Invasive Versus Conservative Treatment in Unstable Coronary Syndromes - ICTUS

Contribution To Literature:

The ICTUS trial failed to show that a routine invasive strategy in non-ST elevation ACS reduces death or MI.


The goal of the ICTUS trial was to evaluate the use of an early invasive strategy compared with a more conservative, selective invasive strategy in troponin-positive patients with non-ST elevation myocardial infarction (MI) acute coronary syndromes (ACS).

Study Design

Patients Enrolled: 1,200
Mean Follow Up: 3 years, 10 years
Median Patient Age: 62 years
Female: 26%

Patient Populations:

Anginal symptoms at rest within 24 hours, troponin T ≥0.03 mcg/L, and history of coronary artery disease or ischemic changes on ECG


Q-wave MI or ST elevation MI within 48 hours or acute ST elevation MI

Primary Endpoints:

Death, MI, or rehospitalization for ACS at 1 year

Drug/Procedures Used:

Patients presenting with unstable angina who were troponin-positive were randomized to an early invasive strategy (n = 604) or a selective invasive strategy (n = 596). The early invasive strategy included coronary angiography within 24-48 hours and percutaneous coronary intervention (PCI) within 48 hours or coronary artery bypass grafting (CABG) as soon as possible. The selective invasive strategy included medical stabilization with angiography and revascularization only in case of refractory angina or ischemia on predischarge exercise testing. The trial was conducted at 12 centers in The Netherlands.

Concomitant Medications:

Aspirin, enoxaparin, beta-blockers, nitrates, clopidogrel, high-dose statin therapy, and abciximab at the time of PCI

Principal Findings:

The median troponin T was 0.3 mcg/L, and 62% of patients had ischemic changes. Angiography by hospital discharge was performed in 98% in the early invasive group and 53% in the selective invasive group. Revascularization was performed by hospital discharge in 76% of patients in the early invasive group and 40% of patients in the selective invasive group, with a shorter median time to revascularization in the early invasive group (19 hours vs. 142 hours).

There was no difference by treatment group in the primary composite endpoint of death, MI, or rehospitalization for ACS at 1 year (22.7% in early invasive vs. 21.2% in selective invasive, relative risk [RR] 1.07, p = 0.33). The lack of difference in the primary endpoint is driven by divergent results for the endpoint of MI (15.0% in early invasive vs. 10.0% in selective invasive, RR 1.50, p = 0.005) and rehospitalization for ACS (7.4% in early invasive vs. 10.9% in selective invasive, RR 0.68, p = 0.04). There was no difference in mortality at 1 year (2.5% each, p = 0.97).

The criteria for MI was >1x the upper limit of normal, a less stringent definition than early trials such as TACTICS-TIMI 18 and FRISC-2. When applying the TACTICS-TIMI 18 definition for MI to the present trial, the rate of MI was 8.5% in the early invasive group and 5.9% in the selective invasive group (p = 0.07). Likewise, when applying the FRISC-2 definition of MI, the rate of MI was 12.1% and 7.8%, respectively (p = 0.008).

At 3-year follow-up, the composite of death, MI, or rehospitalization for ACS did not significantly differ for the invasive group compared with the conservative group (30.0% vs. 26.0%, HR 1.20, p = 0.10). There was also no difference in all-cause mortality (7.9% vs. 7.7%, RR 1.11, p = 0.63) or cardiac death (5.0% vs. 4.5%, p = 0.92).

At 10-year follow-up, the composite of death or spontaneous MI did not significantly differ for the invasive group compared with the conservative group (33.8% vs. 29.0%, HR 1.12, p = 0.11). There was also no difference in all-cause mortality (26.7% vs. 23.7%, RR 1.14, p = 0.25) or cardiac death (17.6% vs. 15.2%, RR 1.15, p = 0.34).


Among troponin-positive patients with a non-ST elevation ACS, treatment with an early invasive strategy was not associated with a difference in the primary endpoint compared with a selective invasive strategy. MI and rehospitalization for ACS occurred at a higher frequency in the early invasive group. The rate of MI in the present trial was notably higher than other similar trials, likely a reflection of periprocedural MI given the nonstringent definition of MI of creatine kinase-MB >1 times the upper limit of normal. At 10-year follow-up, there was no reduction in death or spontaneous MI from early invasive therapy compared with conservative therapy.

The primary endpoint and MI data in the present trial are not in line with the TACTICS-TIMI 18 and FRISC II trials, which showed benefit of an early invasive strategy over a conservative strategy in a similar patient population. In addition to the differences noted in the MI definition between the trials, a larger percentage of patients in the more conservative strategy in the present trial underwent early revascularization (40%) than in the TACTICS-TIMI 18 (36%) or FRISC-2 (9%) trials. Unlike the RITA-3 and FRISC II trials, a late benefit with the invasive strategy was not observed at 3-year follow-up.


Hoedemaker NP, Damman P, Woudstra P, et al. Early Invasive Versus Selective Strategy for Non–ST-Segment Elevation Acute Coronary Syndrome: ICTUS Trial. J Am Coll Cardiol 2017;69:1883-93.

Presented by Dr. RJ de Winter at the European Society of Cardiology Congress, Rome, Italy, August 29, 2016.

De Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095-104.

De Winter RJ. ICTUS: Invasive versus Conservative Treatment in Unstable Coronary Syndromes. Paper presented at the European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.

Long-term follow-up data presented by RJ de Winter, European Society of Cardiology Scientific Congress, September 2006.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Risk, Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Creatine Kinase, Coronary Angiography, Troponin T, Electrocardiography, Coronary Artery Bypass, Percutaneous Coronary Intervention, ESC Congress

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