Friday, July 20, 2007


Three year follow-up from the ICTUS trial: Early intervention or selective-based treatment for coronary heart disease?

Christopher CannonTIMI Study Group, Boston, MA, USA19 June 2007

Globally, coronary artery disease (CAD) is the leading cause of mortality, with non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) being the most common manifestations of this condition.

There has been much debate over the past decade regarding the optimal management of patients with CAD.

Should we provide routine early invasive strategies, or do we need to adopt a more “conservative” approach based on selective intervention focused towards high-risk patients?

Cardiac catheterization and revascularization: The two main approaches
There are two general approaches to the use of cardiac catheterization and revascularization in UA/NSTEMI.

The “early invasive” strategy involves routine early cardiac catheterization and revascularization with percutaneous coronary intervention (PCI), or bypass surgery depending on the coronary anatomy.

The “conservative” strategy involves providing initial medical management, with catheterization and revascularization only for recurrent ischemia either at rest or on a non-invasive stress test.

The ACC/AHA guidelines were updated in 2002, and were based on the results of the FRagmin and Fast Revascularization during InStability in coronary artery disease (FRISC II) and Treat Angina with aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy - Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trials, both of which compared early invasive strategies with the conservative approach.

The results of these trials suggested that patients who received early invasive therapy benefited more than those who underwent conservative treatment.

However, to date, 10 randomized trials have studied the relative merits of an invasive versus a conservative strategy. These include the FRISC-II, RITA-3, and TACTICS. These trials yielded varying results.

Of note, the other recent long-term follow-up data available from the RITA-3 trial demonstrated a benefit of a significantly lower cardiovascular mortality rate in the early invasive arm which was observed over five years. [1] A meta-analysis of the contemporary trial has confirmed an overall significant reduction in death, MI or rehospitalization during follow-up was observed. [2]

The most recent trial, Invasive Treatment Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), examined an invasive versus conservative approach in 1200 patients. All patients received aspirin, enoxaparin, abciximab for PCI and intensive statin therapy. At one, year there was no significant difference in the rate of the primary endpoint, death, MI, or rehospitalization for angina. [3]

During the index hospitalization, there was a higher rate of MI in the invasive arm, although this trial used a definition of MI that included any elevation of any biomarker following PCI, and thus had a much higher peri-procedural MI rate compared with prior trials.

Throughout the three year follow-up period, the higher overall rate of MI (again using their definition of MI) persisted, with rates of 18 versus 12 (p=0). No difference in mortality was seen. [4]

How do we incorporate this new information? Based on multiple randomized trials, an early invasive strategy remains the recommended approach to higher risk patients with UA/NSTEMI who have either ST-segment changes, positive troponin, or other other high-risk indicators, such as recurrent ischemia, evidence of congestive heart failure. [5]


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.

Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol 2006; 48:1319-25.

Hirsch A, Windhausen F, Tijssen JG, Verheugt FW, Cornel JH, de Winter RJ. Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. Lancet 2007; 369:827-35.

Fox KAA, Poole-Wilson P, Clayton TC, et al. 5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005; 366:914-920.

Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: Summary Article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002; 106:1893-900.

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