Continuation of Dabigatran Therapy in “Real-World” Practice in Hong Kong

Abstract

BackgroundDabigatran, an oral direct thrombin inhibitor, possesses several advantages over warfarin that can in principle simplify the management of stroke prevention in atrial fibrillation (AF). Nonetheless it remains unclear whether these advantages can translate to clinical practice and encourage long-term therapy. The objective was to describe long-term dabigatran therapy for stroke prevention in AF and to identify risk factors for discontinuation of therapy.Methods and ResultsWe studied 467 consecutive Chinese patients (72±11 years, male: 53.8%) with a mean CHA2DS2-VASc score of 3.6 prescribed dabigatran for stroke prevention in AF from March 2010 to September 2013. Over a mean follow-up of 16 months, 101 patients (21.6%) permanently discontinued dabigatran. The mean time-to-discontinuation was 8 months. The most common reason for discontinuation was dyspepsia (30.7%), followed by other adverse events (17.8%) such as minor bleeding (8.9%), major gastrointestinal bleeding (7.9%), and intracranial hemorrhage (1%). Other reasons included dosing frequency (5.9%), fear of side effects (4.0%), lack of laboratory monitoring (1.0%), and cost (1.0%). Multivariable analysis revealed that low baseline estimated glomerular filtration rate (p = 0.02), absence of hypertension (p = 0.01), and prior use of a proton-pump inhibitor (p = 0.02) and H2-receptor blocker (p = 0.01) were independent predictors of drug discontinuation. In addition, there were altogether 9 ischemic strokes (1.5%/years), 3 intracranial hemorrhages (0.5%/year), and 24 major gastrointestinal bleedings (4.1%/year).ConclusionDabigatran discontinuation is very common amongst Chinese AF patients. This reveals a management gap in the prevention of stroke in AF.

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

“…The study duration ranged from 10 ( Thorne et al, 2014) to 23 (Gorst-Rasmussen et al, 2015) months and the sample sizes ranged from 150 (Hu et al, 2015) to 27,514 (Martinez et al, 2016) subjects. The data collection method involved electronic medical record reviews (Donaldson and Norbeck, 2013;Lee et al, 2013;Cutler et al, 2014;Ho et al, 2014;Monteagudo et al, 2015;Martinez et al, 2016), electronic national database searches Larsen et al, 2013;Graham et al, 2014;Beyer-Westendorf et al, 2015;Chang et al, 2015;Gorst-Rasmussen et al, 2015;Hu et al, 2015;Chan et al, 2016;Forslund et al, 2016;Nishtala et al 2016), questionnaires (Thorne et al, 2014;Hu et al, 2015), and a reporting system (Andreica and Grissinger, 2015). The settings of these studies were in hospitals, primary care centres, or both.…”

“…Four of the retrospective studies investigated ADRs (Larsen et al, 2013;Graham et al, 2014;Chang et al, 2015;Nishtala et al, 2016], one investigate medication errors (Andreica and Grissinger, 2015), one investigated persistence (Forslund et al, 2016), and two investigated adherence (Lee et al, 2013;Cutler et al, 2014). Furthermore, six prospective studies investigate ADRs (Donaldson and Norbeck, 2013;Ho et al, 2014;Thorne et al, 2014;Beyer-Westendorf et al, 2015;Monteagudo et al, 2015;Chan et al, 2016), one study investigate persistence (Martinez et al, 2016), and two investigate adherence (Gorst-Rasmussen et al, 2015;Hu et al, 2015). In addition, most of the studies investigated dabigatran, which was the first DOAC available in the market.…”

“…al., 2012). In the prospective studies, the reported ADRrelated bleeding events ranged between 2.3% (BeyerWestendorf et al, 2015) and 16.8% (Ho et al, 2014) of the surveyed population. The rate of non-compliance to dabigatran was 11.3% (Hu et al, 2015) and rates of adherence after one year was 76.8% (Gorst-Rasmussen et al, 2015).…”

Fibrilación auricular: enfoque para el médico no cardiólogo

“…Estudios postmercadeo recientes confirman la seguridad y eficacia de dabigatran y rivaroxaban en pacientes con FA no valvular (36,38), aun sin contar con estudios postmercadeo para apixaban y edoxaban que reporten datos de seguridad y eficacia en mundo real. Existen múltiples registros que describen el uso de los anticoagulantes directos fuera de los ensayos clínicos controlados, donde se ha evidenciado una tendencia de uso de los anticoagulantes directos cada vez mayor, prefiriendo estos frente a warfarina en pacientes de edad avanzada, con riesgo alto de sangrado, riesgo alto de eventos embólicos y mayor tasa de comorbilidades (26,(42)(43)(44)79); excepto para dabigatran, que tiende a prescribirse más en pacientes jóvenes, con riesgo de sangrado menor y menos tasa de comorbilidades que se cree está relacionada con la mayor tasa de sangrado observada en los datos del estudio RE-LY y en los diferentes metanálisis y estudios de registro (26,(42)(43)(44)79). Una de las preocupaciones existentes respecto a la seguridad de estos nuevos agentes era la ausencia de terapias para la reversión de su efecto ante un evento de sobreanticoagulación o sangrado mayor (12, 16-18, 26, 27, 39, 40, 42, 43, 80), que se ha superado parcialmente tras contarse actualmente con antídoto contra los inhibidores directos de trombina (idarucizumab) (1, 5, 80-82) e inhibidores del factor Xa (adexanet alfa) (1,5,80,83) que han sido seguros y eficaces en estudios fase II (81, 83) con aprobación para idarucizumab por la FDA y EMA tras la publicación preliminar de seguridad y eficacia del estudio fase III (82), teniendo en cuenta que ninguno de ellos esta aun disponible en el medio.…”

“…La guía de práctica clínica Europea recomienda usar la dosis menor efectiva de los anticoagulantes (5) por el mayor riesgo de sangrado que tienen estos pacientes. Esta recomendación no ha sido evaluada de forma prospectiva en estudios clínicos por lo cual los autores de la presente revisión recomiendan mantener la dosis indicada según la función renal, peso y edad del paciente, ya que estudios observacionales (26,36,38,43) han demostrado que el uso de dosis menores de las recomendadas de los anticoagulantes directos por razones diferentes a las recomendadas por los estudios clínicos se asocian a mayor tasa de mortalidad y eventos tromboticos.…”