Medical Grand Rounds

Controversies in non-ST-elevation acute coronary syndromes and percutaneous coronary interventions

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ABSTRACTNon-ST-elevation myocardial infarction (MI) and unstable angina represent the majority of acute coronary syndromes. Recent studies have helped clarify treatment strategies. Drug-eluting stents have reduced the problem of restenosis, but questions remain about the length of time patients need dual antiplatelet therapy.


  • The data favor an aggressive strategy of routine catheterization, rather than a conservative strategy of catheterization only if a patient develops recurrent, spontaneous, or stress-induced ischemia.
  • Early percutaneous intervention (within 24 hours) may be beneficial in patients at higher risk, but not necessarily in those at lower risk.
  • Drug-eluting stents appear safe, assuming dual antiplatelet therapy is used. It is unclear how long this therapy needs to be continued.
  • The choice of revascularization strategy—bypass surgery, bare-metal stent, or drug-eluting stent—should be individualized based on the risk of restenosis, thrombosis, and other factors.



Despite all the attention paid to ST-segment-elevation myocardial infarction (MI), in terms of sheer numbers, non-ST-elevation MI and unstable angina are where the action is. Acute coronary syndromes account for 2.43 million hospital discharges per year. Of these, 0.46 million are for ST-elevation MI and 1.97 million are for non-ST-elevation MI and unstable angina.1,2

A number of recent studies have begun to answer some of the pressing questions about treating these types of acute coronary syndromes. In this article, I update the reader on these studies, along with recent findings regarding stenting and antiplatelet agents. As you will see, they are all interconnected.


In the 1990s, a topic of debate was whether patients presenting with unstable angina or non-ST-elevation MI should routinely undergo catheterization or whether they would do just as well with a conservative approach, ie, undergoing catheterization only if they developed recurrent, spontaneous, or stress-induced ischemia. Now, the data are reasonably clear and favor an aggressive strategy.3

Mehta et al4 performed a meta-analysis of seven randomized controlled trials (N = 9,212 patients) of aggressive vs conservative angiography and revascularization for non-ST-elevation MI or unstable angina. The results favored the aggressive strategy. At 17 months of follow-up, death or MI had occurred in 7.4% of patients who received the aggressive therapy compared with 11.0% of those who received the conservative therapy, for an odds ratio of 0.82 (P = .001).

The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implemention of the ACC/AHA Guidelines?) Quality Improvement Initiative5 analyzed data from a registry of 17,926 patients with non-ST-elevation acute coronary syndrome who were at high risk because of positive cardiac markers or ischemic electrocardiographic changes. Overall, 2.0% of patients who received early invasive care (catheterization within the first 48 hours) died in the hospital compared with 6.2% of those who got no early invasive care, for an adjusted odds ratio of 0.63 (95% confidence interval [CI] 0.52–0.77).

The investigators also stratified the patients into those at low, medium, and high risk, using the criteria of the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin [eptifibatide] Therapy) risk score. There were fewer deaths with early invasive therapy in each risk group, and the risk reduction was greatest in the high-risk group.5

Bavry et al6 performed an updated meta-analysis of randomized trials. At a mean follow-up of 24 months, the relative risk of death from any cause was 0.75 in patients who received early invasive therapy.

In another meta-analysis, O’Donoghue et al7 found that the odds ratio of death, MI, or rehospitalization with acute coronary syndromes was 0.73 (95% CI 0.55–0.98) in men who received invasive vs conservative therapy; in women it was 0.81 (95% CI 0.65–1.01). In women, the benefit was statistically significant in those who had elevations of creatine kinase MB or troponin but not in those who did not, though the benefit in men appeared to be less dependent on the presence of biomarker abnormalities.


Although a number of trials showed that a routine invasive strategy leads to better outcomes than a conservative strategy, until recently we had no information as to whether the catheterization needed to be done early (eg, within the first 24 hours) or if it could be delayed a day or two while the patient received medical therapy.

Mehta et al8 conducted a trial to find out: the Timing of Intervention in Acute Coronary Syndrome (TIMACS) trial. Patients were included if they had unstable angina or non-ST-elevation MI, presented to a hospital within 24 hours of the onset of symptoms, and had two of three high-risk features: age 60 years or older, elevated cardiac biomarkers, or electrocardiographic findings compatible with ischemia. All received standard medical therapy, and 3,031 were randomly assigned to undergo angiography either within 24 hours after randomization or 36 or more hours after randomization.

At 6 months, the primary outcome of death, new MI, or stroke had occurred in 9.6% of the patients in the early-intervention group and in 11.3% of those in the delayed-intervention group, but the difference was not statistically significant. However, the difference in the rate of a secondary end point, death, MI, or refractory ischemia, was statistically significant: 9.5% vs 12.9%, P = .003, owing mainly to less refractory ischemia with early intervention.

The patients were also stratified into two groups by baseline risk. The rate of the primary outcome was significantly lower with early intervention in high-risk patients, but not in those at intermediate or low risk. Thus, early intervention may be beneficial in patients at high risk, such as those with ongoing chest pain, but not necessarily in those at low risk.


Coronary artery disease often affects more than one segment. Until recently, it was not known whether we should stent all stenotic segments in patients presenting with non-ST-elevation MI or unstable angina, or only the “culprit lesion.”

Shishehbor et al9 examined data from a Cleveland Clinic registry of 1,240 patients with acute coronary syndrome and multivessel coronary artery disease who underwent bare-metal stenting. The median follow-up was 2.3 years. Using a propensity model to match patients in the two groups with similar baseline characteristics, they found that the rate of repeat revascularization was less with multivessel intervention than with culprit-only stenting, as was the rate of the combined end point of death, MI, or revascularization, but not that of all-cause mortality or the composite of death or MI.


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