PCC for warfarin reversal does not reduce mortality compared to FFP

Anna Garrett

Prothrombin complex concentrates (PCC) can rapidly normalize an elevated international normalized ratio [INR] in patients who become supratherapeutic on warfarin. Investigators recently conducted a retrospective study to determine whether reversal of warfarin coagulopathy with 4-factor PCC improves the survival of patients with VKA-related intracerebral hemorrhage as compared to plasma.

They included 135 patients treated with either plasma or 4-factor PCC for the reversal of their coagulopathy. Patients who received plasma (n=35, median 4 units) more often had diabetes, antiplatelet therapy, and intraventricular hemorrhage on the initial CT scans than did patients who received PCC (n=100, median dose=22.5 IU/kg) Hematomas were larger in the plasma-treated group vs. the PCC-treated group. The unadjusted odds for all-cause 30-day mortality in the PCC group were 0.40 compared to those of the plasma group. After adjusting for the hematoma volume, bleeding localization, and age, the effect of PCC on mortality was non-significant. The authors concluded that compared to plasma, treatment with 4-factor PCC for warfarin reversal in patients with intracerebral hemorrhage does not seem to reduce 30-day all-cause mortality.

Source: Majeed A, Meijer K, Larrazabal R et al. Mortality in vitamin K antagonist-related intracerebral bleeding treated with plasma or 4-factor prothrombin complex concentrate. Thromb Haemost 2014; 29;111(2):233–239.

Simple scoring system may identify patients at risk of poor INR control with warfarin

When oral anticoagulation with adjusted-dose warfarin is used, the quality of anticoagulation control (as reflected by the time in therapeutic range [TTR] of the INR) is an important determinant of thromboembolism and bleeding. A group of researchers created a validated tool using patient-related clinical parameters to assess the likelihood of poor INR control among patients with atrial fibrillation (AF) on VKA therapy.

In the data they collected, nine variables emerged as independent predictors of TTR: female sex, age <50 years, age 50 to 60 years, ethnic minority status, smoking, more than two comorbidities, and being treated with a β-blocker, verapamil, or amiodarone. The authors then incorporated these factors into a simple clinical prediction model with the acronym SAMe-TT2R (sex female, age <60 years, medical history [more than two comorbidities], treatment [interacting drugs, e.g., amiodarone for rhythm control], tobacco use, and race).  

These findings are important because clinicians can use the scoring information to predict potential problems with INR control in certain patients. This may prompt the prescriber to consider use of a novel anticoagulant or provide additional patient support to improve TTR.

Source: Apostolakis S, Sullivan R, Oshansky B et al. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: The SAMe-TT2R2 score. Chest 2013;144(5):1555–1563.

Edoxaban demonstrates positive outcomes in AF

Edoxaban is an investigational direct oral factor Xa inhibitor with proven antithrombotic effects. A recently published study of patients with atrial fibrillation demonstrated positive outcomes in this patient population when edoxaban was compared to warfarin.

The trial, which included 21,105 patients with moderate-to-high-risk atrial fibrillation, tested two once-daily dosing regimens of edoxaban against dose-adjusted warfarin (INR 2-3). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding.

The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban and 1.61% with low-dose edoxaban. The annualized rate of major bleeding was 3.43% with warfarin vs. 2.75% with high-dose edoxaban and 1.61% with low-dose edoxaban. The corresponding annualized rates of death from cardiovascular causes were 3.17% for warfarin vs. 2.74% and 2.71% respectively for high- and low-dose edoxaban.

Daiichi-Sankyo recently applied for FDA approval of edoxaban. The brand name will be Savayasa.

Source: Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban vs. warfarin in patients with atrial fibrillation. N Engl J Med 2013;369(22):2093–2104.

Anna D. Garrett is a clinical pharmacist and president of Dr. Anna Garrett (www.drannagarrett.com). Her mission is to help women in midlife maximize their mojo! Contact her at info@drannagarrett.com.