Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR

Abstract

High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

Clinical usefulness of the SAMe-TT2R2 score: A systematic review and simulation meta-analysis

“…Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic INR range (iTTR) [ 1 ] and low INR variability [ 2 , 3 ]. The SAMe-TT 2 R 2 score [ 8 ] was developed to identify VKA control outliers before they started treatment.…”

Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing

“…The TTR (which is also included in the HAS-BLED score) was lower in patients with bleeding. It is known that patients with a low TTR are at higher risk of complications (either bleeding or thrombosis) [30]. A significantly higher HAS-BLED score was detected in patients with bleeding events compared to those without.…”

Improved Outcomes by Integrated Care of Anticoagulated Patients with Atrial Fibrillation Using the Simple ABC (Atrial Fibrillation Better Care) Pathway

“…warfarin) significantly reduces stroke and systemic thromboembolism (by 64%) and all-cause mortality (by 26%) when compared to placebo or control 14 . If VKAs are used, attention to quality of anticoagulation control, as expressed by TTR, is crucial as TTR is a major determinant of major adverse outcomes [15][16][17][18][19] . In the AFFIRM trial, the only OAC used was warfarin, and a high TTR has been associated with improved outcomes 15,20 .…”