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

May 14, 2002
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Date Presented:
01/01/2001
Date Published:
01/01/2001
Date Updated:
05/14/2002
Original Posted Date:
05/14/2002
References

Description:

Post hoc analysis from the CURE trial of pretreatment and longterm therapy with clopidogrel vs. no pretreatment and 4 weeks of therapy with clopidogrel in patients undergoing PCI.

Hypothesis:

In addition to aspirin, pretreatment with clopidogrel before PCI would be superior to placebo in preventing major ischemic events after PCI. Long-term treatment with clopidogrel for up to 1 year after PCI would result in additional benefit.

Study Design

Study Design:

Patients Enrolled: 2658
Mean Follow Up: 8 months (mean)
Mean Patient Age: 61 (mean)
Female: 30

Patient Populations:

Patients with acute coronary syndromes hospitalized within 24 hours after the onset of symptoms and <1mm ST-segment elevation. Other electrocardiographic evidence of new ischaemia or concentrations of cardiac enzymes (including troponin) at least twice the upper limit of normal was required.

Exclusions:

1. Patients with contraindications to antithrombotic or antiplatelet therapy 2. Patients who were at high risk for bleeding 3 Patients with NYHA Class IV heart failure 3. Patients who were taking oral anticoagulants 4. Patients who had undergone coronary revascularization in the previous three months 5. Patients who had received intravenous glycoprotein IIb/IIIa receptor inhibitors in the previous three days.

Primary Endpoints:

The primary endpoints were a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularization within 30 days of PCI and cardiovascular death or myocardial infarction from the time of PCI to the scheduled end of the trial

Secondary Endpoints:

Major and minor bleeding

Drug/Procedures Used:

A 300 mg loading dose of clopidogrel or matching placebo was administered immediately after randomization, followed by 75 mg clopidogrel or matching placebo for 3 to 12 months (mean duration of treatment, 9 months). PCI was done after randomization at the discretion of the local investigator, and clopidogrel or placebo was continued up until this point. After PCI, stented patients received either clopidogrel or ticlopidine in combination with aspirin for 2-4 weeks. Subsequently, the randomly assigned study medication was resumed until the end of the scheduled follow-up.

Concomitant Medications:

Aspirin (recommended dose, 75 to 325 mg daily) was started or continued simultaneously with the study drug. Use of Glycoprotein IIb/IIIa receptor antagonists was discouraged and reserved for those with refractory ischemia, but these agents could be used during PCI.

Principal Findings:

Before PCI, significantly fewer patients on clopidogrel than on placebo had myocardial infarction or refractory ischemia (12·1% versus 15.3%; relative risk 0·76 [95% CI 0·62-0·93] p= 0·008). Patients underwent PCI at a mean 10 days after randomization. By 30 days after PCI, fewer patients in the clopidogrel group than the placebo group had a primary composite outcome of cardiovascular death, myocardial infarction, or urgent revascularization (4·5% vs. 6.4% realtive 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 the composite endpoint(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 a non-significant excess in major, but not life threatening, bleeding with clopidogrel compared with placebo.

Interpretation:

While provocative, it should be noted that this is a subgroup analysis from the larger CURE study. It should also be noted that only 30% of patients in the CURE trial eventually required an invasive strategy and only 6% of patients in the trial were treated with glycoprotein 2b3a inhibitors. Patients were not randomized to clopidogrel or placebo at the time of the PCI, but rather at the time of study entry. Patients underwent PCI a mean of 10 days after randomization, which is longer than the current waiting period in the US for patients with an acute coronary syndrome. This study was not designed to address the value of clopidogrel pretreatment in patients receiving up-front intravenous glycoprotein IIb/IIIa antagonists in the setting of PCI. Subanalysis of this trial suggests a complementary effect of Clopidogrel and glycoprotein 2b3a inhibitors, but randomized data are lacking.

References:

Mehta SR, Yusuf S, Peters RJ, Bertrand ME, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001 Aug 18;358(9281):527-33.

Keywords: Risk, Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Platelet Aggregation Inhibitors, Ticlopidine, Angioplasty, Balloon, Coronary, Purinergic P2Y Receptor Antagonists, Troponin


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