OASIS-7 Trial Supports Double-Dose Clopidogrel Before PCI

September 1, 2010—A study by Shamir Mehta, MD, et al demonstrated that using a double-dose of clopidogrel reduces the risk of cardiovascular death, heart attack, or stroke by 14% compared with normal dose in patients undergoing angioplasty. Although the risk of major bleeding increased 40% with double-dosing, the risk of bleeding that was intracranial, fatal, or related to coronary artery bypass graft surgery did not increase. The study found that a double-dose clopidogrel regimen could be considered for all patients with acute coronary syndromes treated with percutaneous coronary intervention (PCI). The study was published online ahead of print in The Lancet and presented at the annual congress of the European Society of Cardiology in Stockholm.

In this study, the investigators assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI. The investigators assigned 8,560 patients to double-dose and 8,703 patients to standard-dose clopidogrel, and 8,624 patients to high-dose and 8,639 patients to low-dose aspirin. Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome of cardiovascular death, heart attack, or stroke (3.9% vs 4.5%; 14% reduced risk) and definite stent thrombosis (0.7% vs 1.3%; 46% reduced risk). High-dose and low-dose aspirin did not differ for the primary outcome (4.1% vs 4.2%). Major bleeding was more common with double-dose than with standard-dose clopidogrel (1.6% vs 1.1%; 41% increased risk) but did not differ significantly between high-dose and low-dose aspirin (1.5% vs 1.3%).



The investigators concluded, “In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose regimen of clopidogrel was more effective than was the standard dose regimen in reduction of ischemic events and stent thrombosis. Daily high-dose aspirin did not significantly differ from low-dose aspirin. A double-dose regimen of clopidogrel can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended PCI.”

In a related commentary in The Lancet, Gregg Stone, MD, noted that 30-day mortality was the same for both clopidogrel doses. Dr. Stone stated, “Presumably, any benefits from reduced ischemic complications in reducing mortality were offset by increased rates of major bleeding with double-dose clopidogrel. A reduction in major ischemic complications must be achieved without increasing overall bleeding, or vice versa, to further reduce mortality with antiplatelet and antithrombotic agents. The likelihood of achieving such a balance might be increased by considering individual patient's risks for ischemia versus bleeding.”

Dr. Stone added, “Further study is needed to establish whether clinical decision making can be improved with point-of-care platelet-function testing, by assessing the genetic potential for drug metabolism, or both.”