NEW ORLEANS — In patients with non-ST-segment elevation acute coronary syndromes, invasive treatment within 24 hours causes no harm, and in high-risk patients it may reduce the risk of adverse cardiovascular events, compared with delaying intervention, according to results of a large international trial.
The Timing of Intervention in Acute Coronary Syndrome (TIMACS) trial, involving 3,031 patients treated at 100 medical centers in 17 countries, “is the largest trial there will ever be on this topic. It is immediately relevant to patients, doctors, and the health care system,” said Dr. Deepak Bhatt, the study's discussant at the annual scientific sessions of the American Heart Association.
TIMACS compared the relative usefulness, safety, and cost-effectiveness of early angiography (within 24 hours), followed by revascularization if necessary, with procedures delayed more than 36 hours after the onset of unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI). Eligible patients were treated with aspirin, clopidogrel, and/or a glycoprotein IIb/IIIa antagonist in accordance with routine practice and were then randomized to receive either early or delayed intervention.
“We have very good data in patients with myocardial infarction that timely thrombolytic therapy is of utmost importance,” the principal author, Shamir R. Mehta, said in describing the rationale for the study. “But we have less information on the importance of timing in patients with unstable angina, threatened MI, or NSTEMI.”
For the primary end point, a composite of death, recurrent MI, or stroke within 6 months, the study found no significant risk reduction in favor of early intervention: 9.7% occurred in the early intervention group, compared with 11.4% in the delayed group, for a 15% relative reduction in risk that did not reach statistical significance, reported Dr. Mehta, director of interventional cardiology at Hamilton (Ont.) Health Sciences.
However, for several secondary outcome measures, differences favored early intervention. These included the composite of death, MI, and refractory ischemia, with rates of 13.1% in the delayed arm and 9.6% with early intervention; the composite of death, MI, stroke, refractory ischemia and repeat intervention, which occurred in 19.7% and 16.7%, respectively; and the outcome of repeat interventions, which occurred in 8.8% and 8.6%, respectively.
But it was the patients considered to be at the highest risk who benefited most from early intervention. Striking differences emerged when patients were stratified by the Global Registry of Acute Coronary Events (GRACE) risk score. Early diagnostic angiography reduced the relative risk of the composite end point of death, repeat MI, or stroke by 35% in a high-risk subset of patients with NSTEMI. For patients with low or intermediate risk for death with acute coronary syndromes (about two-thirds of the cohort), the slower strategy was just as effective, reported Dr. Mehta, also of McMaster University, Hamilton, Ont.
For patients with a high GRACE score (at least 140), the rate of death, MI, or stroke at 6 months was 21.6% with delayed intervention, compared with 14.1% with early treatment, a significant difference. In the low- to intermediate-risk group, the difference between the strategies was not statistically significant, at 6.7% and 7.7%, respectively.
“In the highest risk subset, early intervention appeared superior, and these patients should be taken to the cath lab as soon as possible. With others, the timing depends on additional factors. Since there are no safety concerns with early intervention, and given that it lowers refractory ischemia by about 70%, it is a reasonable routine option for all patients with ACS,” Dr. Mehta concluded.
“There has been a concern that it may be dangerous to take patients with these forms of chest pain to the catheterization lab too quickly, that a period of 'cooling off' with medical therapy may be of benefit. This has been disproved. There is no detriment to going early and there is definitely a shorter hospital stay. In high-risk patients, this trial proves there is clearly a benefit to early intervention, which is consistent with clinical common sense,” said Dr. Bhatt, chief of cardiology at the VA Boston Health Care System and director of the Integrated Interventional Cardiovascular Program at Brigham and Women's Hospital, Boston.
Early intervention 'is a reasonable routine option for all patients with ACS.' DR. MEHTA