Time in therapeutic range is lower in women than in men and is not explained by differences in age or comorbidity

Background: Time in therapeutic range (TTR) measures the stability of the international normalized ratio in patients on vitamin K antagonists (VKA). Low values are associated with poor outcomes. Women were shown to have lower TTR than men, but the causes are poorly defined. It was suggested that women on VKA are older and more morbid than men, and this could affect the stability of anticoagulation. We aimed to identify variables that affect TTR differently in women and men. Materials and methods: This is a retrospective study in patients referred to a University hospital anticoagulant clinic. Age, sex, comorbidities, number of daily medications, indication and type of anticoagulant, weekly dosage and distribution, were derived from electronic records. Differences by sex and regression analysis to identify significant modulators of TTR were computed. Results: 1182 women and 1281 men on VKA were studied. Women were older than men (81.5 yrs. ± 11.2 vs 78.4 yrs. ± 12.2), and had lower TTR (65% ± 20.3 vs 69% ± 19.8). Comorbidity was similar between sexes and negatively affected TTR in both. Mechanical valves as an indication to anticoagulation and acenocoumarol as an anticoagulant as opposed to warfarin had a strong negative influence on TTR, while age increased TTR. Being a man rather than a woman afforded more than three TTR points. Number of medications and average anticoagulant dose were equal between sexes. Discussion: Women have a lower TTR than men, on average below the safety threshold. They were indeed older, but age positively influenced TTR. Since women and men were equally comorbid, neither age nor disease explains differences in TTR. None of the other variables included in the study could explain the gender gap in TTR. Since women are at increased risk of cardioembolic stroke in atrial fibrillation, an effort at defining other causes for the observed differences, closer monitoring and switching to direct anticoagulants whenever possible is warranted.