Oral Anticoagulation : the impact of the therapy in health-related quality of life at six-month follow-up 1

OBJECTIVE
to study the changes in health-related quality of life from beginning of anticoagulation therapy to six-month follow-up, and to study associations of sociodemographic and clinical characteristics with measures of quality of life and general health status at six-month follow-up, in individuals using oral anticoagulation due to various medical indications for the therapy.


METHOD
prospective study performed at a city in the state of Paraná, Brazil, composed of 78 patients. Measures included the Duke Anticoagulation Satisfaction Scale and the Medical Outcomes Survey Short Form SF-36.


RESULTS
mean age was 57 years (S.D.= 16) and 54% were women. Compared to the beginning of therapy, there was a statistically significant improvement in health-related quality of life at six-month follow-up. Linear regression analyses explained 32% and 30%, respectively, of the variance of the Duke Anticoagulation Satisfaction Scale and of the general health status. There was improvement in all components of the SF-36, except Mental Health.


CONCLUSION
The use of oral anticoagulation therapy was associated with improvement in health-related quality of life in the first six months of therapy. This study is longitudinal and therefore, has fewer limitations than cross-sectional studies published to date in the Nursing literature in Brazil.


Introduction
Oral anticoagulation therapy (OAT) is widely used to prevent and manage thromboembolic events; however, often its usage is difficult due to the fluctuations of blood coagulation values which require a rigorous laboratorial follow-up, and consequently, causing an impact in the quality of life of the OAT users (1) .Studies have investigated various aspects of health-related quality of life (HRQoL) in OAT users, such as limitations due to medication use, hassle and burden, and psychological impact, both negative and positive (2) .A study was conducted in an academic hospital of the state of São Paulo to assess the association between HRQoL and various factors, which included duration of medicament use and presence of complications resulting from the therapy.In this longitudinal study, 178 participants were interviewed and HRQoL was assessed through the eight domains of the Medical Outcomes Survey Short Form (SF-36).The results indicated that women, older Carvalho ARS, Ciol MA, Tiu F, Rossi LA, Dantas RAS.
adults, with diagnosis of atrial fibrillation, and with less than one year of OAT presented a lower HRQoL (3) .
In this study, we used the theoretical definition of HRQoL that focus on how much the disease or chronic condition, in addition to its symptoms, interfere in the person's daily life, that is, how much the affected person perceives the manifestations of the disease and its treatment (4) .In the clinical setting, the evaluation of the psychological impact, burden and limitations, and satisfaction with OAT might help to support interventions with the objective of increasing the adherence to OAT, and therefore, increasing the likelihood that the person is within the therapeutic levels and reducing the incidence of adverse events such as thromboembolism or hemorrhages (1) .
The participation of nursing professionals in clinics specialized in OAT is a practice still new in Brazil, although it has been often cited as practice in international studies.
In the Nursing area in Brazil, recent research involving OAT patients have used cross-sectional designs (3,(5)(6) , limiting the conclusions regarding the studied factors.
To address some of those limitations, the current study was designed to follow a sample of patients during the first six months of OAT.

Study design, location of study, and sample selection
This study was a prospective and observational study conducted in public and private health service institutions of a city of the Western region of Paraná state, Brazil.The study was approved by the hospital's human subjects ethic committee and the study objectives were explained verbally and in written to all participants.Individuals who agreed to participate signed an informed consent prior to data collection.
Inclusion criteria included individuals 18 years and older using OAT, who had initiated treatment no longer than two months prior to enrollment.This period is the average time needed to adjust the therapeutic dose of the medication, and it was used in a prospective cohort study of treatment adherence in the United States of America patients (7) .

Measures of HRQoL
The Medical Outcomes Survey 36-Item Short-Form (SF-36) (8) was used in its Portuguese validated version (9) to evaluate HRQoL in the four-week period prior to the interview.The SF-36 is composed of eight domains, each evaluated in a scale of 0 to 100, with larger values indicating better HRQoL in the respective domain.
The evaluation of the current general health status (GHS) was obtained through the question "In general, how do you rate your health today?", which was answered using a visual analogue scale (VAS) of 10 cm, anchored with the value 0 (worst health possible) on the left and 100 (best health possible) on the right.
Higher values indicated better evaluation of the GHS, according to the participant's perception at the time of the interview (10) .
The evaluation of HRQoL specific for oral coagulant users was performed using the Duke Anticoagulation Satisfaction Scale (DASS) (2) in its version validated for Brazil (11) , and applied to the participants at six months with OAT use, fewer limitations, less burden, and less psychological impact of the medication.

Statistical Analysis
Descriptive analysis was performed for all variables.
For objective 1, we compared the domains of SF-36, DASS, and GHS at baseline and six-month follow-up using the paired t-test.For objective 2, we performed linear regression analyses, using DASS and GHS at sixmonth follow-up as the response variables.

Discussion
Among the participants, there was a large proportion of women, with age of 60 years or older, and with atrial fibrillation.The proportion of older adults using OAT has increased around 7% per year in Brazil (12) , maybe because this age group presents comorbiditites that require use of OAT.Furthermore, the incidence of atrial fibrillation increases with age (13) , and studies have shown a large proportion of individuals 60 years or older who use OAT (7,(13)(14)(15) for that reason.
Our evaluation of HRQoL showed that there was an improvement in perceived health status and in the impact of OAT in the first six months of the therapy according to the three instruments we used: SF-36 (statistically significant improvement in all domains, except for Mental Health); GHS (statistically significant improvement); and DASS (small perceived impact of OAT).We did not find longitudinal studies of HRQoL in the literature that would allow us to compare our results in this population.
Currently, we can only compare our results to crosssectional studies conducted in other countries (2,(16)(17)(18) and in Brazil (3) .For the SF-36, Social Aspects was the domain that had the highest scores at baseline and six-month follow-up.Similar results were observed in a study in Brazil (3) and in international studies (7,14) .Other studies presented higher scores in other domains, such as Mental Health (18) and Emotional Aspects (16) ; however, in general, the participants of those studies were in different phases of the treatment with OAT.In our study, the domain with the worst score was Physical Aspects at baseline and Vitality at six-month follow-up.In contrast, other studies showed the following domains as the most compromised by OAT: Vitality (18) , Pain (16) , General Health (17)   , and Physical Aspects (2)(3) .In our study, at six-month follow-up, participants presented higher scores for all SF-36 domains than two of the reviewed studies (2)(3) , which evaluated individuals with longer duration of therapy (four and seven years, respectively).The only domain in our study that did not show a statistically significant change between baseline and six-month follow-up was Mental Health (scores of 72 and 74, respectively).In other studies, those values varied from 61 to 76 (2,3,16,18) .
Results from perceived general health status (GHS) showed improvement from baseline to six-month followup (mean change of 9 points, p<0.001), indicating that the participants, on average, perceived their health as better after starting OAT.
Regarding quality of life related to OAT, the results from the instrument DASS showed that the perceived impact of OAT was small.Since DASS is a relatively new instrument, publications using it are mostly of methodological nature, focusing on the psychometric properties of the instrument (2,11) .On those studies, the mean DASS was 54 and 58, which are higher values than the values in our study, indicating that our participants perceived a better quality of life related to OAT (lower scores represent higher satisfaction with OAT, less limitation, less hassle and burden, and less psychological impact).
In our study, individuals with deep vein thrombosis or pulmonary thromboembolism reported lower scores in HRQoL measures than individuals with mechanical valve prosthesis.We could not find information in the literature that could explain that difference.One possible explanation is the presence of pain among individuals with deep vein thrombosis or pulmonary thromboembolism.However, persons with mechanical valve prosthesis could also experience pain due to the surgical incision.It is possible that this latter group had time to prepare for the procedure (which is elective), and consequently, prepared for the OAT use.In contrast, the group with deep vein thrombosis or pulmonary thromboembolism had an acute event, which could have surprised them with its risk of imminent death, followed by the necessity of OAT and its demands for health care.
In the multiple linear regressions, the models explained 32% of the variance of DASS and 30% of the variance of GHS.Despite their clinical importance, the explanatory variables explained little of the variance of the response variables.We expected that the models would explain more of the variance, given that the 83% of the participants presented chronic conditions other than the reason for OAT and which also demand care, possibly making the participants to accept the implications that come with the treatment by OAT, and bringing less negative impact to their lives.The same reasoning can be used for number of medications used.For a person who already has the habit of taking daily medication for other chronic conditions, to add one more medication in the daily list might cause a lesser impact in their routine than the impact in the routine of a person who has to create the habit of taking the medication at the prescribed dose and times.A possible negative impact of prescribing OAT to a person who already takes other medications is the cost for the person and the family, which could interfere in the adherence to the treatment.However, among the participants of our study, it seems that cost was not the most important factor and it did not seem Carvalho ARS, Ciol MA, Tiu F, Rossi LA, Dantas RAS.
to interfere negatively in their HRQoL.One explanation is that most participants had enough income and/or were helped by their families to acquire the medication.
This fact was collected empirically by one of the authors during the interviews.Another study focusing on the perception of the OAT impact in the person's life, showed that many people abandon their old daily routines to adapt to the demands of OAT, which can bring some negative impact to their HRQoL, especially during the first few months of the treatment (1) .
However, despite the changes in routine required by OAT, there are individuals who report a positive impact in their lives, either because they feel protected from thromboembolic events prevented by OAT, or because the addition of OAT did not change their routines as they already used medication that required care and dedication to be adherent to it.We think that the latter occurred in our study, given the large number with other chronic conditions.
It is possible that there were influences from other factors in our study that could lead to some distortion in self-reporting, such as social desirability, which is the tendency that an individual has to answer question in a socially approved manner, in order to preserve his/ her self-image, to present him/herself in a favorable light, or to avoid negative consequences, such as reprehension (19) .
We believe that our results can help to direct planning for health care of persons using OAT, in issues related to reasons for prescription of OAT, changes in daily routine generated by OAT, and re-organization of health care to attend those demands.This study was important because it characterized the population being followed in our healthcare system as well as because it pointed to directions that need to be further investigated given the heterogeneity of the population and their response to the OAT.
One of the limitations of this study was the sample size, which was of moderate size but might not have been sufficient to study such a heterogeneous population.The data collection was done in two times only, which might not have been sufficient to describe the individual's trajectory during the period of adaption to OAT.In addition, the time between OAT initiation and the first interview, varied somewhat (within two months).Finally, the scarcity of options of valid and reliable instruments to measure HRQoL related to OAT, allowed us too few choices and at this point, there is not enough evidence that the measures we used are the best ones for the Brazilian population.

Conclusions
OAT can generate a negative impact in the lives of its users, given the routine necessary to maintain the treatment.This study contributed to the literature with the clinical evolution of OAT users, showing that it caused a positive impact in the individuals' lives at the end of six months of OAT.Future studies with larger sample sizes and longer follow-up periods are needed to increase our understanding of the oral anticoagulation therapy in the HRQoL of its users.
were: 1) to study the changes in HRQoL (evaluated by the eight components of the SF-36, the Duke Anticoagulation Satisfaction Scale [DASS], and perceived general health status) from the beginning of the treatment with oral anticoagulants to the end of six months of therapy, in a group of individuals initiating the treatment; 2) to study associations of sociodemographic and clinical characteristics (at baseline) with measures of DASS and general health status at six-month follow-up.
after beginning OAT.The DASS measures the satisfaction with treatment and the OAT-related quality of life.The scale is composed of 25 items, each with a five-point ordinal scale, and the sum of the items defines the total DASS.Lower DASS scores indicate greater satisfaction Rev. Latino-Am.Enfermagem 2013 Jan.-Feb.;21(Spec):105-12.

Table 1 .
There was improvement in all domains of the Both models had the following explanatory variables: age (in years), sex, reason for prescription of OAT (mechanical valve prosthesis, atrial fibrillation, or deep vein thrombosis/ thromboembolism/other), number of comorbidities, and presence of complications related to the therapy during the first six month of treatment.Significance level was set to 0.05.Due to exploratory nature of this research, the significance level was not adjusted for multiple comparisons.The results of this study should be interpreted as basis for future confirmatory studies.Data analysis was conducted using IBM SPSS (version 19.0 for Mac and 20.0 for Windows).SF-36 (p<0.002 for all domains), except for Mental Health (p=0.42).The largest improvement occurred for Physical Aspects, followed by Emotional Aspects, Functional Capacity, and Pain.Smaller improvements were observed for Social Aspects, General Health and Vitality.There was a statistically significant improvement in GHS measured by the visual analogue scale at sixmonth follow-up when compared to baseline (change of 9 points, p<0.001).The mean DASS at six-month follow-up was 45 (S.D. = 14, 95% confidence interval = [42, 48]), which represents a low impact of the OAT use perceived by the participants.Note that DASS is a measure of satisfaction and quality of life related to the use of OAT in individuals for whom the treatment is well-established, and therefore it was not applicable to the baseline interview.

Table 1 -
Measures of health-related quality of life (HRQoL) of participants at baseline (within 2 months from beginning of treatment) and at six-month follow-up of treatment with OAT.Cascavel,PR, Brazil, 2008-2009For the second objective, we performed two linear regression analyses using DASS and GHS at six-month follow-up as the response variables, and age, sex, reason for prescription of OAT, number of comorbidities, and presence of complications related to the therapy during the first six months as explanatory variables.GHS at baseline was also added to the linear regression for GHS at six months follow-up.Table2shows the results of the *OAT: Oral anticoagulation therapy; † p-value from paired t-test; ‡ NA = Not applicable www.eerp.usp.br/rlaeCarvalho ARS, Ciol MA, Tiu F, Rossi LA, Dantas RAS.

Table 3 -
Linear regression for general health status (GHS) measured by a visual analogue scale (VAS) at six months after beginning of oral anticoagulation therapy (OAT).Cascavel,PR, Brazil, 2008-2009