Examining clinical questions in acute coronary syndromes

Recent research could change standard practice.

N-acetylcysteine could prove to be useful in treating patients with acute coronary syndromes (ACS) requiring primary angioplasty, while troponin levels can't always be trusted for diagnosis, according to Will Southern, ACP Member, director of hospitalist services and associate medical director at Weiler Division Hospital of Montefiore Medical Center in New York.

The findings on N-acetylcysteine are preliminary but worth watching, said Dr. Southern, who spoke about ACS care at Hospital Medicine 2008 in San Diego in April. In a study published in 2006 in the New England Journal of Medicine, emergency department (ED) patients sent for primary angioplasty were randomly assigned to receive standard N-acetylcysteine, high-dose N-acetylcysteine or placebo. The two most noteworthy findings, Dr. Southern said, were in the incidence of contrast nephropathy and in clinical outcomes.

Thirty-three percent of people in the control group developed contrast nephropathy versus 15% and 8%, respectively, in the standard-dose and high-dose groups. Rates of unfavorable clinical outcomes (in-hospital mortality, acute renal failure requiring dialysis, or mechanical ventilation) were 18% in the control group and much lower (7% and 5%) in the N-acetylcysteine groups. Dr. Southern called the latter finding impressive, even more so when individual outcomes, such as acute renal failure and in-hospital mortality, were considered.

“It's really sort of stunning if you think about it,” he said. “These are patients who are in the ED with an ACS and have to go to the cath lab. If they're treated with N-acetylcysteine before they go, can it really be true that we're reducing their mortality?”

Although the study was small and unblinded, “I would just keep your eyes open for more work in this area because this is really a dramatic finding,” he said.

Using the cath lab for NSTEMI

Is it better to send patients with non-ST-segment elevation myocardial infarction (NSTEMI) to the catheterization laboratory immediately, or to treat them selectively and send them to the cath lab only if treatment fails? The answer depends on the type of patient, Dr. Southern said.

A 2005 New England Journal of Medicine study showed that the number of events didn't differ in patients assigned to an early invasive strategy (catheterization and percutaneous coronary intervention within 24 to 48 hours) versus a selectively invasive strategy (catheterization if optimal medical therapy failed or if clinically significant ischemia was found on noninvasive testing). But a meta-analysis published in the Journal of the American Medical Association around the same time found that patients initially managed medically had more total events overall.

“So the question is, how do we reconcile the two?”, Dr. Southern asked.

In the NEJM study, the patient population was at slightly lower risk, with a mortality rate of 2.5% versus 5% to 6% in the meta-analysis. In addition, the patients in the NEJM study were more likely to receive optimal medical therapy: All received aspirin and low-molecular weight heparin, the vast majority got intensive statin therapy, and most received clopidogrel.

“The take-home for me is that selective cath or initial medical therapy is a defensible option for patients who are lower risk and in whom we can really give optimal medical therapy,” Dr. Southern concluded.

Duration of dual-antiplatelet therapy after stents

Problems with stents arise from in-stent restenosis or thrombotic stent closure, Dr. Southern said. Although drug-eluting stents do a good job preventing the more minor events that occur with the former, that benefit may be offset in part by an increase in the latter, which ups rates of more serious events such as MI and mortality, he pointed out.

The appropriate duration of antiplatelet therapy after placement of a drug-eluting stent remains an open question because the evidence isn't yet clear, Dr. Southern said. In one study comparing bare-metal and drug-eluting stents, the bare-metal group had more events during the first six months, when all patients were receiving dual-antiplatelet therapy. After the therapy was stopped, however, event rates were higher in the drug-eluting stent group, an increase driven by cardiovascular events and MIs.

Dr. Southern recommended avoiding drug-eluting stents in patients who might not be able to adhere to clopidogrel, such as those with a history of noncompliance, those who can't afford it, and those who could need surgery in the next six months and would have to stop taking the drug. Drug-eluting stents should also arguably be avoided in patients with diabetes, Dr. Southern said.

As for how long dual-antiplatelet therapy should be continued after a drug-eluting stent is placed, Dr. Southern recommended a common-sense approach until more concrete evidence is available. “Probably we should continue dual therapy in patients for longer than a year, as long as they have a low risk of bleeding,” he said.

Trusting troponin?

In 1997, a highly publicized study found that troponin values were extremely sensitive for acute MI in patients presenting to the ED with chest pain. Patients with negative troponin values had an event rate of just 0.3% over the next 30 days.

“I remember when [the study came out]. It was great. I thought it was going to solve all my problems,” Dr. Southern said.

But in practice it's not that simple, because those findings have yet to be replicated, he pointed out. In subsequent studies, 30-day event rates in patients with negative troponin values were higher (approximately 3%), and the 72-hour event rate was low only in patients without predictors of high risk.

“For me, the first result [the 1997 study] was really the outlier,” Dr. Southern said. In that study, he pointed out, the median duration of patients' chest pain was five hours.

“It sort of makes clinical sense to me that if you've had chest pain for five hours and your troponins were negative, maybe it was not coronary related. But if someone has had chest pain for five or 10 minutes and has negative troponins, maybe I'm not so sure,” he said. “We can't just blindly say ‘negative troponins make everything OK.’ We have to bring some clinical stuff in.”

Risk stratification tools, such as the TIMI Risk Score, can help, Dr. Southern said. However, even in patients with low risk scores, the event rates are not zero. No matter what tools you use, he said, the best way to stratify risk is to find patients in whom you feel comfortable excluding ACS.

“The patients I feel comfortable with are those who have prolonged chest pain and negative troponins; those with normal EKGs and normal troponin (with the caveat that you can be fooled in diabetics and younger or older patients); and patients with normal troponins and atypical symptoms, excluding diabetics and those over the age of 65,” he said. For other patients, a stress test is appropriate.

To stress or not to stress

Although noninvasive stress tests have poor sensitivity, they're very useful for prognosis, “which is really our job when we're dealing with people with undifferentiated chest pain,” Dr. Southern said.

But although ordering a stress EKG is a reasonable strategy when you're trying to prognosticate quickly about coronary events, the test can't be done on everyone because of the risk for nondiagnostic results. Stress EKG is contraindicated in the following situations, according to Dr. Southern:

  • Left bundle-branch block (vasodilator pharmacologic);
  • Left ventricular hypertrophy;
  • Digoxin therapy;
  • ST abnormalities;
  • Paced rhythm;
  • Pre-excitation; and
  • Inability to exercise

In patients with baseline ECG abnormalities, exercise perfusion testing or exercise echocardiography can be used. If a patient is unable to exercise, pharmacologic perfusion imaging or echocardiography is the test of choice, while adenosine or dipyridamole perfusion imaging should be ordered in those with left bundle-branch block, Dr. Southern said.

The bottom line, he concluded, is to be cautious in patients who have suspected ACS.

“When you're dealing with these patients, you're in a little bit of a danger area,” he said. “So just tread carefully and be careful what you do.”