Major Bleeds With Warfarin in AF Are Often Fatal

November 27, 2012

TORONTO, Ontario — Results of a large observational study of warfarin use in AF patients suggest that major bleeding rates are higher than in clinical trials and are often fatal [1].

The authors, led by Tara Gomes (University of Toronto, ON), conclude that the study "provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients, and policy-makers as new options for treatment become available."

For the study, published online in CMAJ on November 26, 2012, Gomes and colleagues linked health administrative databases on prescription drugs and hospitalizations in Ontario. They identified 125 195 patients aged 66 years or over with AF who started warfarin between April 1997 and March 2008. Over the 13-year study period, the rate of major bleeding (defined as any visit to hospital for hemorrhage) was 3.8% per person-year.

Gomes told heartwire that these results were important, as "they reflect the bleeding rates with warfarin in the real world." She said the bleeding rate was "slightly higher than we expected, given that clinical trials have shown rates of major bleeding with warfarin between 1% and 3%."

Noting that some other observational studies have suggested higher bleeding rates than this, she pointed out that many of these studies had much shorter follow-up, and bleeding rates tend to be higher in the early treatment period. "We had a long follow-up period, and as time elapses patients tend to stabilize, so bleeding rates come down."

High Bleeding Rate in First Month

Indeed, this study also showed a higher bleeding rate at the start of treatment, with a major hemorrhage rate of 1% in the first 30 days, or 11.8% per person-year.

Another worrying finding was that, of the patients who were hospitalized for a bleed, 20% died in the hospital or shortly after discharge. Although the rate of intracranial hemorrhage was low in this study (0.2%), it was associated with a high mortality rate (42%).

As expected, bleeding rates were higher with increasing CHADS2 scores and with increasing age.

Rate of Hemorrhage, % Per Person-Year by CHADS2 Score

CHADS2 score Major bleed rate (% per person-year)
0 1.8
1 2.5
2–3 4.3
4–6 6.7

Rate of Hemorrhage, % Per Person-Year by Age

Age (y) Major bleed rate (% per person-year)
<75 or under 2.9
>75 4.6

The most common type of bleed necessitating hospitalization was gastrointestinal bleeding, which accounted for 62% of cases.

Gomes commented: "My message is that doctors should know the potential for bleeding in patients when starting them on warfarin. They should also recognize the symptoms of hemorrhage, such as blood in stools, and educate patients about this."

Asked whether this information would encourage more doctors to switch patients to one of the new oral anticoagulants, Gomes said she didn't think that decision could be made on the basis of these data. "Hemorrhage rates appear to be similar with the new drugs, but we haven't got enough real-world data available on them yet, and this study only looked at warfarin use."