Warfarin tablets

Dabigatran poses a greater risk of major bleeding and gastrointestinal (GI) bleeding compared to warfarin, according to a study of patients with atrial fibrillation.

The incidence of GI and major bleeding with dabigatran was particularly high in African Americans, patients with chronic kidney disease (CKD), patients age 75

and older, and those with 7 or more comorbidities.

On the other hand, the risk of intracranial hemorrhage was higher in most warfarin-treated patients. African Americans were the exception to this rule.

Researchers reported these results in JAMA Internal Medicine alongside a related editorial.

“Dabigatran was introduced in 2010 and, at the time of approval, it was the only available alternative to warfarin,” noted study author Yuting Zhang, PhD, of the University of Pittsburgh in Pennsylvania.

“Warfarin dosing can be tricky, and regular monitoring with blood tests is required, so doctors and patients were glad to have a drug that was easier to manage. But some recent studies suggest that dabigatran is associated with a higher risk of bleeding.”

To investigate that possibility, Dr Zhang and her colleagues reviewed pharmacy and medical claims data from 2010 and 2011 of a random national sample of Medicare beneficiaries. The team tracked 1302 dabigatran users and 8102 warfarin users to see whether they experienced bleeding episodes.

The researchers classified bleeding events as major, such as intracranial bleeding or GI bleeding requiring a hospital or emergency room stay, or minor, such as GI bleeding that was treated on an outpatient basis or nose bleeds.

The incidence of any bleeding was significantly higher in dabigatran-treated patients than in warfarin-treated patients (32.7% vs 26.5%, P<0.001). The same was true of major bleeding (9% vs 5.9%, P<0.001) and GI bleeding (17.4% vs 10%, P<0.001).

However, the rate of intracranial bleeding was higher with warfarin than with dabigatran (1.8% vs 0.6%, P<0.001), as was the rate of epistaxis (3.1% vs 2%, P=0.002) and not-otherwise-specified hemorrhage (5.9% vs 4.4%, P=0.003).

All other types of bleeding were more frequent in the dabigatran group than the warfarin group. This included hematuria (12% vs 8.8%, P<0.001), vaginal bleeding (0.7% vs 0.3%, P=0.003), hemarthrosis (0.5% vs 0.2%, P=0.007), and hemoptysis (2% vs 1.4%, P=0.03).

The researchers also looked at bleeding episodes in 4 high-risk subgroups: patients who were 75 years of age and older, African Americans, patients with CKD, and those with 7 or more co-existing medical problems.

The risk of major bleeding was higher among dabigatran-treated patients belonging to these subgroups. The hazard ratios (HRs) were 1.60 for patients 75 and older, 2.12 for African Americans, 2.07 for patients with CKD, and 1.88 for patients with 7 or more comorbidities.

Likewise, the risk of GI bleeding was higher among dabigatran-treated patients in the subgroups. The HRs were 1.85 for patients 75 and older, 2.38 for African Americans, 1.81 for patients with CKD, and 1.81 for patients with 7 or more comorbidities.

“These findings indicate that physicians should be cautious when prescribing dabigatran, particularly to African Americans and patients with kidney impairments,” said study author Inmaculada Hernandez, PharmD, of the University of Pittsburgh.

“Also, the incidence of gastrointestinal bleeding was high in all the subgroups, so we recommend doctors explain to patients how to detect it so that it can be treated promptly.”

The researchers also noted that the risk of intracranial bleeding varied among the subgroups. The HRs for dabigatran vs warfarin were 0.10 for patients 75 and older, 2.29 for African Americans, 0.71 for patients with CKD, and 0.59 for patients with 7 or more comorbidities.

“We plan to examine 2012 data to monitor the risk of stroke for patients on dabigatran, which is the primary indication for taking the blood thinner,” Dr Zhang said. “It’s possible that, for some patients, a greater reduction in the risk of stroke will outweigh the higher risk of bleeding with dabigatran compared to warfarin.”

Dabigatran increases major, GI bleeding in AF