lead ECGs, determination of creatine kinase enzyme activity and troponin T rapid testing. Two trained assistants performed the troponin T test and in all patients the test result was given to the treating physicians. Decision making in the individual patient was left to the physician on duty, following investigations on the influence of the troponin T status on the manner in which the patients were treated and its effect on short-term prognosis. The plasma samples for quantitative troponin T determination were centrifuged at 3000 rpm for 10 min and frozen within 4 h of collection at 80 C. All specimens were thawed only once before testing. The primary end-point of the study was the incidence of major cardiovascular events (cardiac mortality, nonfatal acute myocardial infarction), procedure-related complications and necessity for repeated revascularization during hospitalization, as based on hospital records. Procedure-related complications were defined as mortality, non-fatal acute myocardial infarction or acute necessity for CABG within 24 h of coronary intervention. Acute myocardial infarction was defined as values of creatine kinase enzyme activity more than twice the upper limit of normal in at least two samples, and/or new significant Q waves in two or more continuous leads. The patients were followed for 30 days after discharge to record cardiac events (cardiac mortality, acute myocardial infarction). Electrocardiographic criteria Based on the interpretation of the physician on duty, patients were categorized into the following ECG subgroups: v ST-segment depression 0 2 mv with or without T-wave inversion v T-wave inversion only v Non-diagnostic electrocardiogram bundle-branch block left ventricular hypertrophy paced rhythm v Normal ECG Angiographic evaluation Two independent observers performed analysis of the coronary angiograms. A coronary diameter stenosis 70% was considered as a significant stenosis. Angioplasty was classified successful if the stenosis was reduced to less than 50% of the diameter of the vessel. There were no requirements concerning the technical details of the interventions or antianginal medications. All decisions during the interventions and follow-up period were left to the individual judgement of the treating physicians and those performing the procedures, in order to approximate current therapeutic practice [1]. Analytical techniques For qualitative determination of serum cardiac troponin T in the emergency room, we used a whole blood rapid assay device (Boehringer Mannheim) requiring 150 μl of heparinized whole blood [8,18,19]. Any discernible line within 20 min after application was considered as a positive test result. The rapid test results were controlled quantitatively with a one-step enzyme immunoassay using identical antibodies (ES 300, Boehringer Mannheim) [9,20]. The lower detection limit is 0 04 μg.l 1. The interassay coefficient of variation was 6 7% at 0 2 μg.l 1 and 4 5% at 1 5 μg.l 1 for internal controls. In all samples, creatine kinase MB mass was determined with the Stratus II -Analyser (Dade-Behring) providing a sensitivity of 0 4 μg.l 1. A cut-off level of

3 Risk and benefit of coronary intervention in unstable angina μg.l 1 was used [21]. The interassay precision was 12 5% at 6 μg.l 1 and 6 3% at 35 μg.l 1. Colorimetric determination of total creatine kinase activity at ambient temperatures was performed routinely in the emergency laboratory (Hitachi 717, Boehringer, Mannheim, Germany). Different cut-off values for females (70 U.l 1 ) and males (80 U.l 1 ) according to the manufacturer s specifications were applied. Quantitative determination of the cardiac markers was performed at the cardiac marker research laboratory of the University of Hamburg, blinded to the patients histories and the qualitative troponin T test result. Statistical analysis All results for continuous variables are expressed as means standard deviation. To compare continuous variables between two subgroups the Mann Whitney U test was utilized and comparison of categorical variables was generated by the chi-square test for proportions with appropriate degrees of freedom (McNemar, twosided). P values <0 05 were considered statistically significant. Stepwise logistic regression was performed for possible confoundings by differences in recurrence of anginal pain, ST-T-segment changes and cardiac markers on the in-hospital and 30 day follow-up event rate. All variables in the model were encoded dichotomously and relative risk was expressed in terms of odds ratio with 95% confidence intervals [22,23]. All calculations were done with StatXact-3 (Cytel Software, Cambridge, Massachusetts) or SPSS (Chicago). Results Out of 351 patients with the clinical diagnosis unstable angina, 207 patients (59%) still had chest pain at the time of arrival at the emergency room. The other 116 patients had recovered from symptoms after a severe episode of angina pectoris prior to arrival. All patients were admitted to hospital and 97% of the patients with a positive troponin T test (n=121) and 42% of the patients with a negative troponin T test (n=95) were transferred to the intensive care unit. Troponin T test results A positive rapid test result for troponin T was documented for 75 patients (21%) at the time of arrival. The second blood draw 4 h later provided another positive test results. As 29 patients arrived less than 2 h after onset of pain, the second blood sample did not achieve the demanded minimum time interval of 6 h. For 23 of these 29 patients (79%) a third sample, timed 6 h after arrival, was obtained providing two positive test results. Therefore, troponin T testing performed at least 6 h after onset of symptoms provided 125 positive test results (35 6%). At the time of admission, only 60% of the ultimate 125 troponin T-positive patients were identified. CK MB mass was elevated in 33 patients (9 4%) although CK enzyme activity was within the normal range for all patients enrolled in this study. Baseline characteristics according to the troponin T status are depicted in Table 1. Significant differences were recorded for coronary risk factors and the history of coronary artery disease. Further, ST-segment depression at the time of arrival was 47% in the troponin T-positive patients compared to 24% in the troponin T-negative patients (P=0 001). For 37% of the troponin T-negative patients, no ST-T-segment changes were documented (positive patients 12%; P=0 001) (Table 1). Coronary angiography and revascularization For 250 of the 351 patients with unstable angina (71%) coronary artery disease had already been documented on a previous angiogram. For 167 of these 250 patients (68%), coronary angiography was repeated. Significant stenosis ( 70% of diameter) was documented for 145 patients (58%). PTCA was performed in 112 patients (45%) and surgical revascularization was advised for 16 patients (6 4%). For the other 101 patients with unknown coronary artery disease, coronary angiography was mandatory. For 95 patients (91%), significant stenosis was documented. Culprit lesions were treated by PTCA in 74 (73%) and by CABG in seven patients. No significant coronary artery disease was documented in six patients (6 9%). Coronary intervention according to troponin T status For 119 patients with a positive troponin T test (95%), coronary angiography was performed within an interval of days (Table 2). For eight patients (6 4%), this was related to evolving acute myocardial infarction prior to scheduled angiography (Table 3). For 108 troponin T-positive patients (91%), the angiogram indicated a significant stenosis of at least one vessel. Considering all troponin T-positive patients, revascularization was performed in 58% of the patients by PTCA and in 11% by coronary artery bypass surgery. PTCA was done ad hoc for 63% of the patients. For two of the patients undergoing PTCA, rescue CABG was necessary due to acute refractory vessel occlusion and was unsuccessful in one patient who died perioperatively. A total of 11 patients suffered from a cardiac event within the following 24 h (11 7% periinterventional event rate) which was fatal for two of these patients. In contrast, only 153 of 232 patients with a negative troponin T test (69%) underwent coronary angiography

4 1162 C. Heeschen et al. Table 1 Baseline characteristics of all patients with unstable angina and for the subgroups of patients with a positive and a negative troponin T test result, respectively. Troponin T-positive patients more often had ST-segment depressions, received a more intensive antianginal medication, and had a distinct cardiac risk profile Variables Total Troponin T positive Troponin T negative P value n (36%) 226 (64%) Age Males 234 (67%) 94 (75%) 140 (62%) 0 02 Duration of symptoms Symptomatic on arrival 207 (59%) 79 (63%) 128 (57%) 0 25 Ischaemia on arrival ECG ST-segment depression 113 (32%) 59 (47%) 54 (24%) T-wave inversion 110 (31%) 41 (33%) 69 (31%) 0 68 Confounding factors 29 (8%) 10 (8%) 19 (8%) 0 89 None 99 (28%) 15 (12%) 84 (37%) History of CAD Previous infarction 135 (38%) 31 (25%) 104 (46%) Positive angiogram 249 (71%) 66 (53%) 183 (81%) Prior revascularization 157 (45%) 37 (29%) 120 (53%) Coronary risk factors Hypercholesterolaemia 187 (53%) 81 (65%) 106 (47%) Diabetes mellitus 31 (9%) 15 (12%) 16 (7%) 0 12 Hypertension 191 (54%) 51 (41%) 140 (62%) Current smokers 144 (41%) 60 (48%) 84 (37%) 0 05 Medication on arrival Aspirin/ticlopidin 235 (67%) 86 (69%) 149 (66%) 0 62 Nitrates 158 (45%) 64 (51%) 94 (42%) 0 12 Beta-blockers 220 (63%) 80 (64%) 140 (62%) 0 74 Ca antagonists 176 (50%) 54 (43%) 122 (54%) 0 05 Troponin T level Mean Range Table 2 Angiographic results in patients who underwent angiography during the index hospital stay. Troponin T-positive patients more frequently underwent angiography, indicating a more severe coronary artery disease but only a trend to higher incidence of significant stenosis ( 70% vessel diameter) Variables Total Troponin T positive Troponin T negative P value n 272 (78%) 119 (94%) 153 (68%) No relevant CHD 8 (2 9%) 1 (0 8%) 7 (4 6%) vessel disease 69 (25%) 13 (11%) 56 (37%) < vessel disease 156 (57%) 75 (63%) 81 (53%) vessel disease 35 (13%) 27 (23%) 8 (5%) <0 001 Main vessel 4 (1 5%) 3 (2 5%) 1 (0 6%) 0 21 Significant stenosis ( 1) 240 (88%) 108 (91%) 132 (86%) 0 26 Culprit lesion LAD 149 (62%) 70 (65%) 79 (60%) 0 79 CFX 35 (15%) 14 (13%) 21 (16%) 0 90 RCA 56 (23%) 24 (22%) 32 (24%) 0 72 (P<0 001; troponin T-negative vs -positive patients) after days (P=0 01 vs troponin T-positive patients). For one patient, this was related to developing acute myocardial infarction (0 4% vs 6 4% in troponin T-positive patients; P=0 007). For 132 troponin T-negative patients (86%), the angiogram showed significant stenosis (Table 3). Considering all 232 troponin T-negative patients, revascularization was achieved by angioplasty in 104 patients (46%) and in nine patients (4%) by CABG, resulting in a total revascularization rate of 50% compared to 69% for troponin T-positive patients (P=0 001) (Table 3). The complication rate was significantly lower, with five peri-interventional cardiac events for 104 interventionally treated troponin T-negative patients (4 8%) compared to 11 events in 94 troponin T-positive patients (11 7%; P=0 05);

5 Risk and benefit of coronary intervention in unstable angina 1163 Table 3 Coronary revascularization for all patients with unstable angina and for the subgroups of troponin T-positive and -negative patients, respectively. In troponin T-positive patients coronary revascularization was more frequently attempted both by balloon angioplasty and by bypass surgery. A higher incidence of stent implantation and a higher rate of PTCA-related events was observed Variables Total n=351 Troponin T positive n=125 Troponin T negative n=226 P Cardiac event prior to 9(2 6%) 8 (6 4%) 1 (0 4%) revascularization Angiogram performed 272 (78%) 119 (95%) 153 (69%) <0 001 PTCA 176 (65%) 72 (58%) 104 (46%) stent 109 (62%) 59 (82%) 50/104 (48%) PTCA related events 16 (9 1%) 11 (15 3%) 5 (4 8%) 0 02 CABG 23 (7%) 14 (11%) 9 (4%) 0 01 Revascularization rate 199 (57%) 86 (69%) 113 (50%) TnT (4 h) 96 1% TnT (arrival) 93 3% TnT + (4 h) 82 4% TnT + (arrival) 77 2% day follow-up period Figure 1 Kaplan Meier curve for acute myocardial infarction-free survival in patients with at least one positive troponin T rapid test result as compared to troponin T-negative patients. Major cardiac events (death, acute myocardial infarction) during hospitalization and 30-day follow-up period. Lower risk Higher risk Gender Age > 65 years Diabetes mellitus Hypercholesterolaemia Hypertension History of angina History of MI History of CHD Duration of symptoms > 6 h ST-segment depression T-wave inversion TnT positive CK MB > 5 0 µg.l Figure 2 Odds ratios for cardiac events (death, myocardial infarction) during the 30-day follow-up period. calculated for patients who finally underwent coronary angioplasty. During the 30-day follow-up after hospitalization, four major cardiac events (n=1 death, n=3 acute myocardial infarction) occurred in the study population of which three were documented for troponin T-positive patients (P=0 08). Accordingly, the total event rate for troponin T-positive patients during the entire study period (arrival to 30-day follow-up) was 16 8% compared to 4 9% for troponin T-negative patients (P<0 001) (Fig. 1). Recurrence of angina pectoris after discharge and requiring coronary reintervention was higher for troponin T-positive patients (4 8% vs 2 2%); however, the difference did not reach a level of statistical significance (P=0 12). The combined end-point death, myocardial infarction, and recurrent angina was significantly higher for troponin T-positive patients (7 2% vs. 2 7%; P=0 014). The majority of such events occurred for interventionally managed patients (89%). Multivariate analysis For 223 patients (63%), a positive baseline electrocardiogram was recorded, ST-segment depression was present in 32% and T-wave inversions without STsegment deviations in 31% of the patients. In univariate analysis, ST-segment depression was a significant predictor of cardiac risk (mortality, myocardial infarction) during the 30-day follow-up period (OR 2 05 [95% CI ] P=0 013), whereas evidence of T-wave inversion did not serve as a significant predictor of an adverse outcome (OR 0 72 [95% CI ] P=0 25). When either troponin T status was first entered into a multivariate statistical model, however, neither ST-segment changes, CK MB mass elevation above 5 0 μg.l 1 nor time after onset of symptoms provided independent predictive value for the patients outcome (Fig. 2, Table 4). The only baseline characteristic with significant predictive value was age over 65 years.

6 1164 C. Heeschen et al. Table 4 Odds ratios for cardiac events (mortality, myocardial infarction) during 30-day period Variable OR 95% CI P value Gender Age >65 years Diabetes mellitus Hypercholesterolaemia Hypertension History of angina History of MI History of CHD Duration of symptoms >6 h ST-segment depression T-wave inversion TnT positive <0 001 CK MB >5 0 μg.l Discussion Risk stratification of patients with unstable angina Consistent with that of previous studies [3,4,8,10,11,16,17], our results show that patients with unstable angina and minor myocardial damage evidenced by troponin T elevation are at highest cardiac risk. Although creatine kinase enzyme activity values for all patients remained below the upper limit of normal, troponin T-positive patients had a five-fold higher incidence for cardiac events during hospitalization. In contrast to several recent investigations, however, for this prospective study, the patients troponin T status was taken into account for diagnostic and therapeutic decision making during hospitalization. Management of the individual patient was left to the physician on duty, who investigated the influence of the troponin T status on the manner in which the patients were treated and its effect on short-term prognosis. Baseline characteristics for our patients with unstable angina showed no significant differences between subgroups stratified according to the troponin T status. During subsequent hospitalization, however, more episodes of recurrent angina with or without ST-T-segment changes were documented for troponin T-positive patients. This was observed despite more intensive medical treatment, including intravenous application of heparin and nitrates for the majority of troponin T-positive patients (Table 5). Further, for most of the troponin T-positive patients, an invasive diagnostic strategy was chosen. They were catheterized earlier and more frequently than patients with a negative test result. Accordingly, troponin T-positive patients were managed more aggressively, which at least in part might have been related to the knowledge of the troponin T status. All treating physicians were informed about the prognostic impact of a positive troponin bedside test. For 6 5% of the troponin T-positive patients, however, an antithrombotic was not sufficient and several patients suffered myocardial infarction or death before they were sent to the catheterization laboratory. The subsequent angiogram indicated more severe coronary artery disease for troponin T-positive patients with a higher incidence of significant stenoses ( 70% vessel diameter). Consequently, these patients had a higher rate of coronary revascularization. During the following coronary intervention, troponin T-positive patients were at particularly high risk and significantly more cardiac complications occurred both during the intervention and within the first 24 h after completion of the procedure (15 3% vs 4 8%; P<0 001). Further, this difference in cardiac risk also persisted during the 30-day follow-up period and both incidence of major cardiac events (death, myocardial infarction) and recurrent episodes of angina pectoris requiring coronary reintervention were more frequent for troponin T-positive patients. Interestingly, the majority of such events documented for troponin T-positive patients occurred in interventionally managed patients. Therapeutic options for high-risk patients with unstable angina Low molecular weight heparin For troponin-positive patients, a significantly increased risk of complications, both related and unrelated to coronary interventions, indicates the necessity for new therapeutic approaches in such high-risk patients. For the prolonged treatment of troponin T-positive patients with the low molecular weight heparin, dalteparin, an increased benefit of treatment was documented in the FRISC trial [24]. However, it should be noted that the rate of coronary interventions was low for this study population with 13 8% during the 5-week treatment period. A direct comparison of unfractionated heparin and dalteparin during a 6-day treatment period for patients with unstable angina did not provide significant outcome differences [25]. In contrast, others reported a significant reduction in primary end-points (death, acute myocardial infarction and recurrent angina) for the 2- to 8-day treatment period with enoxaparin compared to unfractionated heparin; this difference was also seen at the 30-day follow-up [26]. Therefore, the results for low molecular weight heparin in acute coronary syndrome remain controversial. Glycoprotein IIb/IIIa receptor antagonists Angioscopic studies indicated that thrombus in patients with unstable angina is a platelet-rich thrombus formation, in contrast to the fibrin thrombus observed in patients suffering from acute myocardial infarction [27]. Increasing evidence supports the hypothesis that troponin T release in patients with unstable angina can be interpreted as thromboembolic myocardial injury originating from friable thrombus formation at ruptured or eroded plaques [28,29]. Since aspirin and/or ticlopidin alone do not completely inhibit platelet activation, a

7 Risk and benefit of coronary intervention in unstable angina 1165 Table 5 Course of hospitalization for all patients with unstable angina and for the subgroups of patients with a positive and a negative troponin T test result, respectively. Clinical symptoms in troponin T-positive patients were more often refractory to medical treatment. During hospitalization and the 30 day follow-up period the incidence for death and non-fatal myocardial infarction was still higher in troponin T-positive patients Variables Total Troponin T positive Troponin T negative P value Medication during hospitalization ASA/ticlopidin 340 (97%) 123 (98%) 217 (96%) 0 29 Heparin i.v. 313 (89%) 121 (97%) 192 (85%) Nitrates i.v. 226 (64%) 79 (63%) 104 (46%) Beta-blockers 249 (71%) 93 (74%) 156 (69%) 0 38 Ca antagonists 166 (47%) 53 (42%) 113 (50%) 0 23 Refractory angina 197 (56%) 98 (78%) 99 (44%) ST-T-segment changes 112 (32%) 55 (44%) 57 (25%) during hospitalization In-hospital event rate 27 (7 7%) 19 (15 2%) 8 (3 5%) <0 001 Event rate after discharge 4 (1 1%) 3 (2 4%) 1 (0 4%) 0 08 Total event rate 31 (8 8%) 22 (17 6%) 9 (3 9%) <0 001 more potent blockade of platelet aggregation appears as a reasonable approach. For glycoprotein IIb/IIIa antagonists, such as abciximab, a significant improvement in the clinical effects of aspirin and unfractionated heparin has been demonstrated in association with coronary interventions [30 32]. Further, in the CAPTURE trial, enrolling patients with refractory unstable angina, abciximab was shown to deliver a significant reduction in the primary end-points death and myocardial infarction both prior to and in association with coronary intervention [32]. Interestingly, this benefit of treatment was achieved in patients with elevated baseline troponin T concentrations [33]. Primary end-points were reduced by 82% during the first 72 h after randomization (OR 0 18; P<0 001). In contrast, troponin T-negative patients were at low cardiac risk prior to, and in association with, coronary intervention. No significant benefit of treatment with abciximab was documented for such low-risk patients (OR 1 07; P=0 37). With respect to the high incidence of myocardial infarctions, both prior to and during coronary interventions, for such troponin-positive patients enrolled in our study and discussed here, this advanced therapeutic approach, with GP IIb/IIIa receptor antagonists for a selected cohort of high-risk patients, seems promising. Further evidence supporting this concept has recently been provided from the troponin subgroup of the PRISM trial, which demonstrated the outstanding therapeutic efficacy of the GP IIb/IIIa receptor antagonist tirofiban. Benefit of treatment was observed in regard to both reduction of death and myocardial infarction during the 30-day follow-up period [34]. However, this new therapeutic concept, with coupling of new diagnostic and therapeutic tools, still has to be verified in future prospective studies which are currently underway. In conclusion, standard antithrombotic treatment is not sufficient for highly symptomatic and endangered troponin T-positive patients with unstable angina. No decrease in cardiac risk was observed, even when treating physicians are aware of the troponin T status. Optimal treatment for such patients, thus, still needs further investigation. Given limited budgets, with increasing necessity to allocate expensive therapeutic options to patients who are at highest cardiac risk and/or provide highest benefit from treatment, the indication for new therapeutic approaches, including GP IIb/IIIa receptor antagonists, should be guided by troponin determination. References [1] Braunwald E, Jones RH, Mark DB et al. Diagnosing and managing unstable angina. Agency for Health Care Policy and Research. Circulation 1994; 90: [2] Goldman L, Cook F, Fohnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to emergency departments with acute chest pain. 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