Elsevier

The Lancet

Volume 349, Issue 9063, 17 May 1997, Pages 1429-1435
The Lancet

Articles
Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study

https://doi.org/10.1016/S0140-6736(96)10452-9Get rights and content

Summary

Background

Platelet aggregation is a dominant feature in the pathophysiology of unstable angina. Percutaneous transluminal coronary angioplasty (PTCA) in patients with this disorder carries an increased risk of thrombotic complications. Abciximab (c7E3) blocks the platelet glycoprotein IIb/IIIa receptor, thus preventing platelet adhesion and aggregation. The CAPTURE study was a randomised placebo-controlled multicentre trial to assess whether abciximab can improve outcome in patients with refractory unstable angina who are undergoing PTCA.

Methods

The study recruited patients with refractory unstable angina, defined as recurrent myocardial ischaemia under medical treatment including heparin and nitrates. Predefined stopping rules were met at a planned interim analysis of data for 1050 patients, and recruitment was stopped. Data for 1265 patients (of 1400 scheduled) are presented here. After angiography, patients received a randomly assigned infusion of abciximab or placebo for 18–24 h before PTCA, continuing until 1 h afterwards. The primary endpoint was the occurrence within 30 days after PTCA of death (any cause), myocardial infarction, or urgent intervention for recurrent ischaemia. Analyses were by intention to treat.

Findings

By 30 days, the primary endpoint had occurred in 71 (11·3%) of 630 patients who received abciximab compared with 101 (15·9%) of 635 placebo recipients (p=0·012). The rate of myocardial infarction was lower in the abciximab than in the placebo group before PTCA (four [0·6%] vs 13 [2·1%], p=0·029) and during PTCA (16 [2·6%] vs 34 [5·5%], p=0·009). Major bleeding was infrequent, but occurred more often with abciximab than with placebo (24 [3·8%] vs 12 [1·9%], p=0·043). At 6-month follow-up, death, myocardial infarction, or repeat intervention had occurred in 193 patients in each group.

Interpretation

In patients with refractory unstable angina, treatment with abciximab substantially reduces the rate of thrombotic complications, in particular myocardial infarction, before, during, and after PTCA. There was no evidence that this regimen influenced the rate of myocardial infarction after the first few days, or the need for subsequent reintervention.

Introduction

In coronary artery disease, unstable angina may develop in association with plaque fissuring or rupture, with subsequent aggregation, platelet adhesion, and intracoronary thrombosis.1, 2 An episode of unstable angina may progress to myocardial infarction or death, or may stabilise after one or more ischaemic episodes. Different classes of unstable angina have been recognised, with different event rates.3, 4 In patients who have recurrent episodes of myocardial ischaemia despite intensive medical therapy (refractory unstable angina), percutaneous transluminal coronary angioplasty (PTCA) or coronary bypass surgery is commonly used to control symptoms and to avoid progression to myocardial infarction. However, the risk of infarction and other complications during the procedure is increased in patients with unstable angina, so the risk of an early procedure must be balanced against the risk of continuing instability.5, 6

Platelet aggregation at the site of plaque rupture is a dominant feature in the pathophysiology of unstable angina. Accordingly, inhibitors of platelet aggregation may help to prevent recurrent ischaemic episodes and myocardial infarction and reduce the risk of complications during coronary intervention.7, 8 Abciximab (ReoPro, Centocor BV, Leiden, Netherlands), the Fab fragment of the chimeric antibody c7E3, is an inhibitor of platelet glycoprotein IIb/IIIa.9 Activation of this receptor is the final common pathway of the platelet response to different stimuli, leading to platelet aggregation. A pilot study in patients with refractory unstable angina suggested that treatment with abciximab during the 24 h before PTCA might help to prevent thrombotic complications.10 Furthermore, administration of abciximab during and after PTCA reduces the rate of complications associated with the procedure as well as during follow-up in patients with clinical or angiographic features indicating increased procedural risk.11, 12

The CAPTURE (c7E3 Fab antiplatelet therapy in unstable refractory angina) study was designed to assess whether abciximab, given during the 18–24 h before PTCA and continued until 1 h after PTCA, could improve outcome (avoid death, myocardial infarction, or urgent intervention) in patients with refractory unstable angina. The trial was discontinued on the recommendation of the Safety and Efficacy Monitoring Committee after interim analysis of 1050 patients (planned 1400 patients). The main results at 30 days and 6-month follow-up are presented here.

Section snippets

Patients and methods

Patients were recruited from 69 centres in 12 countries, between May, 1993, and December, 1995. Patients were eligible for CAPTURE if they had refractory unstable angina defined as: chest pain at rest with concomitant electrocardiographic (ECG) abnormalities compatible with myocardial ischaemia (ST-segment depression, ST-segment elevation, or abnormal T waves), and one or more episodes of typical chest pain, ECG abnormalities, or both, compatible with myocardial ischaemia during therapy with

Results

The CAPTURE trial was discontinued after the third interim analysis of 1050 patients. Complete data, fully reviewed by the Clinical Endpoint Committee, were available for 976 patients, and 74 patients had been reviewed partially. By that point, 87 (16·4%) of 532 patients in the placebo group and 56 (10·8%) of 518 in the abciximab group had had a primary endpoint (death, myocardial infarction, or urgent intervention within 30 days). Since the p value for the difference (p=0·0064) was below the

Discussion

In this trial, patients treated with abciximab had a 29% lower rate of the primary endpoint of death, myocardial infarction, or urgent repeat intervention up to 30 days after PTCA than patients who received placebo. The corresponding reduction in the rate of myocardial infarction was 50%. These findings accord with those of other clinical studies of abciximab10, 11, 12, 19 and studies with other inhibitors of the platelet glycoprotein IIb/IIIa receptor.20, 21 In the EPIC (Evaluation of c7E3 for

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