5-Year Clinical Outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) Trial A Randomized Comparison of an Early Invasive Versus Selective Invasive Management in Patients With Non-ST-Elevation Acute Coronary Syndrome

OBJECTIVES: We present the 5-year clinical outcomes according to treatment strategy with additional risk stratification of the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial. BACKGROUND: Long-term outcomes may be relevant to decide treatment strategy for patients presenting with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and elevated troponin T. METHODS: We randomly assigned 1,200 patients to an early invasive or selective invasive strategy. The outcomes were the composite of death or myocardial infarction (MI) and its individual components. Risk stratification was performed with the FRISC (Fast Revascularization in InStability in Coronary artery disease) risk score. RESULTS: At 5-year follow-up, revascularization rates were 81% in the early invasive and 60% in the selective invasive group. Cumulative death or MI rates were 22.3% and 18.1%, respectively (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.00 to 1.66, p = 0.053). No difference was observed in mortality (HR: 1.13, 95% CI: 0.80 to 1.60, p = 0.49) or MI (HR: 1.24, 95% CI: 0.90 to 1.70, p = 0.20). After risk stratification, no benefit of an early invasive strategy was observed in reducing death or spontaneous MI in any of the risk groups. CONCLUSIONS: In patients presenting with NSTE-ACS and elevated troponin T, we could not demonstrate a long-term benefit of an early invasive strategy in reducing death or MI. (Invasive versus Conservative Treatment in Unstable coronary Syndromes [ICTUS]; ISRCTN82153174

Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes: a collaborative analysis of individual data from the FRISC II - ICTUS - RITA-3 (FIR) trials.

OBJECTIVE: To perform a patient-pooled analysis of a routine invasive versus a selective invasive strategy in elderly patients with non-ST segment elevation acute coronary syndrome. METHODS: A meta-analysis was performed of patient-pooled data from the FRISC II-ICTUS-RITA-3 (FIR) studies. (Un)adjusted HRs were calculated by Cox regression, with adjustments for variables associated with age and outcomes. The main outcome was 5-year cardiovascular death or myocardial infarction (MI) following routine invasive versus selective invasive management. RESULTS: Regarding the 5-year composite of cardiovascular death or MI, the routine invasive strategy was associated with a lower hazard in patients aged 65-74 years (HR 0.72, 95% CI 0.58 to 0.90) and those aged ≥75 years (HR 0.71, 95% CI 0.55 to 0.91), but not in those aged <65 years (HR 1.11, 95% CI 0.90 to 1.38), p=0.001 for interaction between treatment strategy and age. The interaction was driven by an excess of early MIs in patients <65 years of age; there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p=0.009 for interaction). After adjustment for other clinical risk factors the HRs remained similar. CONCLUSION: The current analysis of the FIR dataset shows that the long-term benefit of the routine invasive strategy over the selective invasive strategy is attenuated in younger patients aged <65 years and in women by the increased risk of early events which seem to have no consequences for long-term cardiovascular mortality. No other clinical risk factors were able to identify patients with differential responses to a routine invasive strategy. Trial registration http://www.controlled-trials.com/ISRCTN82153174 (ICTUS), http://www.controlled-trials.com/ISRCTN07752711 (RITA-3)

Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). This is a subanalysis from the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial, including troponin positive NSTE-ACS patients. The main outcome for the current analysis was 5-year death or spontaneous MI. GDF-15 samples were available in 1151 patients. The prognostic value of GDF-15, categorized into 1800 ng/L, was assessed in unadjusted and adjusted Cox regression models. Adjustments were made for identified univariable risk factors. The additional discriminative and reclassification value of GDF-15 beyond the independent risk factors was assessed by the category-free net reclassification improvement (1/2 NRI(>0)) and the integrated discrimination improvement (IDI) RESULTS: Compared to GDF-15 1800 ng/L was associated with an increased hazard ratio for death or spontaneous MI, mainly driven by mortality. GDF-15 levels were predictive after adjustments for other identified predictors. Additional discriminative value was shown with the IDI, not with the NRI. In patients presenting with NSTE-ACS and elevated troponin T, GDF-15 provides prognostic information in addition to identified predictors for mortality and spontaneous MI and can be used to identify patients at high risk during long-term follow-u

Additional diagnostic value of CMR to the European Society of Cardiology (ESC) position statement criteria in a large clinical population of patients with suspected myocarditis

Aims: To determine the diagnostic yield of tissue characterization by cardiovascular magnetic resonance (CMR) in a large clinical population of patients with suspected acute myocarditis (AM) and to establish its diagnostic value within the 2013 European Society of Cardiology position statement criteria (ESC-PSC) for clinically suspected myocarditis. Methods and results: In this retrospective study, CMR examinations of 303 hospitalized patients referred for work-up of suspected AM in two tertiary referral centres were analysed. CMR was performed at median 7 days (interquartile range 4-20 days) after clinical presentation and included cine imaging, T2-weighted imaging, and late gadolinium enhancement. CMR images were evaluated to assign each patient to a diagnosis. By using non-CMR criteria only, the 2013 ESC-PSC were positive for suspected myocarditis in 151 patients and negative in 30. In the remaining 122 patients, there was insufficient information available for ESC-PSC assessment, mostly due to lack of coronary angiography (CAG) before the CMR examination (n = 116, 95%). There were no in-hospital deaths. CMR provided a diagnosis in 158 patients (52%), including myocarditis in 104 (34%), myocardial infarction in 44 (15%), and other pathology in 10 patients (3%). Non-urgent CAG (>24 h after presentation) was performed before the CMR examination in 85 patients, of which 20 (24%) were done in patients with subsequently confirmed AM, which could potentially have been avoided if CMR was performed first. ESC-PSC was correct in diagnosing AM before the CMR in 50 of the 151 patients (33%) and was correct in ruling out AM in all the 30 patients (100%). However, ESC-PSC provided an incorrect diagnosis of AM in 27 of the 151 patients (18%), which was corrected by CMR through the identification of new cardiac disease that could explain the clinical syndrome. Patients with insufficient ESC-PSC information had a relatively low pre-test probability of coronary artery disease. In this group, CMR confirmed the diagnosis of AM in a relatively high percentage (44%) but still revealed myocardial infarction in 8% of them. Conclusion: Tissue characterization by CMR provided a good diagnostic yield in this large clinical population of patients with suspected AM. CMR provided incremental diagnostic value to the ESC-PSC by ruling out the diagnosis of AM on one hand and by potentially sparing AM patients from CAG on the other

Usefulness of the admission electrocardiogram to predict long-term outcomes after non-ST-elevation acute coronary syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials).

The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data

Long-term cardiovascular mortality after procedure-related or spontaneous myocardial infarction in patients with non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II, ICTUS, and RITA-3 trials (FIR).

BACKGROUND: The present study was designed to investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome. METHODS AND RESULTS: Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient pooled data set of the FRISC-II (Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Intervention Trial of Unstable Angina 3) non-ST-elevation acute coronary syndrome trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated by the Kaplan-Meier method; hazard ratios were calculated with time-dependent Cox proportional hazards models. Adjustments were made for the variables associated with long-term outcomes. Among the 5467 patients, 212 experienced a procedure-related MI within 6 months after enrollment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who had a procedure-related MI, comparable to that for patients without a procedure-related MI (hazard ratio 0.66; 95% confidence interval, 0.36-1.20, P=0.17). In patients who had a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2%, higher than for patients without a spontaneous MI (hazard ratio 4.52; 95% confidence interval, 3.37-6.06, P<0.001). These hazard ratios did not change materially after risk adjustments. CONCLUSIONS: Five-year follow-up of patients with non-ST-elevation acute coronary syndrome from the 3 trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast, there was a substantial increase in long-term mortality after a spontaneous MI