American College of Cardiology (ACC) 2013 Scientific Sessions

March 9-13, 2013; San Francisco, CA

The High Cost of Major Bleeding in Patients With Nonvalvular Atrial Fibrillation

A retrospective analysis of healthcare claims for commercially insured and Medicare Advantage enrollees found that patients with nonvalvular atrial fibrillation who had major bleeding had substantially higher healthcare costs and more days in the hospital compared with those who had less severe bleeding. Results of the analysis were presented at the ACC meeting during a poster session.

Approximately 5 million adults in the United States have atrial fibrillation, a common cardiac rhythm disorder that is associated with a risk of bleeding, which can lead to higher costs, according to the authors. This study examined the Optum Research Database, which contains health plan member data, including enrollment information and inpatient, outpatient, and pharmacy claims. The authors obtained dates of death using the Social Security Death Master File.

Patients were included if they were 18 years of age or older and had two or more inpatient, emergency department, or ambulatory visits with a primary or secondary atrial fibrillation diagnosis on dates separated by at least 30 days between January 1, 2005 and June 30, 2009. They had to be continuously enrolled in the health plan for at least 1 year, and they could not have evidence of cardiac valvular disease. They were followed until they died, stopped enrollment in the plan, or made it to June 30, 2010—whichever time came first. The analysis included 48,260 patients. The mean age was 67.3 years, 71.2% of patients had commercial insurance, 62.2% were men, and 62.9% had hypertension. The mean length of follow-up was 802 days.

The authors found that 16,409 patients had a bleeding event. The mean cost for major bleeding events (n=6684) was $16,830, while the mean cost for serious nonmajor bleeding events (n=2017) was $1822, and the mean cost for minor bleeding events (n=7708) was $611. The mean duration for the events was 8 days: 15 days for major bleeding, 3 days for serious nonmajor bleeding, and 3 days for minor bleeding.

The mean daily cost for patients without bleeding was $33.67 compared with $48.28 for those who experienced bleeding. In the major bleeding group, the mean daily cost was $63.38 compared with $47.21 for those who had serious nonmajor bleeding and $37.96 for those with minor bleeding.

The mean duration of the postbleeding period was 523 days for patients with major bleeding, 583 days for patients with serious nonmajor bleeding, and 646 days for patients with minor bleeding. The authors noted a few limitations, including that the study relied on diagnostic codes from medical claims, which could have contained coding errors. They also noted that the results might be limited to patients with commercial or Medicare Advantage coverage and not to those with other types of coverage or the uninsured population. In addition, because the study was a descriptive, unadjusted cost analysis, patient factors other than bleeding events could have contributed to the high costs.—Tim Casey

This study was supported by Bristol-Myers Squibb and Pfizer Inc.

Ranolazine for Type 2 Diabetes, Coronary Artery Disease, and Chronic Stable Angina

Patients with type 2 diabetes, coronary artery disease, and chronic stable angina who took ranolazine had fewer angina episodes and fewer sublingual nitroglycerin dosages compared with a group receiving placebo, according to a randomized, double-blind, placebo-controlled study. Ranolazine is FDA-approved to treat chronic angina as a first-line therapy and as an add-on therapy when symptoms are not relieved using other antianginal drugs. Mikhail Kosiborod, MD, the study’s lead author, presented the data in a late-breaking clinical trial session at the ACC meeting. Results were simultaneously published online in the Journal of the American College of Cardiology (10.1016/j.jacc.2013.02.011).

Between weeks 2 and 8 of treatment, the mean angina frequency was 3.8 episodes per week in the ranolazine group compared with 4.3 episodes per week in the placebo group (P=.008). During that same time period, the mean number of sublingual nitroglycerin doses per week was 1.7 in the ranolazine group and 2.1 in the placebo group (P=.003). Kosiborod said 8 million people in the United States have angina, which is associated with a negative impact on health status and quality of life as well as repeat hospitalizations and high costs. He also said patients with diabetes are at an increased risk of coronary artery disease and have a greater angina burden.

The TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina) study recruited patients at 105 sites in 14 countries and was the first to test the antianginal effect of ranolazine in patients with diabetes. All patients had experienced symptoms despite receiving one or two antianginal medications. The authors collected data on angina frequency and sublingual nitroglycerin use on a daily basis using an electronic diary tool. During the study, 98% of patients added the data in their diary daily.

The trial began with a 4-week, single-blind, run-in phase during which all patients received placebo to establish the baseline angina frequency and to ensure patients were compliant with the study medication and with an electronic symptom diary, according to Kosiborod. The 949 patients were then randomized to receive 1000 mg ranolazine (n=473) or placebo (n=476) twice daily for 8 weeks.

The groups were well balanced at baseline. The mean age was approximately 64 years, 61% were men, and 99% were white. The mean duration of diabetes was approximately 7.5 years, the mean HbA_1c level was 7.3%, and 93% of patients were taking glucose-lowering medications. More than 80% of patients were taking concomitant statins or antiplatelet agents.

A subgroup analysis found that among patients recruited from Russia, Ukraine, and Belarus, there was no significant difference in mean angina frequency: 4.1 episodes per week in the ranolazine group and 4.3 episodes per week in the placebo group (P=.31). However, there was a significant difference among patients recruited from the other 11 countries, with patients taking ranolazine having a mean angina frequency of 3.1 episodes per week compared with 4.1 episodes per week in the placebo group (P=.002).

In addition, according to an exploratory, post hoc analysis, the benefit in angina frequency favoring ranolazine was significant in patients regardless of their HbA_1c level, although the drug’s effect was more profound in patients with a higher HbA_1c level at baseline. Further, there was no significant difference in serious adverse events, which occurred in 3.4% of patients in the ranolazine group and 4.2% of patients in the placebo group (P=.51). Kosiborod added nonserious adverse events, such as dizziness, nausea, and constipation, were more frequent in the ranolazine group, but they were “overall infrequent.”—Tim Casey

This study was funded by Gilead Sciences, Inc.