Major Bleeds on Warfarin More Likely as BMI Rises: Analysis

Marlene Busko

May 08, 2015

SAN FRANCISCO, CA — In a small, 1-year study of patients receiving warfarin, obese patients had an 84% greater risk than nonobese patients of developing a major bleed that required hospitalization[1].

Moreover, the risk of major bleeding increased stepwise in three levels of obesity, Dr Adedotun A Ogunsua (University of Massachusetts Medical School, Worcester, MA) and colleagues report in a poster presented at the Arteriosclerosis, Thrombosis and Vascular Biology/ Peripheral Vascular Disease 2015 Scientific Sessions .

This single-center, retrospective study showed that "there is a tendency for patients who are obese to bleed while on Coumadin, because they require a higher dose and a longer time to become therapeutic on that dose," Ogunsua told heartwire from Medscape. However, this was a preliminary observational study, he cautioned, and it may not have controlled for all confounders.

Nevertheless, the results suggest that body-mass index (BMI) may predict bleeding events in patients on warfarin. "Future studies are needed to understand the mechanism by which obesity increases bleeding risk for patients on warfarin and whether similar risks exist for the novel oral anticoagulants," Ogunsua and colleagues conclude.

Higher Warfarin Dose in Obesity, Higher Bleeding Risk?

Warfarin is commonly given to obese (and other) patients to prevent cerebrovascular events in atrial fibrillation, to treat or prevent deep venous thrombosis (DVT) and pulmonary embolism (PE), and to lower the risk of blood clots after cardiac-valve replacement, the authors write. However, the optimal dosing for obese patients is unknown, although it takes longer to obtain a therapeutic INR when warfarin is started, and obese patients require a higher maintenance dose.

Moreover, few studies have examined the relationship between warfarin and bleeding events in obese patients. To examine this, Ogunsua and colleagues reviewed data from 863 patients on warfarin therapy who were seen in their medical center's anticoagulation clinic from March 2013 until April 2014. The patients had a mean age of 71 years, and 46.5% were female.

About 60% of the patients were of normal weight (BMI 18.5–24.99; 21% of patients) or overweight (BMI 25–29.99; 38%). The rest were obese class I (BMI 30–34.99; 21%), obese class II (BMI 35–39.99; 9%) or obese class III (BMI >40; 11.3%).

Most patients (60.6%) had a CHA2DS2-VAScscore >4, and about a third had a CHA2DS2-VASc score of 3, while the rest had a lower score. Slightly more than a quarter of the patients (28%) had heart failure, and a similar number (29.6%) had diabetes; about three-quarters had hypertension.

The patients were receiving warfarin for a variety of reasons: 18.3% had nonvalvular atrial fibrillation; 11.3% had a mechanical valve; 26.8% had DVT; and 14% had PE.

During the 1-year study, 71 patients (8.2%) had a bleeding event. Of these, 38 patients (4.4%) had major bleeds that required hospitalization: gastrointestinal bleeding from any source with or without a transfusion, and retroperitoneal or intracranial bleeding warranting discontinuation of warfarin treatment. The other 33 patients (3.8%) had a nonmajor bleed: epistaxis, hematuria, or vaginal and skin bleeds. Only the index bleeds were considered.

In univariate analysis, the risk for bleeding increased with increasing obesity categories.

Risk of a Major Bleeding Event, Obese Categories vs Nonobese*

Obesity Class BMI HR (95% CI) P
I 30–34.99 1.30 (0.75–2.5) 0.39
II 35–39.99 1.85 (0.7–4.6) 0.19
III > 40 1.93 (0.9–4.2) 0.09
Nonobese: BMI<30

After adjustment for multiple confounders—age>65 years, Hispanic ethnicity, sex, smoking, alcohol, congestive heart failure, dual antiplatelet therapy (aspirin and clopidogrel), and serum albumin—obesity (BMI >30) was associated with a significantly increased risk of a major bleed (HR 1.84, 95%CI, 1.33–2.55; P<0.001).

"When making a decision to put a patient on anticoagulation, we need to employ clinical decision-making tools to [weigh the risks and benefits and to] inform the patient that 'these are the risks, and the fact that you're obese might put you at a higher risk of bleeding,' " Ogunsua said. "Bleeding, in most situations, we can control, but stroke usually leads to a lot of deficits that some patients are not willing to tolerate," he noted.

The authors have no relevant financial relationships.

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