Timing of Catheterization in ACS

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco. Dr. Boyle reports no financial relationships relevant to this field of study.

Source: Sorajja P, et al. Impact of delay to angioplasty in patients with acute coronary syndromes undergoing invasive management: Analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial. J Am Coll Cardiol. 2010;55:1416-1424.

Non-ST elevation (NSTE) acute coronary syndromes (ACS) can be managed by either an early invasive or early conservative strategy, with most data favoring an early invasive strategy in moderate- and high-risk patients. The most appropriate timing for intervention in patients being managed with an early invasive approach is the subject of some debate. Although there is a clear advantage to early revascularization in ST-elevation myocardial infarction, in NSTE-ACS it is not clear whether to delay and let the lesion "cool down" with anticoagulants/anti-platelet agents or proceed straight to the cath lab. Clinical studies have yielded conflicting results on this issue. Thus, Sorajja et al examined the ACUITY trial data to determine the effect of delay to angiography and intervention on outcomes in their patient population.

The ACUITY trial was a prospective, open-label, randomized, multicenter trial in which patients with NSTE-ACS undergoing an early invasive management strategy were randomized to receive one of three antithrombotic regimens: 1) unfractionated or low molecular weight heparin plus a glycoprotein IIb/IIIa inhibitor; 2) bivalirudin plus a glycoprotein IIb/IIIa inhibitor; or 3) bivalirudin alone. Patients were eligible for study participation if they were ≥ 18 years of age with symptoms of NSTE-ACS within the preceding 24 hours and if one or more of the following high-risk criteria were met: new ST-segment depression or transient elevation of ≥ 1 mm; elevations in the troponin I, troponin T, or creatine kinase-MB levels; known coronary artery disease; or all four other variables for predicting Thrombolysis In Myocardial Infarction (TIMI) risk scores for unstable angina. Exclusion criteria were ST-segment elevation MI or cardiogenic shock; bleeding diathesis or major bleeding episode within two weeks; thrombocytopenia; a calculated creatinine clearance rate of < 30 mL/min; recent administration of abciximab, warfarin, fondaparinux, fibrinolytic agents, bivalirudin, or two or more doses of low molecular weight heparin; and allergy to any of the study drugs or to iodinated contrast medium that could not be controlled in advance with medication. Follow-up was performed at one month and 12 months. Three primary endpoints at 30 days were prespecified: composite ischemia (death from any cause, MI, or unplanned revascularization for ischemia), major bleeding (not related to coronary artery bypass grafting [CABG]), and net adverse clinical events (composite ischemia or major bleeding).

Results: Of the 13,819 patients enrolled in the ACUITY study, 7,749 patients underwent percutaneous coronary intervention (PCI) at the discretion of the operator. There were significant differences in the baseline demographics and angiographic features in the groups who had PCI < 8 hours, 8-24 hours, and > 24 hours after hospitalization. Patients who had delayed PCI more frequently had elevation of cardiac troponins, high TIMI risk score (5 to 7), left main culprit lesion, baseline TIMI flow grade 3, prior history of diabetes mellitus, MI, left main disease, CABG, and prior use of antithrombins and thienopyridines. There was no difference in procedural success after PCI for the three patient groups.

Delay in angiography > 24 hours was a significant predictor of death at 30 days and one year. After multivariable risk adjustment, patients whose PCI was delayed > 24 hours after admission had higher rates of death (hazard Ratio [HR] 2.1; p < 0.001) and death or MI (HR 1.5; p < 0.001) at 30 days. This was also seen at 12 months (death HR 1.6, death or MI HR 1.4; both p < 0.001). This relationship between delay and adverse outcomes was apparent across all levels of risk by TIMI risk score, and across all three anticoagulant regimen randomization groups. The authors conclude that delaying revascularization with PCI > 24 hours in patients with NSTE-ACS was an independent predictor of early and late mortality and adverse ischemic outcomes.

Commentary

Several studies have examined the optimal timing of catheterization and PCI in patients presenting with ACS. The TIMACS study (N Engl J Med. 2009;360:2165-2175) suggested that earlier intervention (median 14 hours after admission) was superior to delayed intervention (median 50 hours) but only in high-risk patients. Analysis from the GRACE registry (Am J Cardiol. 2005;12:1397-1403) suggested the opposite: that delaying angiography was associated with better outcomes. The ABOARD study (JAMA. 2009;302:947-954) compared immediate angiography (average one hour) vs. delay until the next working day (average 21 hours). They showed no benefit to immediate cardiac catheterization. The current study by Sorajja et al suggests that PCI should be performed expeditiously, but not necessarily immediately upon admission. Their findings are consistent with both the TIMACS study and the ABOARD study, suggesting that catheterization should be performed within approximately 24 hours. However, studies that challenge that premise remain. It is important to note that this was not a randomized, controlled trial; it was a retrospective analysis, and we should not change management decisions based on post-hoc analyses such as this alone. However, the study is strengthened by the fact that it was performed on a large dataset with contemporary anticoagulant, anti-platelet, and PCI strategies. Clinicians should consider higher-risk ACS patients for early angiography and possible PCI, and in the absence of hemodynamic instability or ongoing ischemia, the optimal window for PCI seems to be within the first 24 hours.