Invasive Versus Conservative Treatment In Unstable Coronary Syndromes Research Articles

Early Invasive Versus Selective Strategy for Non–ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial

BackgroundThe ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years. ObjectivesThe aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T. MethodsThe ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization. ResultsTen-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001). ConclusionsIn patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients.

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

BackgroundNo 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). MethodsThis 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 <1200ng/L, 1200–1800ng/L and >1800ng/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) ResultsCompared to GDF-15<1200ng/L, a GDF-15>1800ng/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. ConclusionIn 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-up.

Timing of Angiography With a Routine Invasive Strategy and Long-Term Outcomes in Non–ST-Segment Elevation Acute Coronary Syndrome: A Collaborative Analysis of Individual Patient Data From the FRISC II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or

This study sought to investigate long-term outcomes after early or delayed angiography in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS) undergoing a routine invasive management. The optimal timing of angiography in patients with nSTE-ACS is currently a topic for debate. Long-term follow-up after early (within 2 days) angiography versus delayed (within 3 to 5 days) angiography was investigated in the FRISC-II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) (FIR) nSTE-ACS patient-pooled database. The main outcome was cardiovascular death or myocardial infarction up to 5-year follow-up. Hazard ratios (HR) were calculated with Cox regression models. Adjustments were made for the FIR risk score, study, and the propensity of receiving early angiography using inverse probability weighting. Of 2,721 patients originally randomized to the routine invasive arm, consisting of routine angiography and subsequent revascularization if suitable, 975 underwent early angiography and 1,141 delayed angiography. No difference was observed in 5-year cardiovascular death or myocardial infarction in unadjusted (HR: 1.06, 95% confidence interval [CI]: 0.79 to 1.42, p=0.61) and adjusted (HR: 0.93, 95% CI: 0.75 to 1.16, p=0.54) Cox regression models. In the FIR database of patients presenting with nSTE-ACS, the timing of angiography was not related to long-term cardiovascular mortality or myocardial infarction. (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes [ICTUS]; ISRCTN82153174. Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction [the Third Randomised Intervention Treatment of Angina Trials (RITA-3)]; ISRCTN07752711).

Long-Term Cardiovascular Mortality After Procedure-Related or Spontaneous Myocardial Infarction in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome

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 &lt;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. Clinical Trial Registration— URL: http://www.controlled-trials.com/ISRCTN82153174 (ICTUS); http://www.controlled-trials.com/ISRCTN07752711 (RITA-3).

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 Outcome of a Routine Versus Selective Invasive Strategy in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome: A Meta-Analysis of Individual Patient Data

This study was designed to determine: 1) whether a routine invasive (RI) strategy reduces the long-term frequency of cardiovascular death or nonfatal myocardial infarction (MI) using a meta-analysis of individual patient data from all randomized studies with 5-year outcomes; and 2) whether the results are influenced by baseline risk. Pooled analyses of randomized trials show early benefit of routine intervention, but long-term results are inconsistent. The differences may reflect differing trial design, adjunctive therapies, and/or limited power. This meta-analysis (n = 5,467 patients) is designed to determine whether outcomes are improved despite trial differences. Individual patient data, with 5-year outcomes, were obtained from FRISC-II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Trial of a Conservative Treatment Strategy Versus an Interventional Treatment Strategy in Patients with Unstable Angina) trials for a collaborative meta-analysis. A Cox regression analysis was used for a multivariable risk model, and a simplified integer model was derived. Over 5 years, 14.7% (389 of 2,721) of patients randomized to an RI strategy experienced cardiovascular death or nonfatal MI versus 17.9% (475 of 2,746) in the selective invasive (SI) strategy (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71 to 0.93; p = 0.002). The most marked treatment effect was on MI (10.0% RI strategy vs. 12.9% SI strategy), and there were consistent trends for cardiovascular deaths (HR: 0.83, 95% CI: 0.68 to 1.01; p = 0.068) and all deaths (HR: 0.90, 95% CI: 0.77 to 1.05). There were 2.0% to 3.8% absolute reductions in cardiovascular death or MI in the low- and intermediate-risk groups and an 11.1% absolute risk reduction in highest-risk patients. An RI strategy reduces long-term rates of cardiovascular death or MI and the largest absolute effect in seen in higher-risk patients.

Invasive treatment of ACS: early or later on?

In a recent online publication in the Journal of the American College of Cardiology, 30 December 2009, Damman from the group of de Winter (AMC, Amsterdam) published the five-year clinical outcome in the Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) The ICTUS trial was supported by the Interuniversity Cardiology Institute of the Netherlands (ICIN), the Working Group on Cardiovascular Research of the Netherlands (WCN), and educational grants form Eli Lilly, Sanofi/Synthelabo, Sanofi-Aventis, Medtronic, and Roche Diagnostics.

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-Segment Elevation Acute Coronary Syndrome

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. 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. 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. 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. 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).

Should We Manage Patients With Non-ST Segment Elevation Myocardial Infarction With Renal Failure With an Invasive Strategy?

Szummer and colleagues raise an important question: Should we manage patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) with an early invasive strategy?1 It makes good sense to do this. We know that patients with renal dysfunction are at high risk,2 and the American College of Cardiology/American Heart Association and European Society of Cardiology guidelines both recommend an early invasive strategy for patients with unstable angina/NSTEMI who are high risk.3,4 Neither guideline, however, specifically notes that renal dysfunction should be a specific indication for an invasive strategy. Article see p 851 The investigators analyzed 23262 consecutive NSTEMI patients who had been included in a nationwide coronary care unit registry between 2003 and 2006 called the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).1 Patients were divided into medically or invasively treated if revascularized within 14 days of admission. They found that for patients with worse renal function, the rate of performing revascularization was lower. This “risk paradox” has been seen in other registries, in which higher-risk patients are actually managed less intensively.5 They also found that 1-year mortality was substantially higher for those on dialysis or having an estimated glomerular filtration rate (GFR) <15 mL/min (≈55%) versus ≈40% for those with estimated GFR 15 to 29 mL/min and <5% for those with normal renal function. Thus, estimated GFR is clearly an important risk marker. They went on to compare mortality between medically managed patients and those who had revascularization and found overall a difference in mortality, with 36% lower adjusted mortality among those who had revascularization. They then split out the group by baseline renal function and found a lower mortality for those who had been revascularized versus not in most groups but not …

ST-segment deviation on the admission electrocardiogram, treatment strategy, and outcome in non–ST-elevation acute coronary syndromes: A substudy of the Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) Trial

Background We assessed the prognostic significance of the presence of cumulative ( ∑) ST-segment deviation on the admission electrocardiogram (ECG) in patients with non–ST-elevation acute coronary syndrome and an elevated troponin T randomized to a selective invasive (SI) or an early invasive treatment strategy. Methods A 12-lead ECG obtained at admission was available for analysis from 1163 patients. The presence and magnitude of ST-segment deviation was measured in each lead, and absolute ST-segment deviation was summed. The effect of treatment strategy was assessed for patients with or without ∑ ST-segment deviation of at least 1 mm. Results The incidence of death or myocardial infarction (MI) by 1 year in patients with ∑ ST-segment deviation of at least 1 mm was 18.0% compared with 11.1% in patients with ∑ ST-segment deviation of less than 1 mm ( P = .001). Among patients with ∑ ST-segment deviation of at least 1 mm, the incidence of death or MI was 21.9% in the early invasive group compared with 14.2% in SI group ( P < .01). However, we observed a significantly higher rate of MI after hospital discharge among patients with ∑ ST-segment deviation of at least 1 mm randomized to SI who did not undergo angiography compared with patients who underwent angiography before discharge (10.9% vs 2.4%, P = .003). In a forward logistic regression analysis, the presence of ST-segment deviation was an independent predictor for failure of medical therapy (coronary angiography within 30 days after randomization in the SI group) (odds ratio, 1.56; 95% confidence interval, 1.12-2.18; P = .009). Conclusion Patients with non–ST-elevation acute coronary syndrome and an elevated troponin T and ∑ ST-segment deviation of at least 1 mm are at increased risk of death or MI, more often fail on medical therapy, and more often experience a spontaneous MI after discharge when angiography was not performed during initial hospitalization.

PO1-23 ACAT2 AND HUMAN HEPATIC CHOLESTEROL METABOLISM: IDENTIFICATION OF IMPORTANT GENDER-RELATED DIFFERENCES

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.

N-terminal pro–brain natriuretic peptide for additional risk stratification in patients with non–ST-elevation acute coronary syndrome and an elevated troponin T: An Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy. Baseline samples for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT randomized to an early or a selective invasive strategy. Patients were followed-up for the occurrence of death, myocardial infarction (MI), and rehospitalization for angina. We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease. Mortality by 1 year was 7.3% in the highest quartile (> or = 1170 ng/L for men, > or = 2150 ng/L for women) compared with 1.1% of patients in the lower 3 quartiles (P < .0001). N-terminal pro-brain natriuretic peptide (highest quartile vs lower 3 quartiles) was a strong independent predictor of mortality (hazard ratio 5.0, 95% CI 2.1-11.6, P = .0002). However, NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year. Furthermore, we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level. We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy.