The safety of multiple antithrombotic drug regimes has not been investigated in clinical trials.  Specifically, guidelines for the management of patients with myocardial infarction who also have an indication for warfarin are currently unclear; some recommend the use of clopidogrel and warfarin in combination following coronary stent implantation.  As bleeding episodes following myocardial infarction are associated with increased morbidity and mortality, the use of undocumented treatment combinations raises concerns.

Sorensen and colleagues used nationwide registers from Denmark to identify 40812 patients who had been admitted to hospital with first time myocardial infarction (MI) between 2000 and 2005.  The authors examined the prescriptions started at discharge to divide the patients in to groups of: monotherapy with aspirin, clopidogrel, or warfarin; dual therapy with any two of the preceeding agents; or triple therapy.  The risk of hospital admission for bleeding, recurrent MI, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates.  The main results are summarised in table 1.

Table 1: Risk of bleeding following myocardial infarction according to antithrombotic agents given

http://heart.bmj.com/site/misc/March1.pdf

Conclusions:
Following myocardial infarction, the risk of hospital admission for bleeding increases with the number of antithrombotic drugs used.  The highest risk is seen with triple therapy or the use of clopidogrel and vitamin K antagonists;  this combination should only be prescribed on a case-by-case basis.

•    Sorensen R, Hansen ML, Abildstrom SZ et al.  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.  Lancet 2009:374;1967-1974.