IJCS | Volume 32, Nº2, March/April 2019

111 Colet et al. Adverse events in warfarin users Int J Cardiovasc Sci. 2019;32(2)110-117 Original Article The high frequency of interactions of warfarin with other drugs has been described in studies with hospitalized patients. 7,8 Nevertheless, studies evaluating drug-drug interactions in primary health care are less common. If, on the one hand, these patients generally use less medication than hospitalized patients due to their less severe conditions, monitoring of diet and medication use is less frequent. The aim of this study was to evaluate the occurrence of adverse effects related to drug-drug interactions in warfarin users in the primary health care. Methods Study design and subjects This was an open cohort, prospective study with descriptive analysis with all warfarin users attending public health clinics of the city of Ijuí, located in the south of Brazil. Patients were followed for an 18-month period between April 2014 andOctober 2015, bymonthly interviews conducted in patients’ home. This was an open cohort because patients were prospectively recruited in the first six months of follow-up. Warfarin users were identified using copies of drug prescriptions, filed at Ijui Secretary of Health Central Pharmacy. It is the place where all prescriptions issued in the city are filed. Patients’ address and telephone number registered in the medical records were used for scheduling of visits. Inclusion criteria were patients living in Ijui, Brazil, on oral warfarin therapy for chronic diseases or who initiated therapy in the first six months of the study, and who had their medication dispensed from Ijui public health centers. All participants signed an informed consent form. Patients living in other cities, patients treated with other anticoagulants, and those who acquired medications in private pharmacies were excluded. Data were collected with the aid of a questionnaire containing questions about the patient – socioeconomic and demographic characteristics; medications – use of warfarin and other drugs prescribed; and foods – types and amounts of certain foods consumed. Data analysis Medications were classified at the first level of the Anatomical Therapeutic Chemical (ATC) coding system, 9 used for the classification of drugs according to their sites of action and therapeutic and chemical properties. Results related to the medications used by the patients are presented as mean and standard deviation. Drug interactions were classified according to Micromedex 10 database, and only severe and moderate interactions were considered for analysis. Assessment of drug interactions was performed at two time points – first, at the 18th month of patients’ follow-up and then at the occurrence of a clinical event (bleeding or venous thromboembolism). These events were identified by self- report and confirmed by data documented in the medical records. Bleeding and venous thromboembolism were categorized by the site of occurrence only, not considering the severity. For analysis of drugs and their interactions, we included only continuously used medications, based on their prescriptions. Because of the high use of simvastatin and its potential interactionwithwarfarin, patients’ cardiovascular riskwas assessed by the Framingham score, which evaluates and scores each of the following risk factors – age, systolic and diastolic blood pressure, smoking, diabetesmellitus (DM), total cholesterol (TC) andHDL-TC. Resultswere expressed as absolute risk of fatal (death) and non-fatal (acute myocardial infarction and angina pectoris) cardiovascular events in ten years. Individuals with a risk equal to or lower than 9% were classified as “low-risk” (LR); those with a risk between 10%and 19%as “moderate risk” (MR) and patients with a risk equal to or higher than 20%were classified as high risk (HR). 11 Age, smoking and DMwere self-reported, andDMwas confirmed by the use of glucose lowering drugs. Blood pressure was measured at the first interview, and TC and HDL-CT at month 18. Frequency and amount of vitamin K consumed was evaluated using an instrument developed for the Portuguese population and validated by Ferreira. 11 Based on their responses, patients were classified by vitamin K consumption into one of the four categories – high, moderate, low and very low consumption. Values of international normalized ratio (INR) were used for calculation of the Time in Therapeutic Range (TTR), according to the method adapted and validated by Schimidt et al. 12 Results were expressed as interquartile range. Statistical analysis was performed using the SPPSS software version. All patients signed the informed consent form. The study was approved by the ethics committee of the Federal University of Rio Grande do Sul (approval number 336.259/2013).