MEDICINSKI GLASNIK - Aktuelno Ljekarska komora ZE - DO kantona

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Medicinski Glasnik, Volumen 8, Number 1, February 2011
INTRODUCTION
Despite the continuously growing number of atrial
fibrillation patients (1) and increased possibility
of development of new ones, more specific and
potentially more stable anticoagulants, the usage
of old oral anticoagulants, warfarin and acenocoumarol
is still increasing (2,3). These drugs are
in the top 100 of the most prescribed drugs in the
world (4). The increased usage of these drugs was
noted from the early nineties until today, especially
in the North America and Western Europe
(5). Comparative studies of vitamin K antagonists,
warfarin and acenocoumarol are rare, probably
due to their geographical distribution according
to which certain regions use only warfarin
while other regions use only acenocoumarol (6).
Warfarin is the first line drug for North America,
Scandinavia and Great Britain. Although unavailable
in the United States of America, most European
countries, including Germany, have acenocoumarol
as the first line drug (7,8). In other parts
of Europe and elsewhere, acenocoumarol is often
used as an alternative drug to warfarin.
Due to its longer elimination half-life (30-80 hours,
mostly around 37 hours), most of the authors
(9-13) consider warfarin treatment to be better
and more stable as compared to acenocoumarol.
Yet, there are studies that deny this hypothesis
(14-17). The narrow therapeutic index of vitamin
K antagonists, next to multifactorial variations,
creates difficulties in maintaining optimal coagulation
status which prevents thrombose and
avoids bleeding (18-22). Maintenance of referent
International normalised ratio (INR) values (2.0-
3.0) is basic criteria of safety and effectiveness of
oral anticoagulant treatment (3,23,24).
The aim of this study was to compare the individual
quality and stability of long-acting warfarin
and short-acting acenocoumarol in patients with
nonvalvular atrial fibrillation (NVAF). After an
analysis of the relevant databases we found this
study to be the first comparative study of the oral
anticoagulant treatment in Bosnia and Herzegovina,
where patients have both drugs available
PATIENTS AND METHODS
Study design
This was an observational, comparative, bidirectional
(prospective/retrospective) one-year
clinical study, conducted in the Blood Transfusion
Institute Sarajevo, Bosnia & Herzegovina.
The study was conducted according to the GCP
(Good Clinical Practice), GLP (Good Laboratory
Practice) and local ethical principles.
Patients
All patients with atrial fibrillation (AF) who
were using warfarin/acenocoumarol and were
previously monitored by the Blood Transfusion
Institute were eligible. In the three-month period,
213 patients were screened and 137 patients
met inclusion criteria (age of 40-80, diagnosed
NVAF, CHADS 2 index score ≥2 (25), the planned
long-term treatment with warfarin/acenocoumarol
which started at least 2 months prior to the
observational period). The diagnosis of NVAF,
indication for oral anticoagulant treatment and
target INR range were determined in competent
specialised institutions and adequately documented
by medical records. The patients were divided
into two parallel groups of 60 patients. In
order to avoid a bias, the groups were composed
according to the anticoagulant therapy (warfarin/
acenocoumarol) as well as their gender and age.
The duration of the observational period was
12 months. The first six months from the day of
screening were observed retrospectively, and the
following six months prospectively. The control
visits and blood sampling for INR control were
performed on a monthly basis, or more frequently
if necessary.
Data collection
Anamnestic data collected during the screening
visit (age, gender, weight, height, CHADS 2 index,
comorbidities, concomitant drugs, smoking
and alcohol use) were collected in a study sheet.
Retrospective data (dates of INR measurements,
INR values and the daily warfarin/acenocoumarol
doses) for six months period prior to enrolment
were collected via retrospective chart
review of monthly patient organisers and gathered
in a specially designed Patient’s Diary. For
the following six months, the same data, as well
as additional data (adherence to the treatment,
temporary or permanent interruptions of the treatment
and adherence to the low vitamin K intake
diet) were assessed and collected at each visit
prospectively.