Adverse events in patients initiated on dabigatran etexilate therapy in a pharmacist-managed anticoagulation clinic

Abstract

BackgroundVitamin K antagonists have been the treatment of choice in preventing thromboembolic events, but problems such as frequent dose adjustment and monitoring of coagulation status, including multiple drug and food interactions, make their use difficult. Dabigatran etexilate is a new oral direct thrombin inhibitor not requiring routine monitoring and since its approval in the United States, many clinicians have been interested in utilizing this new therapy.ObjectiveThis study documented adverse drug events (ADEs) recorded in patients started on dabigatran therapy, including those who were previously controlled on warfarin and those who were anticoagulant naïve.MethodsIn an outpatient pharmacist-managed anticoagulation clinic, a total of 221 patients were initiated on dabigatran therapy over an 18-month period. 43.0% of these patients were previously controlled on warfarin.Results54 of the 221 patients (24.4%) developed an ADE while on dabigatran. The average time to event was 48.4 days. Nine of the fifty-four patients experienced a major bleeding ADE; six patients developed a serious non-bleeding ADE. Five of these fifteen patients died; one death was directly related to dabigatran therapy. The remaining thirty-nine of the fifty-four patients experienced a clinically relevant non-major ADE. Of the fifty-four patients who experienced an ADE, thirty were male. The average age was 73.8 years and the average weight was 92.8kg. Fifty-four percent of those who experienced an ADE were previously anticoagulant naïve.ConclusionsWhile many clinicians have been interested in utilizing the new direct thrombin inhibitor dabigatran etexilate, this new therapy is not without risks. This study documented adverse drug events in 24.4% of patients who were initiated on dabigatran etexilate therapy over an eighteen month period. ADEs were more common in patients who were anticoagulant naïve prior to dabigatran etexilate therapy and not those who were previously controlled on warfarin therapy.

Prevalence, contributory factors and severity of medication errors associated with direct-acting oral anticoagulants in adult patients: a systematic review and meta-analysis

“…Out of the 32 studies, 12 (40.7%) were conducted in the USA [ 15 , 19 , 20 , 24 , 33 , 35 , 37 – 40 , 42 , 44 ]; three each in the UK (11.1%) [ 22 , 34 , 45 ] and France [ 18 , 30 , 46 ]; two each in Belgium [ 31 , 36 ], Greece [ 27 , 28 ], Australia [ 23 , 41 ], Ireland [ 29 , 32 ]; and one each in the Netherlands [ 21 ], Spain [ 43 ], Turkey [ 17 ], Israel [ 16 ], Denmark [ 25 ], and United Arab of Emirates [ 26 ]. Studies were conducted in university-affiliated or academic/teaching hospitals [ 15 , 16 , 18 , 23 , 25 , 28 – 31 , 34 , 36 , 37 , 39 , 41 , 43 , 45 , 46 ], tertiary care non-teaching hospitals [ 24 , 26 , 33 , 35 , 38 , 42 ], primary healthcare centres [ 22 , 43 ], nursing home [ 19 ], private general hospital [ 27 ], pharmacist managed anticoagulation clinic [ 20 ], central medication registration [ 21 ], Poison control system [ 40 ], single center [ 32 ], and patient safety reporting system [ 44 ].…”

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.…”

“…Moreover, numerous studies from different countries worldwide arrived at the same conclusion that anticoagulants represent a high-risk medication and are a threat to patient safety (Saedder et al, 2014). However, only limited studies examining the MRPs of new oral anticoagulants have been carried out in real world clinical practice (Donaldson and Norbeck, 2013).…”

Pharmacist-managed clinics for patient education and counseling in Japan: current status and future perspectives

“…In addition to warfarin, novel oral anticoagulants such as Factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, as well as a direct thrombin inhibitor, dabigatran etexilate, have recently become available for anticoagulation therapy [ 52 ]. Because these new drugs also have some risks for bleeding and other ADEs [ 61 , 62 ], we have included pharmaceutical education and counseling on novel oral anticoagulants in the PMC at Nagoya University Hospital.…”