Timing is everything for some heart attack patients

There is strong evidence that getting to the hospital quickly during a heart attack is critical, since early treatment saves both lives and heart muscle. And if the responsible coronary artery is completely blocked, it should be opened as soon as possible.

What about patients with incomplete blockages, who have ACS or acute coronary syndrome? They should get to the hospital just as fast, but once there and on medical treatment, do they need to race to the cath lab? Not always, researchers said, regarding the TIMing of Intervention in Acute Coronary Syndrome (TIMACS) study they presented as a late-breaking clinical trial at the American Heart Association's Scientific Sessions 2008.

The study of 3,031 patients treated at 100 medical centers in 17 countries was a prospective comparison of the relative usefulness, safety and cost effectiveness of early (within 24 hours) angiography, followed by revascularization if necessary, versus a delay of more than 36 hours after the onset of unstable angina (chest pain) or non-ST segment elevation heart attack.

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. But for many patients, the slower strategy appears to be just as good.

"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," said Shamir R. Mehta, M.D., M.Sc., study author, director of interventional cardiology at Hamilton Health Sciences Corp. and associate professor of medicine at McMaster University, Hamilton, Canada.

About two-thirds of the patients in the study were in the low or intermediate risk groups. The study of 3,031 patients treated at 100 medical centers in 17 countries was a prospective comparison of the relative usefulness, safety and cost effectiveness of intervention as soon as possible (and within 24 hours) versus a delay of more than 36 hours after unstable angina (chest pain) or non-ST segment elevation acute coronary syndrome (ACS), a common type of heart attack.

For the primary endpoint, a composite of death, recurrent heart attack or stroke within six months, the researchers found no significant risk reduction (p value 0.15) in favor of early intervention. However, striking results emerged when the researchers compared patients based on their Grace Risk Score, a way of predicting 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 (p value = 0.005), indicating a clear benefit for early coronary angiography and treatment, he said.

"This is by far, the largest study of ACS to study the ideal timing for intervention," he said, adding that an earlier trial on the issue was too small to provide a conclusive answer.

"Randomized trials have shown the benefit of coronary artery bypass grafting and percutaneous coronary intervention (PCI) in patients with this form of acute coronary syndrome (ACS), however the optimal timing of those interventions is unknown," he said.

A heart attack occurs when the blood supply to part of the heart through a coronary artery is severely reduced or stopped. The reduction or stoppage happens when one or more of the coronary arteries supplying blood to the heart muscle are blocked. This is usually caused by the buildup of plaque (deposits of fat-like substances), a process called atherosclerosis. The plaque can eventually fracture, creating a place where a blood clot forms and blocks the artery, leading to a heart attack.

When most people think of heart attack they think of ST-elevation myocardial infarction (STEMI), an emergency situation in which the patient has a complete blockage in an artery. Those patients usually should get clot-busting drugs, balloon angioplasty or bypass surgery within minutes or hours of symptom onset.

"Non-ST-elevation myocardial infarction (non-STEMI) patients have less than a complete blockage and their chest pain tends to subside in response to initial medical treatment. Therefore, unlike STEMI, there is no imperative to proceed rapidly to the cath (catheterization) 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 (blood clot). The thought was that those conditions could lead to increased complications and higher event rates," he said.

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.

Coronary angiography is an invasive diagnostic imaging technique in which a catheter is threaded through the blood vessels to the arteries around the heart so that a contrast medium can be injected to make the area visible by X-ray. Angiography may not be available at small, rural hospitals, he 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 said.

Co-authors are: The TIMACS study group. Individual author disclosures are available on the abstract.

The study was funded by the Canadian Institutes of Health Research (CIHR).