TIMACS Published, Supports Early Intervention in High-Risk Non-STEMI ACS

May 20, 2009

May 20, 2009 (Boston, Massachusetts)— Whether invasive management was carried out early or delayed didn't make a significant difference to the primary end point of death, MI, or stroke at six months in a randomized trial called Timing of Intervention in Acute Coronary Syndromes (TIMACS), which entered patients with non-ST-segment-elevation MI (non-STEMI) ACS [1].

The study, previously reported and now published in the May 21, 2009 issue of the New England Journal of Medicine, also suggested that early intervention may have reduced patients' risk of death, MI, or refractory ischemia, a prespecified secondary end point. The difference was driven by a sharp decrease in the rate of refractory ischemia.

TIMACS further suggested that patients with GRACE scores categorizing them as high risk benefited significantly from early intervention with respect to both composite end points. Safety outcomes, such as bleeding rates, were similar with the two strategies.

The findings suggest that "routine early intervention may be a preferred option for patients with acute coronary syndromes when access to cardiac catheterization and PCI capability is readily available," write the authors, led by Dr Shamir R Mehta (McMaster University, Hamilton, ON). "When access to these facilities is not readily available (eg, on weekends or after hours), the results of our study provide reassurance that patients who are not at high risk can undergo interventions less urgently."

The group's published numbers and conclusions are virtually the same as those Mehta preliminarily presented at the American Heart Association 2008 Scientific Sessions, as covered by heartwire at the time.

In TIMACS, 3031 patients with non-STEMI ACS were randomized to early intervention (n=1593) or delayed intervention (n=1438). "Early" meant that patients went to the catheterization laboratory within 24 hours of presenting. "Delayed" was defined as at least 36 hours later.

Prespecified TIMACS End Points at Six Months, Hazard Ratios (HR) for Early vs Delayed Intervention, Overall and Stratified by GRACE Risk Scores

End point

HR (95% CI)

Death, MI, or stroke*

0.85 (0.68–1.06)

Death, MI, or refractory ischemia

0.72 (0.58–0.89)

Death, MI, or stroke, high-risk GRACE scores

0.65 (0.48–0.89)

Death, MI, or stroke, low- to intermediate-risk GRACE scores

1.12 (0.81–1.56)

*Primary end point

"The treatment of patients with acute coronary syndromes is optimal when the intensity of therapy, both medical and nonmedical (coronary angiography and revascularization), is tailored to the patient's risk of an ischemic cardiac event or a treatment-related complication," observe Drs L David Hillis and Richard A Lange (University of Texas Health Science Center, San Antonio) in an editorial accompanying TIMACS [2]. "The magnitude of benefit correlates with the patient's level of risk."

(The editorial from Hillis and Lange also covers the EARLY-ACS trial, published in the same issue, which compared "early" and "delayed" provisional treatment with the glycoprotein IIb/IIIa receptor blocker eptifibatide in invasively managed high-risk ACS patients. That study had been presented at the American College of Cardiology 2009 Scientific Sessions and, along with its early-release online publication [3], was covered then by heartwire.)

TIMACS was partially supported by GlaxoSmithKline, Sanofi-Aventis, and Organon International; disclosures for individual coauthors are in the report. Hillis and Lange report no conflicts.