ABC | Volume 114, Nº3, March 2020

Original Article Silva et al. Warfarin therapy in NVAF patients in Brazil Arq Bras Cardiol. 2020; 114(3):457-466 Figure 1 – Flow chart describing inclusion and exclusion criteria. Patients with diagnosis of atrial fibrilation with at least one warfarin claim and available INR results. n = 2,122 Excluded (n = 902) due to evidence of moderate/severe mitral stenosis, mechanical prosthetic valve, VTE, followed for less than 4 months with record of the calls in less than 50% of the months. Patients included in the main analysis n = 1,220 Excluded (n = 286) followed for less than 6 months. Patients included in the sensitivity analysis n = 934 in this patient group. The median and mean patient‑level TTRs were almost the same, 57% (IQR 45%–68%) and 58% ± 16.2%, respectively. In this group of patients, PMPY costs, including inpatient and outpatient, were also quite similar, R$31,229 (USD$10,331), versus R$32,284 (USD$10,680) for the main analysis. Discussion Overall, it was observed that the quality of anticoagulation management was suboptimal: only half of all INR values drawn were in the therapeutic range (INR: 2-3) and patients spent a bit more than half of the time within the therapeutic range. TTR varied across the population and up to two thirds of patients were not adequately controlled (TTR < 65%). These patients were associated with more unfavorable clinical and economic outcomes i.e. more major bleeds and higher costs. Epidemiological data suggest that there were over 700,000 strokes in Brazil in 2010, accounting for over 141,000 deaths. 18 While there are several underlying causes of stroke, it is estimated that approximately 20% of ischemic strokes are attributable to atrial fibrillation, 19 and strokes associated with atrial fibrillation tend to be larger and associated with worse outcomes. 20 Anticoagulation therapy has the potential to greatly reduce the risk of stroke in patients with atrial fibrillation. Warfarin has been shown to reduce the risk of ischemic stroke by 64% and mortality by 26% but the usefulness of warfarin is variable due to the narrow therapeutic range, with the risk of ischemic events increasing when the INR is below 2, and the risk of hemorrhagic events increasing above 3.5. 21 Costs associated with strokes are significant and sustained. It was estimated that the 2008 cost of ischemic strokes in Brazil was $329 million USD, the per-patient cost of hospitalization was $1902 USD, and the mean length of stay was over 13 days. 20 Hemorrhagic events also represent a substantial cost as part of the overall management of stroke risk for atrial fibrillation patients receiving oral anticoagulation treatment. 22 A US study has shown that non-adherence and underuse of warfarin by insured patients with AF has a negative impact on health and costs. It has also been demonstrated that the degree of anticoagulation control is directly correlated to improved outcomes for patients with atrial fibrillation receiving warfarin treatment. 23-25 Few studies have assessed the extent of anticoagulation control with warfarin in Latin American countries. Past research reported close to acceptable levels of anticoagulation control in Brazil, with TTR levels close to 60% in controlled settings 26-28 and between 60 and 65% in the real world. 9-11 However, these studies were conducted mostly in one or two public hospitals or anticoagulation clinics, in populations with limited sample size and broad use of warfarin. The TTR is the accepted measure of anticoagulation control for warfarin patients and is correlated with clinical outcomes. While often reported by center or even country in clinical trials, there is substantial heterogeneity in individual patient TTR. 29,30 The results from this current study are consistent with this concept in that even though the overall patient population had a fair TTR, in fact most of the patients had a TTR which was below the threshold considered optimal. 23 The present study furthers the understanding of the anticoagulation care model in routine clinical practice. It is representative of a relatively young AF population presenting with a lower prevalence of comorbidities than what has been reported in other observational studies and controlled settings. 26-28,31 In addition, the study is representative of real‑world data in a specific private setting of AMIL, including a structured programand phone calls, and it is not generalizable to other settings like the public sector. The approach to managing and regularly monitoring the patients through the care program was found to be quite unique. Studies that addressed a similar research question 9-11 did not report the existence of such a dedicated program for warfarin patients. INR monitoring was performed approximately once a month, more frequently than in other observational studies 32 but less than in controlled settings. 26 Despite the regular follow-up, only about half (49.1%) of all INR values drawn were in the therapeutic range and a limited portion of the population had good TTR control. The TTR results were consistent with past research within the care practice, indicating that warfarin patients spend only a 460