ACS without ST-Segment Elevation: How Fast to the Cath Lab?

Abstract & Commentary

By Richard Harrigan, MD, FAAEM Dr. Harrigan is Associate Professor of Emergency Medicine, Temple University School of Medicine, Philadelphia Dr. Harrigan reports no financial relationships with companies with ties to this field of study.

Source: DeWinter RJ, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095-1104.

It is well-established that patients with acute coronary syndrome (ACS) with ST-segment elevation (STE) on the electrocardiogram (ECG) benefit from early coronary revascularization—preferably by percutaneous coronary intervention (PCI), but also via fibrinolysis. There is evidence that early coronary angiography with PCI (if the anatomy is amenable) may be preferable to a conservative strategy (angiography plus assessment of ischemic territory at risk or failure of medical management) in ACS without STE, but with elevated cardiac troponin levels. These studies, however, did not include the latest additions to the medical management armamentarium, such as the use of clopidigrel and intensive lipid modification therapy.

The authors studied 1200 patients ages 18-80 years from 42 Dutch hospitals enrolled between 2001 and 2003, examining whether an early invasive strategy (angiography within 24-48 hours of randomization, with PCI or surgical intervention as dictated by the findings on angiography) was superior to a selectively invasive strategy in patients with ACS, elevated troponin T levels, and no evidence of STE on the ECG. Patients had to have crescendo or rest symptoms of oronary ischemia that last occurred within 24 hours of randomization. In addition to elevated troponin levels, there had to be either 1) ischemic ECG changes (appropriately stringently defined ST-segment depression or T-wave inversion, or transient STE) or 2) a documented history of coronary artery disease (i.e., previous myocardial infarction, previously positive coronary angiography, or a positive exercise stress test). Exclusion criteria were numerous (see article text), centering on excluding patients with clinical or historical data that made randomization inappropriate, as well as those with recent diagnosis or treatment of ACS. All patients received an optimized medical management regimen including aspirin and enoxaparin for at least 48 hours; those who received PCI were given abciximab. Clopidigrel and aggressive lipid modification also were recommended by protocol.

Those randomized to a selectively invasive strategy were treated pharmacologically, and then went to angiography / PCI only if they exhibited breakthrough angina, hemodynamic or cardiac rhythm instability, or significant ischemia on a pre-discharge exercise stress test. The primary endpoint was the customary composite of death (from any cause), recurrent myocardial infarction (by creatine phosphokinase [CPK] criteria, liberally defined), or rehospitalization with angina within one year of randomization. Notably, patients with elevated CPK levels after PCI were classified as having a recurrent myocardial infarction.

Study groups (early invasive vs selectively invasive) were similar with regard to baseline characteristics. Cardiac catheterization was performed during the initial hospital stay in 98% of the early invasive group and 58% of the selectively invasive group; these numbers increased to 99% and 67%, respectively, at the one-year endpoint. The estimated cumulative endpoint was reached in 23% of the early invasive group as opposed to 21% of the selectively invasive group (RR 1.07; 95% CI 0.87-1.33; p = 0.33). The death rate reached 2.5% in both groups. Interestingly, the rate of myocardial infarction was higher in the early invasive group than in those managed with the selectively invasive approach (15% vs 10%, p = 0.04), yet the rehospitalization rate (for anginal symptoms) was lower in the early invasive group (7.4% vs 10.9%, p = 0.04). The authors concluded that, in the milieu of optimized medical therapy, there was no evidence favoring an early invasive over a selectively invasive approach to ACS with elevated troponin T levels but without STE on the ECG.

Commentary

This is an important paper, and the accompanying editorial is excellent.1 Termed the ICTUS trial (Invasive versus Conservative Treatment in Unstable Coronary Syndromes), this study can be added to the l-o-n-g list of annoying acronyms that are tossed around when discussing the cardiology literature. Surprisingly, the early invasive strategy did not prove superior to the selectively invasive approach in these ACS, troponin-positive patients without persistent ST-segment elevation on the ECG. Indeed, this calls into question the recommendations from the American College of Cardiology / American Heart Association, which has advocated the early invasive strategy for patients of this type with a Class IA recommendation.2

Several points must be emphasized with respect to this study, however. First, patients did well in both groups — each had a 2.5% mortality rate. So either approach is not the wrong one. Second, the definition of recurrent myocardial infarction was a liberal one; the majority of patients who had recurrent myocardial infarction (43/90 in early invasive group and 27/59 in the selectively invasive group) had a small one by enzymes — 1 to 3 times the upper limit of normal for CPK levels.

Furthermore, 68/90 in the early invasive group were periprocedural myocardial infarctions (PCI or bypass surgery). The editorial makes the point, however, that periprocedural enzyme bumps are not necessarily benign.1 Third, although the selectively invasive group had a significantly longer median time to intervention (11.8 days vs 23 hours in the early group), people still did well. Aggressive pharmacotherapy, including aspirin, clopidogrel, enoxaparin, beta-adrenergic antagonists, lipid-lowering agents, and angiotensin converting enzyme inhibitors (in select patients)2 may have evened the playing field between the early invasive and delayed invasive approach to management of ACS without ST-segment elevation on the ECG.

References

1. Boden WE. Acute coronary syndromes without ST-segment elevation – What is the role of early intervention? N Engl J Med 2005;353;1159-1161.

2. Roe MT, et al. A practical guide to understanding the 2002 ACC/AHA guidelines for the management of patients with non-ST segment elevation acute coronary syndromes. Crit Pathways Cardiol 2002;1: 129-149.