1

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

2

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

3

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

4

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

5

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)

6

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

7

REVIEW PROFILE

8

INCLUDED STUDIES

9

RISK OF D/MI AT 1 MONTH

10

META-REGRESSION

11

FUNNEL PLOT

12

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

For further slides on these topics For further slides on these topics please feel free to visit the please feel free to visit the

metcardio.org website:metcardio.org website:

http://www.http://www.metcardiometcardio..orgorg//slidesslides..htmlhtml