Dr Shamir R Mehta MD a , Jean-Francois Tanguay MD b, John W Eikelboom MD a, Sanjit S Jolly MD a, Prof Campbell D Joyner MD c, Christopher B Granger MD d, Prof David P Faxon MD e, Hans-Jurgen Rupprecht MD f, Prof Andrzej Budaj MD g, Alvaro Avezum MD h, Prof Petr Widimsky MD i q, Prof Philippe Gabriel Steg MD j, Prof Jean-Pierre Bassand MD k, Gilles Montalescot MD l, Carlos Macaya MD m, Giuseppe Di Pasquale MD n, Kari Niemela MD r, Andrew E Ajani MD o, Prof Harvey D White MD p, Susan Chrolavicius BA a, Peggy Gao MSc a, Prof Keith AA Fox MBChB s, Prof Salim Yusuf MBBS a, on behalf of the CURRENT-OASIS 7 trial investigators‡. The Lancet, Early Online Publication, 1 September 2010
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.
Findings
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).
Interpretation
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.
Funding
Sanofi-Aventis and Bristol-Myers Squibb.
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