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 [percutaneous coronary intervention] 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.
References
- Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009; 360:2165-2175.
- Hillis DL, Lange RA. Optimal management of acute coronary syndromes. N Engl J Med 2009; 360:2237-2240.
Clinical Context
There are many treatment options for patients with ACS, and an editorial by Hillis and Lange, which accompanies the current article, reviews recommendations for medical treatment for these critical patients. All patients with ACS and no contraindications to treatment should receive immediate treatment with aspirin and clopidogrel as well as statins and antianginal medications. Although patients at low risk may receive unfractionated heparin, patients at high risk may benefit from the addition of glycoprotein IIb/IIIa inhibitors to the anticoagulation regimen.
High-risk patients with ACS also benefit from coronary angiography and revascularization, but the ideal timing for these procedures remains unclear. The current study addresses this issue.
Study Highlights
- Patients eligible for study participation had unstable angina or myocardial infarction without ST-segment elevation. All participants also met at least 2 of the following criteria:
- Age 60 years or older
- Cardiac biomarkers above the upper limit of the normal range
- Results on electrocardiography compatible with ischemia
- Participants were assigned to undergo early (<>
- The primary outcome of the study was the composite of death, new myocardial infarction, or stroke at 6 months. Researchers also evaluated a planned secondary outcome, which included the composite of death, myocardial infarction, or refractory ischemia at 6 months.
- 3031 patients underwent randomization. The mean age was 65 years, and slightly more than one third of participants were women. Approximately 20% had a history of a previous coronary procedure. The rate of evidence-based medical treatment of ACS was high in both groups.
- The median times to angiography in the early and delayed treatment groups were 14 and 50 hours, respectively.
- The primary outcome occurred among 9.6% of the early treatment group and 11.3% of the delayed treatment group at 6 months, a nonsignificant difference. There was also no difference between groups in the individual risks for death, new myocardial infarction, and stroke.
- However, participants in the early group experienced significantly lower rates of the secondary composite outcome of death, myocardial infarction, or refractory ischemia at 6 months (9.5% vs 12.9%; hazard ratio, 0.72). This difference was mainly the result of a lower rate of refractory ischemia in subjects receiving early vs delayed treatment (1.0% vs 3.3%), and the presence of refractory ischemia increased the risk for subsequent myocardial infarction by a factor of 4.
- The rate of heart failure was similar between groups.
- The rate of repeated coronary intervention was slightly higher in the early treatment group vs the delayed treatment group at 30 days (5.9% vs 4.2%).
- The rate of major bleeding events was similar between groups.
- Subgroup analysis based on age and sex failed to alter the main study outcome.
- In patients at high cardiovascular risk, early treatment was associated with improved outcomes vs delayed treatment for both the primary composite outcome (hazard ratio, 0.65) outcome and secondary composite outcome (hazard ratio, 0.62).
- Among participants at a low risk for cardiovascular events, there was no difference between early and delayed treatment in any study outcome.
- There were no significant differences in outcomes among participants who received early angiography at less than 6 hours, 6 to 12 hours, or more than 12 hours.
Clinical Implications
- All patients with ACS and no contraindications to treatment should receive immediate treatment with aspirin and clopidogrel as well as statins and antianginal medications. Although patients at low risk may receive unfractionated heparin alone for anticoagulation, patients at high risk may benefit from the addition of glycoprotein IIb/IIIa inhibitors to the anticoagulation regimen.
- In the current study, early angiography for patients with ACS did not improve the primary composite outcome of death, myocardial infarction, or stroke vs delayed angiography. However, early angiography was superior in a secondary outcome, which included refractory ischemia, and it was also superior overall in high-risk patients.
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