Authors
Mehta SR, Tanguay JF, Eikelboom JW, et al. CURRENT-OASIS 7 trial investigators.
Title
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
References
Lancet 2010;376:1233-43
Background
Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI).
Purpose
To assess whether doubling of the loading and maintenance dose of clopidogrel for 7 days was better than the standard dose, and whether high dose aspirin was better than low-dose aspirin in patients undergoing PCI
Design
International multicentre prospective randomized dose ranging trial double-blind for clopidogrel doses Pre-specified subgroup analysis of 17 263 individuals who underwent PCI for ACS Primary outcome: cardiovascular death, myocardial infarction, or stroke
Exclusion Criteria
Increased risk of bleeding or active bleeding.
Follow-Up
30 days
Treatment Regimen
Patients 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
Results
Primary Endpoints: Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome HR 0.86, 95% CI 0.74–0.99, p=0.039) 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). Secondary Endpoints: Compared with the standard dose, double-dose clopidogrel reduced the rate of definite stent thrombosis HR 0.54 [0.39–0.74], p=0.0001. Major bleeding was more common with double-dose than with standard-dose clopidogrel HR 1.41, 1.09–1.83, p=0.009) Major bleeding did not differ between high-dose and low-dose aspirin (HR 1.18, 0.92–1.53, p=0.20)
Summary
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, but a higher rate of bleeding was observed. Efficacy and safety did not differ between high-dose and low-dose aspirin.
Implications
At the price of an increased bleeding risk, a double-dose clopidogrel regimen for 7 days post angioplasty can reduce stent thrombosis and cardiovascular events. This evidence was adopted by some interventionists especially for patients who are believed to be at increased risk for early stent thrombosis, with a low bleeding risk.
Related Figures
None.