FDA Investigation Finds No Excess Bleeding Risk For Dabigatran 1

In its latest assessment of a highly controversial issue, the FDA has found no indication that bleeding rates for dabigatran (Pradaxa, Boehringer-Ingelheim) are any higher than the bleeding rates for warfarin. The FDA investigation was in response to the large number of post-marketing reports of bleeding in people taking dabigatran. Click here to for the full FDA statement. Here is the first paragraph of the statement:

The U.S. Food and Drug Administration (FDA) has evaluated new information about the risk of serious bleeding associated with use of the anticoagulants (blood thinners) dabigatran (Pradaxa) and warfarin (Coumadin, Jantoven, and generics). Following the approval of Pradaxa, FDA received a large number of post-marketing reports of bleeding among Pradaxa users.  As a result, FDA investigated the actual rates of gastrointestinal bleeding (occurring in the stomach and intestines) and intracranial hemorrhage (a type of bleeding in the brain) for new users of Pradaxa compared to new users of warfarin.  This assessment was done using insurance claims and administrative data from FDA’s Mini-Sentinel pilot of the Sentinel Initiative. The results of this Mini-Sentinel assessment indicate that bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin, which is consistent with observations from the large clinical trial used to approve Pradaxa (the RE-LY trial).1 (see Data Summary). FDA is continuing to evaluate multiple sources of data in the ongoing safety review of this issue.

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Real World Bleeding Risk Of Aspirin In Primary Prevention Examined Reply

A new study published in JAMA provides substantial new evidence about the real world effects of aspirin, including the risk of  bleeding, in a broad  population. The study also sheds important new light on the effects of aspirin in a diabetic population.

Giorgia De Berardis and colleagues analyzed data from more than 4 million people in Puglia, Italy and compared 186,425 people taking low-dose aspirin with the same number of matched controls not taking aspirin.

Major bleeding events requiring hospitalization:

  • aspirin: 5.58 (5.39-5.77) per 1000 person-years
  • controls: 3.60 ( 3.48-3.72) per 1000 person-years
  • Incidence rate ratio (IRR) 1.55 (1.48-1.63)

Diabetics overall had an increased risk of major bleeding episodes but this increased risk was not significantly associated with aspirin use:

  • Hemorrhagic events in diabetics overall (compared with non diabetics): IRR 1.36 (1.28-1.44)
  • Hemorrhagic events in diabetics taking aspirin compared with diabetics not taking aspirin: IRR 1.09 (0.97-1.22)

The authors wrote that their findings demonstrate that bleeding events occur more frequently than had been observed in clinical trials. They calculated that for individuals with a 10-year risk of cardiovascular events between 10% and 20% the risks and benefits of aspirin therapy are similar, causing 2 excess bleeds, and preventing 2 CV events, for every 1,000 people treated each year.

In an accompanying editorial, Jolanta Siller-Matula writes that the benefits of aspirin in secondary prevention are “not disputed,” since aspirin can prevent 6 major vascular events at the expense of 1 major bleeding event. But there is no such consensus for primary prevention, and Siller-Matula writes that the findings of the Italian study reinforce current European guidelines which do not recommend aspirin for primary prevention.

The JAMA study provides far more information about aspirin use in diabetics than had been previously available. Nevertheless, writes Siller-Matural, the decision whether to use aspirin for primary prevention in this population is still not clear, and will require additional data from ongoing studies.

Click here to read the JAMA press release…