Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial.
BACKGROUND
Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI.


METHODS
The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries. 25,086 individuals with acute coronary syndromes and intended early PCI were randomly assigned to double-dose (600 mg on day 1, 150 mg on days 2-7, then 75 mg daily) versus standard-dose (300 mg on day 1 then 75 mg daily) clopidogrel, and high-dose (300-325 mg daily) versus low-dose (75-100 mg daily) aspirin. Randomisation was done with a 24 h computerised central automated voice response system. The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes. This prespecified analysis is of the 17,263 individuals who underwent PCI. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Analyses were by intention to treat, adjusted for propensity to undergo PCI. This trial is registered with ClinicalTrials.gov, number NCT00335452.


RESULTS
8560 patients were assigned to double-dose and 8703 to standard-dose clopidogrel (8558 and 8702 completed 30-day follow-up, respectively), and 8624 to high-dose and 8639 to low-dose aspirin (8622 and 8638 completed 30-day follow-up, respectively). Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome (330 events [3·9%] vs 392 events [4·5%]; adjusted hazard ratio 0·86, 95% CI 0·74-0·99, p=0·039) and definite stent thrombosis (58 [0·7%] vs 111 [1·3%]; 0·54 [0·39-0·74], p=0·0001). High-dose and low-dose aspirin did not differ for the primary outcome (356 [4·1%] vs 366 [4·2%]; 0·98, 0·84-1·13, p=0·76). Major bleeding was more common with double-dose than with standard-dose clopidogrel (139 [1·6%] vs 99 [1·1%]; 1·41, 1·09-1·83, p=0·009) and did not differ between high-dose and low-dose aspirin (128 [1·5%] vs 110 [1·3%]; 1·18, 0·92-1·53, p=0·20).


CONCLUSIONS
In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the standard dose. Efficacy and safety did not differ between high-dose and low-dose aspirin. A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI.


BACKGROUND
Sanofi-Aventis and Bristol-Myers Squibb.
Mehta
Shamir R
SR
McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada. smehta@mcmaster.ca
Tanguay
Jean-Francois
JF
Eikelboom
John W
JW
Jolly
Sanjit S
SS
Joyner
Campbell D
CD
Granger
Christopher B
CB
Faxon
David P
DP
Rupprecht
Hans-Jurgen
HJ
Budaj
Andrzej
A
Avezum
Alvaro
A
Widimsky
Petr
P
Steg
Philippe Gabriel
PG
Bassand
Jean-Pierre
JP
Montalescot
Gilles
G
Macaya
Carlos
C
Di Pasquale
Giuseppe
G
Niemela
Kari
K
Ajani
Andrew E
AE
White
Harvey D
HD
Chrolavicius
Susan
S
Gao
Peggy
P
Fox
Keith A A
KA
Yusuf
Salim
S
D054058:Acute Coronary Syndrome / Q000628:therapy*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin