Measures of vitamin K antagonist control reported in atrial fibrillation and venous thromboembolism studies: a systematic review

Abstract

ObjectiveTo aid trialists, systematic reviewers and others, we evaluated the degree of standardisation of control measure reporting that has occurred in atrial fibrillation (AF) and venous thromboembolism (VTE) studies since 2000; and attempted to determine whether the prior recommendation of reporting ≥2 measures per study has been employed.DesignSystematic review.Search strategyWe searched bibliographic databases (2000 to June 2013) to identify AF and VTE studies evaluating dose-adjusted vitamin K antagonists (VKAs) and reporting ≥1 control measure. The types of measures reported, proportion of studies reporting ≥2 measures and mean (±SD) number of measures per study were determined for all studies and compared between subgroups.Data extractionThrough the use of a standardised data extraction tool, we independently extracted all data, with disagreements resolved by a separate investigator.Results148 studies were included, 57% of which reported ≥2 control measures (mean/study=2.13±1.36). The proportion of time spent in the target international normalised ratio range (TTR) was most commonly reported (79%), and was frequently accompanied by time above/below range (52%). AF studies more frequently reported ≥2 control measures compared with VTE studies (63% vs 37%; p=0.004), and reported a greater number of measures per study (mean=2.36 vs 1.53; p<0.001). Observational studies were more likely to provide ≥2 measures compared with randomised trials (76% vs 33%; p<0.001) and report a greater number of measures (mean=2.58 vs 1.63; p<0.001). More recent studies (2004–2013) reported ≥2 measures more often than older (2000–2003) studies (59% vs 35%; p=0.05) and reported more measures per study (mean=2.23 vs 1.48; p=0.02).ConclusionsWhile TTR was often utilised, studies reported ≥2 measures of VKA control only about half of the time and lacked consistency in the types of measures reported. A trend towards studies reporting greater numbers of VKA control measures over time was observed over our review time horizon, particularly, with AF and observational studies.

Vitamin K antagonist use: evidence of the difficulty of achieving and maintaining target INR range and subsequent consequences

“…Despite 60 years of clinical experience, the maintenance of stable INR in patients using VKA remains a challenging task. While numerous metrics have been used in clinical studies of VKAs to assess the quality of anticoagulation control [ 9 , 10 ], time in therapeutic range (TTR) (most commonly calculated using Rosendaal’s method of linear interpolation [ 11 ]) is the most frequently reported. Experts have suggested that the minimum target TTR should be no less than 65 % [ 12 – 15 ] but this goal is often not met [ 16 – 22 ] even in modern day RCTs [ 23 – 32 ] (Table 1 ).…”

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico

“…27 In a meta-analysis, only 56 % of patients had INRs within the desired range, with a TTR of barely 61 %; recurrent thrombosis occurred in > 50 % of the patients when INR was < 2, and > 40 % of hemorrhages appeared with an INR above the desired range. 3 Another study analyzed routine clinical practice with TTR; 28 with the desired INR range between 2.0 and 3.0, 58.9 % of the patients had a TTR < 65%. 28 Patients with poor INR control were shown to have a higher risk of stroke, major bleeding, and all-cause mortality.…”

“…VKAs still constitute a type of treatment commonly used in clinical practice, since they are backed by a large amount of evidence generated in clinical trials, which support their efficacy; their use is endorsed by countless national and international guidelines. [1][2][3] Maintaining VKA therapy control quality is necessary for reducing thrombotic and hemorrhagic complications associated with VKA use, which is why frequent monitoring of their effect is required. However, these anticoagulants are not easy to manage due to their multiple interactions with food and drugs, and because they are often indicated in elderly patients with multiple comorbidities.…”

Análisis de la calidad de la anticoagulación con antagonistas de la vitamina K en tres escenarios clínicos en México

“…27 En un metaanálisis, solo 56 % de pacientes tenían INR dentro del rango deseado con TRT de apenas 61 %; en > 50 % de los pacientes ocurrieron trombosis recurrentes cuando el INR era < 2 y > 40 % de las hemorragias apareció con INR superior al rango deseado. 3 Otro estudio analizó la práctica clínica rutinaria con el TRT; 28 con el rango de INR deseado entre 2.0 y 3.0, 58.9 % de los pacientes presentó TRT < 65 %. 28 Se mostró que el paciente con control pobre del INR tiene más riesgo de enfermedad vascular cerebral, hemorragia mayor y mortalidad por todas las causas.…”

“…Aún constituyen un tipo de tratamiento frecuentemente empleado en la clínica, ya que tienen a su favor una gran cantidad de evidencia generada en ensayos clínicos, los cuales sostienen su eficacia; su uso es avalado por innumerables guías nacionales e internacionales. [1][2][3] Mantener la calidad del control de la terapia con los AVK es necesario para reducir las complicaciones trombóticas y hemorrágicas asociadas a su uso, por lo cual se requiere un control frecuente de su efecto. Sin embargo, estos anticoagulantes no son fáciles de manejar debido a sus múltiples interacciones con alimentos y medicamentos y porque en numerosas ocasiones se indican en pacientes de edad avanzada con múltiples comorbilidades.…”