Elsevier

The Lancet

Volume 358, Issue 9281, 18 August 2001, Pages 527-533
The Lancet

Fast track — Articles
Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study

https://doi.org/10.1016/S0140-6736(01)05701-4Get rights and content

Summary

Background

Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI.

Methods

2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat.

Findings

There were no drop-outs. 59 (4·5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6·4%) in the placebo group (relative risk 0·70 [95% CI 0·50–0·97], p=0·03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0·03), and of cardiovascular death or myocardial infarction (p=0·047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0·002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0·001). At follow-up, there was no significant difference in major bleeding between the groups (p=0·64).

Interpretation

In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.

Introduction

Antiplatelet therapy is an important adjunctive treatment that reduces ischaemic complications in patients undergoing percutaneous coronary intervention (PCI)1, 2, 3, 4, 5. Ischaemic events after PCI are mainly the result of a platelet-dependent process that results in thrombosis at the site of mechanical plaque disruption and distal embolisation of platelet thrombi into the coronary microcirculation.6, 7, 8, 9 Although treatment with aspirin before PCI (pretreatment) reduces cardiac events, a substantial risk still remains. Therefore, there is a need to develop more effective antiplatelet strategies that can be given before PCI, with the goal of reducing events after the procedure.

In addition to pretreatment, long-term oral administration of antiplatelet therapy after PCI might also be beneficial because atherothrombosis is a generalised vascular disease that affects not only the target coronary lesion, but also other vascular territories. Despite the beneficial effects of long-term treatment with aspirin after PCI, there remains a significant risk of major cardiovascular events.10, 11, 12, 13 Although the intravenous glycoprotein IIb/IIIa inhibitors improve clinical outcomes when given for a short time,5, 14 longer term oral administration of these agents has not been effective, and might even be harmful.12, 15 Whether other, more effective long-term antiplatelet regimens can add to the beneficial effects of aspirin after PCI is currently unknown.

Clopidogrel is an oral antiplatelet agent of the thienopyridine class, which selectively and irreversibly inhibits the platelet ADP receptor. When clopidogrel is given with aspirin, the antiplatelet effect is synergistic.16, 17, 18 This observation has been confirmed clinically in patients receiving intracoronary stents, in whom ticlopidine plus aspirin given after PCI for about 4 weeks was superior to aspirin alone or aspirin plus oral anticoagulation.19

The PCI CURE study was designed to test the hypothesis that, in addition to aspirin, treatment with clopidogrel before PCI is superior to placebo in preventing major ischaemic events afterwards. The second objective of the study was to determine whether long-term treatment with clopidogrel for up to 1 year after PCI would result in additional clinically relevant benefit.

Section snippets

Patients

PCI-CURE was a prospectively designed study of patients undergoing PCI who were randomised to double-blind therapy with clopidogrel or placebo in the Clopidogrel in Unstable angina to prevent Recurrent ischaemic Events (CURE) trial.19

The inclusion and exclusion criteria for the CURE trial have been described previously.19 Briefly, patients were eligible for inclusion if they had had symptoms indicative of acute coronary syndrome within the past 24 h and if they did not have ST-segment elevation

Results

Overall, 2658 of the 12 562 patients in the CURE trial underwent PCI. 1313 were assigned clopidogrel and 1345 placebo. No patients were lost to follow-up (figure 1). 1730 PCIs were done during the initial hospital stay, and 928 after discharge. During the initial hospital stay, the median number of days before PCI was 6 days in both groups and 10 days overall. The average duration of follow-up after PCI was 8 months, also in both groups.

Baseline characteristics among patients assigned placebo

Discussion

Our study has shown that, in patients with acute coronary syndrome without ST-segment elevation undergoing PCI, clopidogrel reduces the risk of cardiovascular death or myocardial infarction by about a third, compared with placebo. This benefit was consistently seen in the period before PCI, in the 4 weeks after PCI (during which >80% of patients in both groups received open-label thienopyridine), and in the months thereafter when double-blind study medication was continued long-term. There was

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  • Cited by (0)

    For a full list of CURE Investigators, please see Eur Heart J 2000, 21: 2033–41. Study slides can be obtained at www.theCureStudy.com

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