Eptifibatide reduced deaths and nonfatal myocardial infarction in acute coronary syndromes
ACP J Club. 1999 Jan-Feb;130:1. doi:10.7326/ACPJC-1999-130-1-001
The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998 Aug 13;339:436-43.
In patients who have acute coronary syndromes without persistent ST-segment elevation, can the inhibition of platelet aggregation with eptifibatide decrease mortality and nonfatal infarction?
30-day randomized, double-blind, placebo-controlled trial.
726 hospitals in 28 countries.
10 948 patients who had symptoms of ischemic chest pain at rest for ≥ 10 minutes in the previous 24 hours and transient ST-segment elevation > 0.5 mm, ST-segment depression > 0.5 mm, T-wave inversion > 1 mm within 12 hours of chest pain, or serum creatine kinase-MB level above the upper limit of normal. Exclusion criteria included persistent ST-segment elevation > 1 mm, bleeding diathesis, gastrointestinal or genitourinary bleeding in the previous 30 days, systolic blood pressure > 200 mm Hg or diastolic blood pressure > 110 mm Hg, nonhemorrhagic stroke in the previous 30 days, history of hemorrhagic stroke, renal failure, or pregnancy.
All patients received aspirin, 80 to 325 mg/d, and heparin, 5000 U bolus plus 1000 U/hr infusion. Patients were allocated either to low-dose eptifibatide, 180 U/kg of body weight bolus dose plus an infusion of 1.3 U/kg per minute (n = 1487); high-dose eptifibatide, 180 U/kg bolus dose plus an infusion of 2.0 U/kg per minute (n = 4722); or a bolus and infusion of placebo (n = 4739) for 72 hours or until discharge. The primary comparison groups were the high-dose and placebo groups (median age 64 y, 64% men).
Main outcome measures
The combined end point of death plus nonfatal myocardial infarction (MI) at 30 days. Secondary outcome measures included death or nonfatal MI within 30 days, the combined end point at 4 days and at 7 days, and bleeding and stroke rates.
The combined end point occurred less often in the eptifibatide group than in the placebo group at 4 days (P = 0.01), 7 days (P = 0.02), and 30 days (P = 0.04) (Table). Fewer nonfatal MIs at 4 days (7% vs 8%, P = 0.03) occurred in the eptifibatide group than in the placebo group. More patients in the eptifibatide group than in the placebo group had bleeding (24% vs 17%, P = 0.02 for minor or major bleeding). No differences existed between groups for other secondary outcomes.
In patients with acute coronary syndromes who did not have persistent ST-segment elevation, eptifibatide led to reduced combined death and nonfatal MI and increased bleeding.
Sources of funding: COR Therapeutics and Schering-Plough Research Institute.
For correspondence: Dr. R.A. Harrington, Duke Clinical Research Institute, 2024 West Main Street, Durham, NC 27705, USA. FAX 919-668-7072.
Table. Eptifibatide (EP) vs placebo for acute coronary syndromes*
|Outcomes||EP||Placebo||RRR (95% CI)||NNT (CI)|
|Death or nonfatal MI at 30 d||14%||16%||9% (0 to 18)||68 (35 to 1920)|
|Death or nonfatal MI at 7 d||10%||12%||13% (2 to 22)||67 (37 to 399)|
|Death or nonfatal MI at 4 d||8%||9%||16% (4 to 27)||68 (39 to 265)|
*MI = myocardial infarction. Other abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
The overall benefit observed in the PURSUIT trial is small: a 1.5% absolute reduction in death or MI. The risk for severe bleeding was increased by 16% or 67%, depending on the definition.
Although not documented or discussed in this report, the reduction in the combined end point was almost entirely restricted to the subgroup of patients who had an early revascularization procedure. 74 fewer events occurred in the eptifibatide group than in the placebo group, with 68 (92%) of these events occurring in the subgroup with early revascularization (24% of the total group).
The observed treatment effect varied among geographic regions: The effect was the greatest in North America, followed by western Europe, Latin America, and eastern Europe. This variation can be explained by differences in the absolute risks in the placebo group (figures not shown in the article) or in the rate of early revascularization. The latter hypothesis is supported by the wide regional variations in the frequency of cardiac catheterization: 79% in North America, 58% in western Europe, 46% in Latin America, and 20% in eastern Europe.
PURSUIT is the first trial of eptifibatide with a large study population. Its results confirm those of previous trials on GIIb/IIIa receptor antagonists (abciximab, tirofiban, or eptifibatide) in patients who had coronary balloon angioplasty or atherectomy. However, further trials are needed to show a benefit of such antagonists in patients with acute coronary syndrome who do not pursue coronary revascularization. In addition, because women did not benefit from the treatment in PURSUIT, further trials and retrospective analysis of the current study are required to clarify this point. Also, the benefit in low-risk patients should be evaluated carefully. Physicians should wait for publication of these data before extending the use of GIIb/IIIa-receptor antagonists to patients who are not selected for revascularization.
Jean-Pierre Boissel, MD
Université Claude BernardLyon, France