Female Sex, Time in Therapeutic Range, and Clinical Outcomes in Atrial Fibrillation Patients Taking Warfarin

Abstract

Background and Purpose-Female patients have higher risk for stroke than male patients in nonanticoagulated atrial fibrillation patients, but limited data are available on sex differences in stroke and bleeding outcomes among patients with anticoagulated atrial fibrillation on warfarin, especially in relation to quality of anticoagulation control, as reflected by the time in therapeutic range (TTR). Methods-We investigated adverse outcomes in females (n=791) and males (n=1501) Table). Cardiovascular death rates were 1.2% and 1.8%/100 patients-years, and SSE rates were 2.0% and 1.0%/100 patients-years, respectively. No differences were seen between females versus males for the end points of cardiovascular death (P=0.24) and SSE (P=0.25). For bleeding outcomes, any clinically relevant bleeding occurred in 78 females (11.3%/100 patients-years) and 173 males (13.2%/100 patients-years; P=0.11). Major bleeding occurred in 8 females and 31 males (1.1% and 2.3%/100 patients-years, respectively). Females had a lower risk of major bleeding than males (P=0.02). Sex, Age, and TTRThere were no significant differences in mortality and stroke outcomes between females and males in the prespecified age subgroups. Figure I in the online-only Data Supplement shows that females age ≥75 had lower rate of any clinically relevant bleeding (adjusted P=0.04) and females age <75 had a lower rate of major bleeding (P=0.04) compared with males.TTR was negatively correlated with any clinically relevant bleeding in females(r=−0.86; P=0.03) and males (r=−0.94; P=0.005; Figure). Because of the low number of events, we were limited in power to detect differences between females and males for the TTR<65% and TTR≥65% subgroups; however, numerically lower clinically relevant bleeding events were seen in females compared with males (TTR<65%: females 13.7% versus males 15.7%; TTR≥65%: females 6.6% versus males 9.8%; P value for interaction=0.44). Multivariate AnalysisFor the end point of combined cardiovascular death/SSE events, independent predictors on Cox regression analysis were age (hazard ratio [HR] On logistic regression analysis, determinants of poor TTR (TTR<65%) were previous coronary artery disease in both Figure.Correlation and regression analysis between time in therapeutic range and incidence of any clinically relevant bleeding by sex. CV indicates cardiovascular; SE, systemic embolism; and SSE, stroke/systemic embolism.by guest on May 9, 2018

Dedicated warfarin care programme results in superior warfarin control in Queensland, Australia

“…Because of the retrospective nature of our study and access only to INR results prior to enrolment at the clinic, we were unable to measure outcomes in terms of adverse events and influence of interacting medications. However, TTR has been shown to be a good surrogate marker of outcomes with warfarin therapy, and enrolment in the dedicated warfarin clinic was shown to improve TTR even after only a six‐month period. This is likely to translate into improved outcomes from warfarin therapy but further investigation is required to confirm this improvement in terms of clinical efficacy and safety.…”

Use of D‐dimer in oral anticoagulation therapy

“…51 The low anticoagulant quality was correlated with the increase in risk of bleeding or thromboembolism. [52][53][54] Low TTR (<67%) was associated with the increase in D-dimer level. 55 Moreover, INR variation during the anticoagulation period (INR coefficient of variation, INR-CV%), which is another indicator of anticoagulation quality, was also a cause of the increase in D-dimer level.…”

Risk factors for severe bleeding events during warfarin treatment: the influence of sex, age, comorbidity and co-medication

“…There are several known risk factors for bleeding during treatment with oral anticoagulants, such as age, chronic comorbidities, prior bleeding and certain co-medications which are included in the HAS-BLED score [1]. Sex is not included in this risk score, and conflicting results have been found in different populations with several studies showing no difference in bleeding risk between the sexes [2][3][4][5][6][7], while other studies found a higher risk of bleeding in men [8][9][10][11]. To our knowledge, there is a lack of large population-based register studies on sex differences in severe bleeding risks in warfarin-treated patients.…”