In patients with myocardial infarction, risk of hospital admission for bleeding increases with the number of antithrombotic drugs used. Patients with non-fatal bleeding are also much more likely to suffer repeat myocardial infarction or die than those without this non-fatal bleeding.
Combinations of Acetylsalicylic acid ( Aspirin ), Clopidogrel ( Plavix ), and Vitamin K antagonists ( such as Warfarin [Coumadin ] ) are widely used in patients after a myocardial infarction. However, data on the safety of combinations are sparse. In this study, the authors examined the risk of hospital admission for bleeding associated with different antithrombotic regimens.
By use of nationwide registers from Denmark, the authors identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with Acetylsalicylic acid, Clopidogrel, or Vitamin K antagonist; dual therapy with Acetylsalicylic acid plus Clopidogrel, Acetylsalicylic acid plus Vitamin K antagonist, or Clopidogrel plus Vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were then assessed for each group.
During a mean follow-up of around 16 months, 1891 (4.6%) patients were admitted to hospital with bleeding or were diagnosed with a 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, and 12.0% for triple therapy.
With Acetylsalicylic acid as reference ( 1.0 ), increased risk of bleeding was 1.3 for Clopidogrel, 1.2 for Vitamin K antagonist, 1.5 for Acetylsalicylic acid plus Clopidogrel, 1.8 for Acetylsalicylic acid plus Vitamin K antagonist, 3.5 for Clopidogrel plus Vitamin K antagonist, and 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, NNH ) was 81 for Acetylsalicylic acid plus Clopidogrel, 45 for Acetylsalicylic acid plus Vitamin K antagonist, 15 for Clopidogrel plus Vitamin K antagonist, and 13 for triple therapy. 702 ( 38% ) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 ( 18% ) of 38,960 patients without non-fatal bleeding.
In conclusion, in patients with first-time myocardial infarction, all combinations of Acetylsalicylic acid, 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 Acetylsalicylic acid 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 myocardial infarction or death.
The Authors 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 riskbenefit ratio.
Source: The Lancet, 2010