No difference in outcomes for delayed treatment of non-STEMI patients
NEW ORLEANS—While there is strong evidence that getting to the hospital quickly during a heart attack is critical, the TIMACS trial has found that there is no significant difference between an early and a delayed invasive strategy for prevention of death, MI or stroke, according to a late-breaking clinical trial presented Monday at the American Heart Association (AHA) Scientific Sessions.

Shamir R. Mehta, MD, director of interventional cardiology at Hamilton Health Sciences in Hamilton, Ontario, presented the findings of the randomized, controlled TIMACS (TIMing of intervention in patients with Acute Coronary Syndrome) trial.

The study of 3,031 patients treated at 100 medical centers in 17 countries was a prospective comparison of the relative usefulness and safety of early (within 24 hours) angiography, followed by revascularization if necessary, compared to a delay of more than 36 hours after the onset of unstable angina or non-STEMI.

Mehta said that the primary endpoint was a composite of death, new MI or stroke at six months.

An early diagnostic angiogram reduced the relative risk of the composite endpoint of death, second heart attack or stroke by 35 percent in a high-risk subset of patients with a heart attack not demonstrating ST-segment elevation on the EKG. Yet, for many patients, the slower strategy appears to be just as good, according to Mehta.

“If you are at low risk or intermediate risk for death with ACS, it doesn’t matter whether you have your angiogram early or late, but if you are at high risk, the early intervention strategy is far better,” he said.

About two-thirds of the patients in the study were in the low- or intermediate-risk groups.  

For the primary endpoint, Mehta reported that there was no significant risk reduction (p value 0.15) in favor of early intervention. However, he said that striking results emerged when the researchers compared patients based on their Grace Risk Score in a subgroup analysis, which predicts the risk of dying within the next six months based on factors like age, other medical conditions, kidney function and a history of heart failure.

Among the 961 patients who measured >140 on the Grace Risk Score, the primary endpoint was seen in 21.6 percent of the late intervention group versus 14.1 percent of the high-risk patients—a 35 percent reduction in relative risk that was of high statistical significance, which Mehta said indicates a clear benefit for early coronary angiography and treatment.
He noted that with non-STEMI patients, unlike with STEMI patients, “there is no imperative to proceed rapidly to the cath lab. In fact, some have hypothesized that it may be harmful to do so, because if the patient needs a PCI, the procedure would be performed on a recently ruptured plaque with a fresh thrombus. The thought was that those conditions could lead to increased complications and higher event rates.”

However, several studies comparing STEMI and non-STEMI heart attacks have found that STEMI patients tend to fare better, leading to the hypothesis that the timing of treatment may be a factor, Mehta said.

“If the early strategy is better than delayed in the high-risk patients then it might be appropriate to bypass small hospitals that lack invasive facilities and take those patients directly to an invasive center,” he commented.

However, the study also found that early invasive strategy had a large impact on reducing the rate of refractory ischemia by 70 percent.

Deepak Bhatt, MD, from Brigham and Women’s Hospital in Boston, who commented on the study, said TIMACS is the most important interventional trial being presented at AHA this year, noting that this is the largest trial on this topic. It has “immediate relevance,” he said.

According to Bhatt, it is important for providers because it will determine whether an interventionalist needs to be called in to the hospital during off-hours to immediately treat non-STEMI patients. However, he stressed that there is a benefit for early intervention for those patients with the highest risk.