Date Published: February 12, 2019
Publisher: Public Library of Science
Author(s): Aníbal García-Sempere, Isabel Hurtado, Daniel Bejarano-Quisoboni, Clara Rodríguez-Bernal, Yared Santa-Ana, Salvador Peiró, Gabriel Sanfélix-Gimeno, Nienke van Rein.
Worldwide, there is growing evidence that quality of international normalized ratio (INR) control in atrial fibrillation patients treated with Vitamin K Antagonists (VKA) is suboptimal. However, sex disparities in population-based real-world settings have been scarcely studied, as well as patterns of switching to second-line Non-VKA oral anticoagulants (NOAC). We aimed to assess the quality of INR control in atrial fibrillation patients treated with VKA in the region of Valencia, Spain, for the whole population and differencing by sex, and to identify factors associated with poor control. We also quantified switching to Non-VKA oral anticoagulants (NOAC) and we identified factors associated to switching.
This is a cross-sectional, population-based study. Information was obtained through linking different regional electronic databases. Outcome measures were Time in Therapeutic Range (TTR) and percentage of INR determinations in range (PINRR) in 2015, and percentage of switching to NOAC in 2016, for the whole population and stratified by sex.
We included 22,629 patients, 50.4% were women. Mean TTR was 62.3% for women and 63.7% for men, and PINNR was 58.3% for women and 60.1% for men (p<0.001). Considering the TTR<65% threshold, 53% of women and 49.3% of men had poor anticoagulation control (p<0.001). Women, long-term users antiplatelet users, and patients with comorbidities, visits to Emergency Department and use of alcohol were more likely to present poor INR control. 5.4% of poorly controlled patients during 2015 switched to a NOAC throughout 2016, with no sex differences. The quality of INR control of all AF patients treated with VKA in 2015 in our Southern European region was suboptimal, and women were at a higher risk of poor INR control. This reflects sex disparities in care, and programs for improving the quality of oral anticoagulation should incorporate the gender perspective. Clinical inertia may be lying behind the observed low rates of switching in patient with poor INR control.
Patients with atrial fibrillation (AF) are at an increased risk of stroke and thus require anticoagulant prophylaxis. For decades, treatment with vitamin K antagonists (VKA) has been the gold standard for stroke prevention in AF . The use of oral anticoagulants such as warfarin has been shown in clinical trials to reduce the risk of stroke by two thirds . However, the efficacy and safety of VKA are closely associated with the quality of anticoagulation control. Use of VKA can be challenging due to their narrow therapeutic range, as therapy must be tightly controlled and maintained within a therapeutic index of international normalized ratio (INR) values of between 2 and 3. Additionally, the need for periodic INR monitoring, high inter-patient variability in treatment response, numerous drug and food interactions and medication non-adherence are well-documented barriers to optimal INR control [3–9].
In this real-world, population-based study, we show that the quality of INR control in AF patients treated with VKA in 2015 in the region of Valencia is suboptimal, and that women are at a higher risk of uncontrolled INR. Depending on the definition used for acceptable INR ranges and TTR threshold, a quarter to two-thirds of patients had inadequate INR control during 2015. We also found that switching to NOAC in the following year was as low as 5.4% for patients with inadequate control and 4.1% for patients with adequate INR control. Importantly, women had a worse mean TTR, PINRR and poorer INR control than men, irrespective of definitions. In fact, being a woman, using VKA for more than 6 years and being at high risk were factors associated with poor INR control, while wealthier, older patients and those visiting a cardiologist or neurologist were more prone to good INR control. These figures are especially noticeable as VKA involve around two thirds of OAC treatments for AF patients and around 50% of new treatments .
This is the first study in our context to assess the quality of oral anticoagulation with VKA and switching to NOAC in AF patients on a population-basis using real-world data. The quality of INR control of all AF patients treated with VKA for stroke prevention in 2015 in our region was suboptimal, and women were at a higher risk of poor INR control. This reflects sex disparities in care, and programs for improving the quality of oral anticoagulation should incorporate the gender perspective at every step. In this sense, the approach used in our study with data from routine care could be incorporated into the EMR to improve patient follow-up. Observed low rates of switching in poor controlled patients is worrying, suggesting strong clinical inertia. Further studies should confirm our results, especially with regard to switching in new VKA users, and evaluate clinical outcomes associated with keeping patients with poor INR control on acenocoumarol.