PCI-CLARITY (Percutaneous Coronary Intervention-Clopidogrel as Adjunctive Reperfusion Therapy)

18 Mar, 14

Objective

To determine if clopidogrel pretreatment before PCI in patients with recent ST-segment elevation myocardial infarction (STEMI) is superior to clopidogrel treatment initiated at the time of PCI in preventing major adverse cardiovascular events.

Study Design and Participants

Prospectively planned analysis of the 1863 patients undergoing PCI after mandated angiography in CLARITY-Thrombolysis in Myocardial Infarction (TIMI) 28, a randomized, double-blind, placebo-controlled trial of clopidogrel in patients receiving fibrinolytics for STEMI

Interventions

Patients received aspirin and were randomized to receive either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo initiated with fibrinolysis and given until coronary angiography, which was performed 2 to 8 days after initiation of the study drug

For all patients undergoing coronary stenting, an open label clopidogrel therapy (300 mg loading dose followed with 75 mg once daily) was administered after the diagnostic angiogram

Outcome Measures

Primary outcome was the incidence of the composite of cardiovascular death, recurrent MI, or stroke from PCI to 30 days after randomization

Secondary outcomes included recurrent MI or stroke before PCI and the composite of cardiovascular death, recurrent MI, or stroke from randomization to 30 days

Primary Safety Outcome

Primary safety outcome was the rate of TIMI major or minor bleeding from PCI to 30 days after randomization.

Results

Pretreatment with clopidogrel reduced the rate of recurrent MI or stroke before PCI by 38%
Pretreatment with clopidogrel before PCI significantly reduced by 46% the odds of cardiovascular death, recurrent MI, or stroke within 30 days following PCI

Figure 1. Incidence of Cardiovascular End Points Before and After PCI

Benefits of pretreatment were independent of patient age and sex, presence of diabetes mellitus, infarct location, urgent or elective PCI, timing of PCI relative to randomization, predominant type of heparin used and whether GP IIb-IIIa inhibitor or open label clopidogrel was given at the time of PCI

Safety

There was no significant excess in the rates of TIMI major bleeding, TIMI minor bleeding, or the combination following PCI

Table 1. Safety Outcomes

Among patients who received a GP IIb-IIIa inhibitor during PCI, the rate of TIMI major or minor bleeding was not higher in clopidogrel pretreatment group (2.1%) than in those who did not receive pretreatment (2.9%) (P=.36)

Implications for Clinical Practice

Only 23 patients would need to be pretreated with clopidogrel to prevent 1 cardiovascular death, MI, or stroke.

In 100 patients, 4 major cardiovascular events can be avoided simply by the use of 1 to 3 doses of clopidogrel before PCI.

Conclusions

In high-risk STEMI patients treated with fibrinolytic therapy, clopidogrel pretreatment significantly reduces the incidence of cardiovascular death and ischemic complications both before and after PCI without a significant increase in major or minor bleeding

These data add further support to the early use of clopidogrel in STEMI and the broader strategy of clopidogrel pretreatment in patients undergoing PCI.

JAMA 2005;294:1224-32