Double-dose clopidogrel reduces risk of death, heart attack or stroke in patients undergoing angioplasty

September 01, 2010

An Article published Online First and in an upcoming Lancet (to coincide with the ongoing ESC meeting in Stockholm) shows that using a double-dose of the anticlotting treatment clopidogrel reduces the risk of cardiovascular death, heart attack, or stroke by 14% in patients undergoing angioplasty compared with normal dose. Although 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. Thus the authors, led by Dr. Shamir Mehta, Hamilton General Hospital and McMaster University, Hamilton, ON, Canada, conclude that double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy (also termed percutaneous coronary intervention or PCI).

Patients undergoing PCI are given standard anticlotting treatment consisting of aspirin and clopidogrel. In this study the authors assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis (narrowing of the inserted stent) in patients undergoing PCI.

8560 patients were assigned to double-dose and 8703 to standard-dose clopidogrel, and 8624 to high-dose and 8639 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 authors conclude: "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 ischaemic 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 linked Comment Dr Gregg Stone, Columbia University Medical Center and New York Presbyterian Hospital, NY, USA, points out that 30-day mortality was the same for both clopidogrel doses, and says: "Presumably, any benefits from reduced ischaemic complications in reducing mortality were offset by increased rates of major bleeding with double-dose clopidogrel. A reduction in major ischaemic 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 ischaemia versus bleeding."

He adds: "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."
Shamir R. Mehta, McMaster University, Hamilton, ON, Cananda. T) +1 905-531-3794 E)

Salim Yusuf, McMaster University. T) +1 905-527-4322 ext 40332 E)

John W. Eikelboom, McMaster University E)

Christopher B. Granger, Duke University. E)

Dr Gregg Stone, Columbia University Medical Center and New York Presbyterian Hospital, NY, USA. T) +1 646-434-4134 E)

For full Article and Comment, see:

Note to editors: *the embargo is mutually synchronised with publication of another study at the same time in the New England Journal of Medicine



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