An article in this week’s edition of The Lancet reports that the risk of hospital admission for bleeding in heart attack patients increases with the number of antithrombotic (clot-busting) drugs used. In addition, patients with non-fatal bleeding are also much more likely to suffer repeat heart attack or die than those without this non-fatal bleeding. The analysis of more than 40,000 Danish patients is documented in the article which is the work of Dr Rikke Sørensen, Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark, and colleagues.
After a heart attack, patients widely use combinations of aspirin, clopidogrel, and vitamin K antagonists such as warfarin. However, there is little information on the safety of combinations. The authors examined in this study the risk of hospital admission for bleeding associated with different antithrombotic regimens.
The authors identified 40,812 patients by using nationwide registers from Denmark. They were aged 30 years or older and had been admitted to hospital with first-time heart attack between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups:
• monotherapy with aspirin
• clopidogrel
• vitamin K antagonist
• dual therapy with aspirin plus clopidogrel
• aspirin plus vitamin K antagonist
• clopidogrel plus vitamin K antagonist
• triple therapy including all three drugs
Risk of hospital admission for bleeding, recurrent heart attack, and death were then evaluated for each group.
During a mean follow-up of around sixteen months, 1,891 (4•6 percent) patients were admitted to hospital with bleeding or were diagnosed with bleeding as the cause of death. The yearly incidence of bleeding was:
• 2•6% for the aspirin group
• 4•6% for clopidogrel
• 4•3% for vitamin K antagonist
• 3•7% for aspirin plus clopidogrel
• 5•1% for aspirin plus vitamin K antagonist
• 12•3% for clopidogrel plus vitamin K antagonist
• 12•0% for triple therapy
With aspirin as reference (1.0), increased risk of bleeding was:
• 1•3 for clopidogrel
• 1•2 for vitamin K antagonist (This particular finding was not statistically significant)
• 1•5 for aspirin plus clopidogrel
• 1•8 for aspirin plus vitamin K antagonist
• 3•5 for clopidogrel plus vitamin K antagonist
• 4•1 for triple therapy
The number of patients that needed to be treated in one year in order for one to be harmed, (the number needed to harm) was:
• 81 for aspirin plus clopidogrel
• 45 for aspirin plus vitamin K antagonist
• 15 for clopidogrel plus vitamin K antagonist
• 13 for triple therapy
A total of 702 (38 percent) of 1,852 patients with non-fatal bleeding had recurrent heart attack or died during the study period compared with 7,178 (18 percent) of 38, 960 patients without non-fatal bleeding.
The authors write in conclusion: “In patients with first-time heart attack, all combinations of aspirin, clopidogrel, and vitamin K antagonists are associated with increased risk of nonfatal and fatal bleeding, apart from monotherapy with a vitamin K antagonist, compared with aspirin alone. Increased risk of bleeding was proportional to the number of drugs used. Non-fatal bleeding is an independent predictor associated with increased risk of recurrent heart attack or death. We propose that treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment and careful consideration of the risk-benefit ratio.”
In an associated note, Dr Erik L Grove, Department of Cardiology, Aarhus University Hospital, Skejby, Denmark, and Dr Robert F Storey, Department of Cardiovascular Science, University of Sheffield, UK, remark: “The findings by Sørensen and colleagues suggest that a greater awareness of the prognostic importance of bleeding is warranted; they also underline the need for careful selection of antithrombotic drug combinations according to individual patient’s characteristics.”
“Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel,and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data”
Rikke Sørensen, Morten L Hansen, Steen Z Abildstrom, Anders Hvelplund, Charlotte Andersson, Casper Jørgensen, Jan K Madsen, Peter R Hansen, Lars Køber, Christian Torp-Pedersen, Gunnar H Gislason
Lancet 2009; 374: 1967-74
The Lancet
Written by Stephanie Brunner (B.A.)