Archief Roodbont

Additional antithrombotics increase bleeding risk in MI patients

11 December 2009

MedWire News: The risk for bleeding associated with antithrombotic treatment among myocardial infarction (MI) patients increases in proportion to the number of antithrombotic drugs used, report researchers in The Lancet.

Their analysis of data for over 40,000 patients hospitalized with MI in Demark showed that the relative risk for hospitalization for fatal and non-fatal bleeding increased with all drug combinations and with each additional drug used, although dual therapy with clopidogrel and a vitamin K antagonist was nearly as hazardous as triple therapy.

Rikke Sørensen and colleagues from Copenhagen University Hospital Gentofte, Denmark, and colleagues recommend triple therapy or dual therapy with clopidogrel and a vitamin K antagonist should only be prescribed after thorough individual patient risk assessment.

The researchers identified 40,812 patients aged 30 years or older who had been admitted to hospital with a first-time MI between 2000 and 2005. Claimed prescriptions starting at hospital discharge were analyzed to categorize patients according to use of aspirin, clopidogrel, or a vitamin K antagonist as monotherapy, or combinations of these drugs in dual or triple therapy.

During a mean follow-up of 476.5 days, 1852 (4.5%) patients were admitted to hospital with nonfatal bleeding, and 115 (0.3%) died from a bleeding event.

The unadjusted yearly incidence of non-fatal and fatal bleeding was 2.6% among patients who took aspirin only, 4.6% among those on clopidogrel, 4.3% for vitamin K antagonist monotherapy users, 3.7% for those taking the combination of aspirin and clopidogrel, 5.1% with aspirin plus vitamin K antagonist, 12.3% with clopidogrel plus vitamin K antagonist, and 12.0% with triple therapy.

Compared with aspirin monotherapy, all antithrombotic exposures except vitamin K antagonist monotherapy were associated with increased adjusted hazards for fatal and nonfatal bleeding.

“Increased risk was proportional to the number of drugs used,” the authors note.

The hazard ratios were 1.33 for clopidogrel, 1.23 for vitamin K antagonist, 1.47 for aspirin plus clopidogrel, 1.84 for aspirin plus vitamin K antagonist, 3.52 for clopidogrel plus vitamin K antagonist, and 4.05 for triple therapy.

Of note, non-fatal bleeding was associated with a significant three-fold increased hazard for MI or death (p<0.0001).

Erik Grove (Aarhus University Hospital, Denmark) and Robert Storey (University of Sheffield, UK) noted in an accompanying commentary that conclusions cannot be drawn as to whether this is a causal association, but that it ties in what has been seen in studies such as OASIS-5, in which a reduction in bleeding led to improved outcomes in terms of death, MI, and stroke.

The bleeding hazards associated with double and triple antithrombotic therapy are an increasingly important issue with the aging population, Grove and Storey said.

While new technologies, stents, and drugs and possibly individually tailored therapy based on platelet reactivity may help to reduce the risk for bleeding in the future, they added, “balancing the risks and benefits of antiplatelet and anticoagulant treatment… will remain a difficult clinical task.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

Lancet 2009; 374: 1967–1974