Atrial fibrillation (AF) is the most prevalent arrhythmia in the world. It is considered a current epidemic and one of the main causes of ischemic stroke, usually with severe and debilitating conditions, and is responsible for systemic cardioembolic phenomena, increased number of cases of congestive heart failure (CHF), cognitive impairment related to silent embolic phenomena, and increased overall mortality in affected patients.

Vitamin K antagonists (VKA) represented in the vast majority of studies with warfarin have been widely used for many years; however, they have complex adherence due to several factors, including the need for frequent INR monitoring, regular dose adjustments for maintaining a suitable time in therapeutic range (TTR) (>= 70%) and interactions with a number of drugs and foods, which contributed to its ever decreasing use. Direct-acting anticoagulants (DACs), represented by dabigatran, rivaroxaban, apixaban and, more recently, edoxaban, offer an alternative to VKA, without the disadvantages presented by the latter.

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Abstract

Background:

Warfarin is an oral anticoagulant involved in important interactions with foods and other drugs.

Objectives:

To evaluate the occurrence of adverse events reported by warfarin users and their relationship with drug interactions.

Methods:

This was an open cohort, prospective study conducted in an 18-month period with warfarin users attending public health clinics of the city of Ijuí, Brazil. Data were collected by means of interviews administered at patients’ home every month. Patients’ responses were confirmed by review of medical records when patients sought medical care. Data were analyzed by descriptive statistics. Potential drug interactions were evaluated in a database and vitamin K consumption was quantified using a validated method.

Results:

A total of 68 patients were followed-up; 63 completed the study and 5 died in the study period. Mean number of medications taken by the patients was 9.6 ± 4.5, and mean number of interactions involving warfarin was 2.91 ± 1.52. Most potential interactions increased the risk of bleeding, 61 of them severe interactions and 116 moderate interactions. Eighty-seven episodes of bleeding and 4 episodes of thrombosis were reported by a total of 37 and 4 patients, respectively. At the occurrence of these events, 56.5% of warfarin users were also taking omeprazole, 35.9% were taking simvastatin and 25.0% paracetamol. Most patients had a low vitamin K intake.

Conclusions:

A high frequency of potential interactions between warfarin and other drugs was detected, but a low intake of foods that could possibly affect the effects of warfarin was observed. Based on our results, it seems prudent to follow patients on warfarin therapy for drug-drug interactions, aiming to control adverse effects and to promote a safe and effective therapy.