12/07/11

SEATTLE – A scoring system based on warfarin comorbidities and indications identifies patients at increased risk for warfarin adverse events, according to researchers from HealthCore Inc., the clinical outcomes research subsidiary of WellPoint Inc.

Analyzing the records of almost 16,000 WellPoint patients on warfarin, the researchers found that comorbidities such as cancer and chronic renal disease, and several indications for warfarin, including deep vein thrombosis, ischemic stroke, and heart valve replacement, increased the odds of warfarin-related hemorrhagic and thromboembolic events within the first 30 days of treatment.

The researchers added the odds ratios to develop adverse event propensity scores, and found that 5.9% of patients with scores of six or more had an adverse event within a month of starting warfarin. Just 1.4% of patients with scores below six had warfarin-related adverse events within the first month.

Patients with scores of six or greater were four times more likely to have an adverse event than were those with scores below six (95% CI 3.4-5.0, P = .0001).

The cut-score of six "was the point where we got reasonable gains without overdiagnosing. [The score identified] a population where the risk is actually quite high," Dr. Ralph Turner, MD, HealthCore senior research analyst, said at the annual research meeting of AcademyHealth.

"You don’t’ really make any gain" adding gender, age and other demographic variables to the model, he noted.

WellPoint is designing a pharmacist-outreach program to educate patients about warfarin and remind them to have their levels checked regularly; exceeding therapeutic ranges increases the risk of anticoagulation side effects.

The hope is to target limited outreach resources to patients most at risk for adverse events, which prompted HealthCore’s work, said pharmacist John Barron, PharmD, HealthCore’s executive director of health plan research.

"Even with close monitoring, you could still have an event, but it’s going to reduce the likelihood if you’re being monitored," he said.

The nearly 16,000 patients in the study were between 18 and 64 years old, and had no warfarin prescriptions in the previous 6 months.

Patients treated following heart valve replacements were most at risk for adverse events, with an odds ratio of 4.0. The adverse event odds ratio for treatment following transient ischemic attacks was 3.7; for deep vein thrombosis 3.4; and for ischemic stroke 2.5.

Among comorbid conditions, the highest adverse event odds ratio was in patients with chronic renal disease, at 1.7. Peripheral vascular disease’s odds ratio was 1.6; cancer’s 1.5; diabetes’ 1.3; and concomitant steroid use’s 1.5. The results were all statistically significant.

The researchers were surprised to find that patients anticoagulated following hip and knee replacements actually had a lower risk of warfarin adverse events than did those treated for other reasons. "We actually found a reduced risk in those folks," said Dr. Barron, though the reasons remain uncertain.

Dr. Barron and Dr. Turner said they have no disclosures. The study was funded by WellPoint.

M. Alexander Otto is a freelance writer based in Tacoma, Wash.