1 high clopidogrel loading dose is superior to a standard 300 mg regimen in patients undergoing...

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HIGH CLOPIDOGREL LOADING DOSE IS SUPERIOR HIGH CLOPIDOGREL LOADING DOSE IS SUPERIOR

TO A STANDARD 300 MG REGIMEN IN PATIENTS TO A STANDARD 300 MG REGIMEN IN PATIENTS

UNDERGOING PERCUTANEOUS CORONARY UNDERGOING PERCUTANEOUS CORONARY

INTERVENTION: EVIDENCE FROM A META-ANALYSISINTERVENTION: EVIDENCE FROM A META-ANALYSIS

G. BIONDI-ZOCCAI1, C. MORETTI1, P. AGOSTONI2, M. VALGIMIGLI3,

A. ABBATE4, D. ANGIOLILLO5, G. MONTALESCOT5,

G. SANGIORGI6, G. TREVI1 AND I. SHEIBAN1

1University of Turin, Turin, Italy; 2AZ Middelheim, Antwerp, Belgium;

3University of Ferrara, Ferrara, Italy; 4Virginia Commonwealth University, Virginia, USA;

5University of Florida, Jacksonville, Florida, USA; 6Hôpital Pitié-Salpétrière, Paris, France;

7Emo Centro Cuore Columbus, Milano, Italy

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BACKGROUND

• In patients undergoing intracoronary stenting, adjunctive treatment with clopidogrel in addition to aspirin is pivotal to minimize thrombotic occlusions and peri-procedural adverse events

• High loading dose regimens of clopidogrel (600 mg or more) lead to faster and enhanced platelet inhibition compared to standard dosing (300 mg) and may translate into improved clinical outcomes

• However, the clinical impact of high clopidogrel front-loading derives from small size trials and to date which is the best clopidogrel loading dose regimen is still a topic of debate

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OBJECTIVES

• To perform a systematic review to identify the optimal clopidogrel loading dose regimen in patients scheduled for coronary angiography and/or intervention

• To pool major outcomes with meta-analytic techniques

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METHODS

• Pertinent controlled trials were systematically searched in PubMed and other databases

• Authors of pertinent studies were systematically contacted

• The end-points were the rate of in-hospital myocardial infarction, and the 1-month rate of death or myocardial infarction

• Fixed-effect odds ratios (OR), 95% confidence intervals and p values were computed

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RESULTS

• A total of 10 studies (7 randomized, 3 non-randomized) were included, enrolling 1567 patients (712 loaded with 300 mg, 11 with 450 mg, 790 with 600 mg, and 54 with 900 mg)

• Overall a high loading dose proved significantly superior to a standard loading in preventing in-hospital myocardial infarction (OR=0.51 [0.26-0.99], p=0.05) and in preventing cardiac death or non-fatal myocardial infarction (OR=0.50 [0.30-0.84], p=0.009)

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RESULTS

• No significant increase in major or minor bleedings

(respectively p=0.55 and p=0.98) was found in patients

treated with a high clopidogrel dose

• Sensitivity analysis restricted to randomized trials

confirmed the superiority of a high loading dose regimen

on risk of death or infarction (p=0.001)

• Meta-regression disclosed a significant interaction

between event rate and benefits of high loading dose

(p=0.005), suggesting that the higher the underlying risk,

the greater the favorable impact of high loading

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REVIEW PROFILE

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INCLUDED STUDIES

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RISK OF D/MI AT 1 MONTH

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META-REGRESSION

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FUNNEL PLOT

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CONCLUSIONS

• Despite the inherent limitations of available evidence, a high clopidogrel loading dose regimen appears clinically and statistically superior to a standard (ie 300 mg) loading dose regimen in preventing coronary ischemic events

• Moreover, the greatest benefits can be expected in the highest risk subjects

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