NEW YORK (Reuters Health) – As the number of prescribed antithrombotic drugs after a first myocardial infarction increases, so does the risk of hospitalization for bleeding, according to a report in the December 12th issue of The Lancet.

Therefore, before prescribing duel or triple-drug antithrombotic therapy, the researchers recommend a thorough risk/benefit assessment of each patient.

“Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after MI. However, data for the safety of the combinations are sparse,” Dr. Rikke Sorensen, from Copenhagen University Hospital Gentofte, Hellerup, Denmark, and colleagues note.

Using data from nationwide registers in Denmark, the authors identified 40,812 patients older than 30 years of age who were hospitalized for a first-time MI between 2000 and 2005. Discharge prescription data were analyzed and the subjects were categorized according to the antithrombotic agents given. These data were then correlated with records of hospital admission for bleeding.

During an average follow-up period of 476.5 days, 1,891 (4.6%) patients had a hospital admission for bleeding.

Among patients receiving a single agent, annual bleeding incidences were 2.6%, 4.6%, and 4.3% for aspirin, clopidogrel, and vitamin K antagonists, respectively. With drug combinations, the rates were typically higher, reaching a maximum of 12.3% when clopidogrel and a vitamin K antagonist were used together.

Compared with aspirin, the adjusted hazard ratios for bleeding were 1.23 for vitamin K antagonists, 1.33 for clopidogrel, 1.47 for aspirin plus clopidogrel, 1.84 for aspirin plus a vitamin K antagonist, 3.52 for clopidogrel plus a vitamin K antagonist, and 4.05 for triple therapy.

The rate of recurrent MI or death was also significantly higher in patients with non-fatal bleeding versus those without: 37.9% vs. 18.4% (HR 3.0, p < 0.0001).

“New stents, technologies, drugs, and perhaps assessments of platelet reactivity to tailor antiplatelet therapy to both ischemic and bleeding risk might lead to reduced risks of bleeding events in the future,” suggest editorialists Dr. Erik L. Grove, from Aarhus University Hospital, Skejby, Denmark, and Dr. Robert F. Storey, from the University of Sheffield, UK.

“However, balancing the risks and benefits of antiplatelet and anticoagulant treatment, including choosing the appropriate drugs and treatment duration, will remain a difficult clinical task,” they conclude.

Reference:
Lancet 2009;374:1947-1948,1967-1974.