Abciximab for Unstable Angina in Patients with Elevated Troponin T

Source: Hamm CW, et al. N Engl J Med 1999;340:1623-1629.

This study is an important subgroup analysis from the c7E3 Fab Antiplatelet Therapy in Unstable Refactory Angina (CAPTURE) trial. In the earlier study, the glycoprotein IIb/IIIa-receptor blocker abciximab (ReoPro) was shown to reduce the risk of myocardial infarction (MI) in patients with refractory unstable angina.1 This study looks more closely at the prognostic value of troponin T and the effect of abciximab on risk of adverse outcome in relation to troponin T level. The patients had recurrent chest pain at rest associated with ECG changes consistent with ischemia and continued to have chest pain despite treatment with IV heparin and nitroglycerin. All patients had significant coronary artery disease documented by angiography. Patients were excluded if they had sustained an MI within the prior two weeks.

Suitable patients were given abciximab 0.25 mg/kg IV bolus followed by a 10 mcg/min infusion or a matching placebo. Subjects were scheduled for percutaneous transluminal coronary angioplasty (PTCA) the day after study medication was given. Study end points were death, MI, unscheduled PTCA, and coronary bypass surgery.

Of the 1265 patients in the CAPTURE trial, 890 met criteria for inclusion in this study. Subjects were grouped according to troponin T levels at study entry. Among the 615 patients with normal troponin T levels, the risk of death or MI was 8% and was not improved by abciximab treatment. However, the effect of abciximab was striking among the 275 patients with elevated troponin T levels (> 0.1 ng/mL): 7.5% of abciximab-treated patients experienced death or MI within six months, compared to 24% of placebo-treated patients. The relative risk of death or MI associated with abciximab treatment was 0.32 in patients with elevated troponin T levels. The authors conclude that troponin T elevation identifies a subgroup of patients at high risk of death or MI and that this group will benefit considerably from treatment with abciximab.

Comment by David J. Karras, MD, FAAEM, FACEP

Unstable angina carries with it a high risk of MI and/or death within several months of onset. The rate of adverse events in placebo-treated patients (despite therapy with heparin and nitroglycerin) in this study is strikingly high and consistent with earlier studies. Furthermore, this study confirms that troponin T elevation greatly increases the risk of mortality and infarction. Troponin T is an extremely sensitive and specific marker of myocardial injury. Elevated troponin T levels in patients without a rise in creatine kinase is thought to reflect focal myocyte necrosis from embolization of thrombi released from a disrupted coronary plaque. Since such plaque disruption precedes coronary occlusion, troponin T elevation often heralds an impending major infarction or sudden cardiac death.

Certain caveats must be condidered before applying this study’s finding to patients in the ED. Most importantly, abciximab was not used as primary therapy for unstable angina. The patients in this study all had recurrent chest pain despite management with heparin and nitroglycerin. All subjects were demonstrated to have significant coronary artery disease; the results may not be applicable to "all comers" presenting with angina-like chest pain to the ED. Nonetheless, it is important that emergency physicians be familiar with the glycoprotein IIb/IIIa-receptor blockers. Several articles discussing the role of these drugs from an ED perspective appear in a recent issue of Journal of Emergency Medicine (1999;17:565-595).

Reference

1. The CAPTURE investigators. Lancet 1997;349: 1429-1435.