Early Invasive Strategy vs Selective Invasive Strategy: Long-Term Follow-Up Data from ICTUS

September 21, 2017

Key Takeaways

  • According to an analysis of the ICTUS trial, there is no significant long-term mortality or spontaneous myocardial (MI) benefit among selective vs early invasive strategies for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS).
  • These findings contradict earlier studies, and issues with the study’s long-term follow-up may reduce the significance of these findings.

The Invasive vs Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial compared the use of an early invasive strategy vs an ischemia-guided strategy for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). An ischemia-guided approach, also referred to as a selective invasive strategy, involves the use of diagnostic cardiac catheterization and revascularization following objective evidence of myocardial ischemia. An early invasive approach, however, involves early routine coronary angiography followed by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

In a report by Hoedemaker et al,1 the authors examined the 10-year outcomes of the ICTUS trial to determine the long-term rate of all-cause mortality, cardiovascular death, and spontaneous and procedure-related myocardial infarction (MI). The primary outcome was the composite of all-cause mortality and spontaneous MI.

Authors evaluated 1200 patients with NSTE-ACS with an elevated cardiac troponin T (≥0.03 g/l). Randomization into either an early or selective invasive approach was performed within 24 hours after symptoms onset.

Patients randomized to the selective invasive strategy in the ICTUS trial received antithrombotic and antianginal treatment and coronary angiography in the setting of inducible ischemia or refractory angina during a pre-discharge ischemia detection assessment. Those assigned to an early invasive approach also received antithrombotic and antianginal therapy and underwent coronary angiography within 24 to 48 hours following randomization. Continued optimized pharmacological therapy or revascularization was used following angiography.

An approximately equal number of the study’s patient population was randomized to either selective invasive or early invasive strategy (n = 596 and n = 604, respectively).

At 10-year follow-up, vital status was known for 96% of patients. The composite outcome of mortality or spontaneous MI was 29.0% and 33.8% for the selective invasive and early invasive group, respectively. There was a higher rate of procedure-related MI among patients receiving early invasive vs selective invasive strategies (6.5% vs 2.4%, respectively).

Due to periprocedural MI, there was an increased incidence of long-term mortality and MI in the early invasive group. Per the results of this analysis, researchers concluded there was no significant long-term mortality or spontaneous MI benefit among selective vs early invasive strategies for NSTE-ACS.

These findings contradict earlier studies, including a 2010 meta-analysis by Fox KA et al. This analysis pooled together patient data from the RITA-3, FRISC II, and ICTUS trials.3 This meta-analysis showed a reduction of cardiovascular death or MI at 5 years; however, significant differences in mortality dissipated at 10 and 15 years for all studies.4 The FRISC-II and RITA-3 trials, however, featured temporal differences in regard to patient enrollment as well as differences in clinical practice and intensity of revascularization.

In an accompanying editorial, Bavry explains that earlier benefit from invasive therapy may not be sustained to 10 years due to issues associated with long-term follow-up.5 According to    Bavry, “Many patients initially selected for an ischemia-guided approach will ultimately have catheterization performed.” He adds, “From randomized trial data, approximately one-third to one-half of patients in the control arm underwent revascularization after the index hospitalization. Taken to an extreme, mortality will be 100% in both treatment groups if follow-up is long enough.”

ICTUS concluded that early invasive therapy correlates with a similar incidence of mortality or spontaneous MI as selective invasive therapy. In order to evaluate the clinical impact of early vs selective treatment strategies and “to refine the lowest risk patients who are appropriate for conservative therapy,” according to Bavry, randomized controlled clinical trials with long-term follow-up are necessary.


  1. Hoedemaker NP, Damman P, Woudstra P, et al. Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial. J Am Coll Cardiol. 2017;69(15):1883-1893.
  2. Monroe VS, Kerensky RA, Rivera E, Smith KM, Pepine CJ. Pharmacologic plaque passivation for the reduction of recurrent cardiac events in acute coronary syndromes. J Am Coll Cardiol 2003;41: 23S–30S.
  3. Fox KA, Clayton TC, Damman P, et al. 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. J Am Coll Cardiol. 2010;55(22):2435-2445.
  4. Henderson RA, Jarvis C, Clayton T, Pocock SJ, Fox KA. 10-Year Mortality Outcome of a Routine Invasive Strategy Versus a Selective Invasive Strategy in Non-ST-Segment Elevation Acute Coronary Syndrome: The British Heart Foundation RITA-3 Randomized Trial. J Am Coll Cardiol. 2015;66(5):511-520.
  5. Bavry AA. Non–ST-Segment Elevation Acute Coronary Syndromes: Lessons Learned Over the Last Decade. 2017;69(15).


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