Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

BACKGROUND: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. OBJECTIVE: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. METHODS: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. RESULTS: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). CONCLUSION AND RELEVANCE: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

Rivaroxaban Versus Warfarin for Stroke Prevention and Venous Thromboembolism Treatment in Extreme Obesity and High Body Weight.

Background: Limited clinical data exist describing the use of direct-acting oral anticoagulants (DOACs) in patients with body mass index (BMI) >40 kg/m2 or body weight >120 kg. Thus, DOAC therapy in this population remains controversial. Objectives: To investigate rivaroxaban as a safe and effective alternative to warfarin for venous thromboembolism (VTE) treatment and prevention of stroke in patients with atrial fibrillation identified as extremely obese or of high body weight. Methods: A retrospective chart review was performed at 2 academic medical centers in patients ≥18 years old and BMI >40 kg/m2 or weight >120 kg, newly initiated on warfarin or rivaroxaban for atrial fibrillation or VTE treatment. The primary end point was incidence of clinical failure, defined as VTE recurrence, stroke incidence, and mortality, within 12 months of initiation. Secondary end points included length of stay (LOS) and bleeding complications. Results: A total of 176 patients were included, with 84 and 92 patients in the rivaroxaban and warfarin arms, respectively. Clinical failure was lower in the rivaroxaban group but did not reach statistical significance when compared with warfarin (5% vs 13%; P = 0.06). LOS was significantly shorter in the rivaroxaban arm (2 days [1-3] vs 4 days [2-7], P < 0.0001). Percentage of bleeding complications was higher in the rivaroxaban arm but not statistically significant (8% vs 2%, P = 0.06). Conclusion and Relevance: Although not statistically significant, rivaroxaban trended toward a lower incidence of clinical failure while demonstrating a significantly shorter LOS when compared with warfarin for VTE treatment or atrial fibrillation in morbidly obese or high-body-weight patients.

Comparison of blood product use and costs with use of 3-factor versus 4-factor prothrombin complex concentrate for off-label indications.

PURPOSE: Results of a comparison of blood product use and cost outcomes with use of 3-factor versus 4-factor prothrombin complex concentrate (PCC) for indications other than warfarin reversal are presented. METHODS: Consecutive patients who received 3-factor PPC (PCC3) or 4-factor PCC (PCC4) for non-warfarin-related indications at 2 U.S. hospitals during a 19-month period were identified. The primary outcome was in-hospital blood product use, with a focus on plasma use. Total hemostasis costs, intensive care unit (ICU) and hospital lengths of stay, and other outcomes were evaluated. RESULTS: Indications for PCC3 use (n = 118) or PCC4 use (n = 64) included intraoperative bleeding, nonintraoperative bleeding, coagulopathy of liver disease, and reversal of direct-acting oral anticoagulant effects. The proportion of patients who received plasma was 56.8% with PCC3 use versus 53.1% with PCC4 use (p = 0.643); the corresponding median volumes of plasma received were 638 mL (interquartile range [IQR], 550-1,355 mL) and 656 mL (IQR, 532-1,136 mL), respectively. The median total hemostasis costs were $5,559 (IQR, $3,922-$8,159) with PCC3 use and $7,771 (IQR, $6,366-$9,205) with PCC4 use (p < 0.001). CONCLUSION: PCC3 use and PCC4 use were associated with similar blood product use, ICU length of stay, hospital length of stay, and in-hospital mortality when given for non-warfarin-related indications. However, relative to PCC3 use, PCC4 use was associated with an increase in costs that was primarily due to drug costs.

Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With Regard to Warfarin Reversal, Blood Product Use, and Costs.

BACKGROUND: Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. STUDY QUESTION: The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients. The secondary objectives include comparing blood product use, total reversal costs, and cost-effectiveness between the groups. STUDY DESIGN: This was a retrospective cohort study conducted in 2 affiliated, academic institutions in the United States. Consecutive adult patients who received 3-PCC or 4-PCC for warfarin reversal were included. MEASURES AND OUTCOMES: The primary outcome was adequate INR reversal defined as a final INR ≤1.5. Secondary outcomes were the utilization of plasma, red blood cells and platelets, reversal costs, and the cost-effectiveness ratio. RESULTS: There were 89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32). Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4-PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs. 47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4-PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033). CONCLUSIONS: Four-PCC was more effective than 3-PCC with regard to INR reversal in patients taking warfarin, but blood product use was similar. Although 4-PCC is associated with increased reversal costs, it may be cost-effective in terms of INR reversal.