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versión impresa ISSN 0212-1611
Nutr. Hosp. vol.27 no.4 Madrid jul.-ago. 2012
Does treatment guided by vitamin K in the diet alter the quality of life of anticoagulated patients?
¿El tratamiento guíado por la Vitamina K en la dieta altera la calidad de vida de los pacientes anticoagulados?
M. C. Silva de Assis1, L. Nascimento Cruz1, P. Zuchinali1, L. E. Rohde1, E. Rejane Rabelo1,2
1Universidade Federal do Rio Grande do Sul Postgraduate Program of Cardiovascular Science: Cardiology. Cardiology Division. Hospital de Clinicas de Porto Alegre
2Universidade Federal do Rio Grande do Sul. School of Nursing Postgraduate Program. Brazil
This study was supported by the Hospital de Clínicas de Porto Alegre Research Incentive Fund.
Purpose: To compare whether health-related quality of life (HRQoL) is altered in patients undergoing a treatment strategy guided by changes in dietary vitamin K.
Methods: This study is a randomized clinical trial carried out with chronic oral anticoagulation outpatients randomized into a control group (conventional dose adjustment of oral anticoagulants) (n = 66) and an intervention group (strategy based on changes in dietary vitamin K intake) (n = 66). HRQoL was measured using the Duke Anticoagulation Satisfaction Scale (DASS) at baseline and 90 days of follow-up.
Results: Patients with worse HRQoL were younger (p = 0.005) and were using a higher dose of baseline oral anticoagulants (p = 0.008), while those with better HRQoL scores had a higher level of education (p = 0.01). Both groups had significant improvements in HRQoL from baseline to 90 days in the global DASS score (p < 0.001), as well as in the negative and positive psychological impact (p < 0.001) domains. We did not observe differences in the variations of HRQoL scores in any of the DASS domains (p values > 0.05) between groups of interventions. Patients who achieved oral anticoagulation stability (n = 23) had significantly better HRQoL scores than patients who did not achieve stability (p = 0.003).
Conclusion: Patients receiving the treatment strategy based on changes in dietary vitamin K intake did not have better HRQoL scores; however, both treatment approaches to manage oral anticoagulation improved HRQoL. Patients with greater oral anticoagulation stability had better HRQoL scores.
Key words: Vitamin K. Diet. Anticoagulants. Quality of Life. Clinical Trial.
Objetivo: Comparar si la calidad de vida relacionada a la salud (CVRS) se ve alterada en los pacientes sometidos a una estrategia de tratamiento guiado por cambios en la ingesta de vitamina K en la dieta.
Métodos: El estudio es un ensayo clínico aleatorizado llevado a cabo con pacientes ambulatorios crónicos de anticoagulación oral con asignación al azar o en un grupo control (ajuste de la dosis convencional de anticoagulantes orales) (n = 66) o en un grupo intervención (estrategia basada en los cambios en la ingesta de vitamina K) (n = 66). La CVRS se midió utilizando el instrumento Duke Anticoagulation Satisfaction Scale (DASS) al inicio y 90 días de seguimiento.
Resultados: Los pacientes con peor CVRS eran más jóvenes (p = 0,005) y estaban utilizando una dosis más alta de los anticoagulantes orales de referencia (p = 0,008), mientras aquellos con mejores puntajes de CVRS tenían un mayor nivel de educación (p = 0,01). Ambos grupos tuvieron mejoras significativas en la CVRS desde el inicio hasta 90 días en la puntuación global de DASS (p < 0,001), así como en el los dominios impacto psicológico positivo y negativo (p < 0,001). No se observaron diferencias en las variaciones de las puntaciones de CVRS en cualquiera de los dominios DASS (valores de p > 0,05) entre los grupos de intervención. Los pacientes que lograron la estabilidad de la anticoagulación oral (n = 23) tuvieron significativamente mejores puntaciones de CVRS que los pacientes que no lograron la estabilidad (p = 0,003).
Conclusión: Los pacientes tratados con la estrategia de tratamiento basada en los cambios en la ingesta de vitamina K no tuvieron mejores puntuaciones de CVRS, sin embargo, ambos enfoques al tratamiento para manejar la anticoagulación oral mejoró la CVRS. Los pacientes con una mejor estabilidad en la anticoagulación oral tuvieron mejores puntaciones de CVRS.
Palabras clave: Vitamina K. Dieta. Anticoagulantes. Calidad de Vida. Ensayo Clínico.
HRQoL: Health-related quality of life.
INR: International Normalized Ratio.
Despite the exponential increase in studies evaluating health-related quality of life (HRQoL) as an important outcome in patients with several chronic diseases, data in an anticoagulated patient population are still scarce in the relevant literature. The evidence currently available has shown that monitoring these patients in specialized clinics leads to more chronic oral anticoagulation stability, lower incidence of bleeding and ischemic events and improved HRQoL.1-3 On the other hand, patients treated in general clinics are at higher risk of bleeding and thrombosis, therefore impacting on HRQoL.4-6
Among the existing strategies to control oral anticoagulation, anticoagulant dose adjustment has been the first method of choice of most professionals. However, recently, changes in vitamin K intake in the diet have emerged as an attractive option to manage patients outside the therapeutic target based on the International Normalized Ratio (INR) of the prothrombin time. Our group has recently demonstrated through a randomized clinical trial that management guided by modulation of vitamin K in the diet improves the stability of oral anticoagulation when compared to patients treated conventionally. Moreover, this dietary based strategy seems to be safer, demonstrating a strong tendency for a lower occurrence of adverse events inherent in oral anticoagulation, such as bleeding or thrombosis.7
Despite evidence showing that the HRQoL of anti-coagulated patients followed up in specialized clinics is improved,1-7 the impact of different management strategies of anticoagulation on specific scales of HRQoL, and whether there is a significant association between HRQoL parameters and oral anticoagulation stability and/or adverse events, are unknown. The present study was performed to evaluate the variation of HRQoL scores measured by the Duke Anticoagulation Satisfaction Scale, a novel and specific instrument for anticoagulated patients, according to two different strategies to manage oral anticoagulation.
Patients and study design
Data on INR values and HRQoL used for the present analysis were derived from a randomized clinical trial in which 132 patients were evaluated from the anticoagulation clinic of a university tertiary care hospital in Porto Alegre, Brazil. Patients were randomized into a control group (a strategy treatment based on conventional dose adjustment of oral anticoagulants) and an intervention group (a strategy treatment based on pragmatic changes in dietary vitamin K intake according to INR values). The protocol was registered at Clinical-Trials.gov (http://clinicaltrials.gov) as NCT00355290. The study was approved by the Research Ethics Committee of our institution, and complies with the Declaration of Helsinki. Detailed data from the study protocol described in the original publication7. Briefly, prospective and sequential data on INR values and HRQoL were collected at baseline and 90 days after randomization. For atrial fibrillation, the INR target was 2.5 (from 2.0 to 3.0), and patients were considered to be eligible if the observed INR was 1.5 to 1.99 or 3.01 to 4.0. For valvular prosthesis, the INR target for most patients was 3.0 (from 2.5 to 3.5), and they were considered to be eligible if the observed INR was 1.5 to 2.49 or 3.51 to 4.0. For inclusion in the study, patients had to have been using oral anticoagulants for more than three months, and the last INR had to be outside the therapeutic target, with no definite cause for instability. Patients with the following criteria were excluded: extreme values of INR (< 1.5 or > 4.0) and evidence of bleeding or thrombosis. In this study, stability was defined as the number of times that the INR was in therapeutic range in the follow-up phase.
Instrument for quality of life
HRQoL was measured in both groups through the instrument Duke Anticoagulation Satisfaction Scale, a specific instrument for assessing HRQoL for anticoagulated patients,8 at baseline (randomization visit) and at the final study visit, which occurred 90 days after inclusion. This instrument was adapted to and validated for the Portuguese variant spoken in Brazil featuring adequate reliability (Cronbach's alpha of 0.79). It consists of 25 items covering three dimensions related to oral anticoagulation: limitation (Cronbach's alpha 0.72), task/burden (Cronbach's alpha 0.76), and positive (Cronbach's alpha 0.67) and negative (Cronbach's alpha 0.38) psychological impact9. With respect to descriptive analysis, studies of construction and validation present Duke Anticoagulation Satisfaction Scale scores in two ways: the sum of the responses to 25 items (possible range 25 to 175) or by averaging the responses to 25 items (possible range 1 to 7). For the current analysis, we opted to use the averaging system.
The limitation domain has nine items, the task domain has eight items, the positive psychological impact domain has five items, and the negative psychological impact has three items. Obtaining the numerical values of the total scale is possible by averaging the responses to items, as well as obtaining the numerical values of the sub-scales. Lower values of scales depict improved HRQoL.
Variables were assessed according to their characteristics and distribution, using parametric or nonparametric tests in the assessment of absolute or percentage differences between dependent samples. To compare clinical and demographic characteristics, patients were divided into quartiles according to the score on the Duke Anticoagulation Satisfaction Scale scale and grouped into two major groups: upper (HRQoL scores above 1.88) and lower (scores below 1.52). For comparison of HRQoL scores over time in the group guided by dietary vitamin K changes and in the control group (conventionally managed), a paired t-test was used for comparing different moments. To assess whether the difference (A) in HRQoL scores was attributable to the type of intervention, the presence or absence of bleeding, stability and adherence, an interaction variable between the groups was created, obtained from the difference between the baseline HRQoL score (Pre) and the final HRQoL score (Post). For this analysis, we used ANOVA for repeated measures to compare the two groups over time, as well as to evaluate the final scores of HRQoL in both groups when comparing bleeding (presence or absence), stability and adherence. P values < 0.05 (two-tailed) were considered statistically significant. Data were analyzed using the statistical PASW application Statistics 18.0 (IBM SPSS software).
132 patients (66 in each group) who met the inclusion criteria and consented to participate in the protocol were included. Detailed data of the enrolled patients were previously described.7 Demographic and clinical characteristics of patients were compared by stratifying the studied population into two groups according to extremes of HRQoL scores at baseline (upper and lower quartiles). We observed that patients with worse HRQoL were younger (p = 0.005) and were using a higher dose of baseline oral anticoagulant (p = 0.008). On the other hand, those with a higher level of education had improved HRQoL (p = 0.01) (table I).
Comparing baseline and the post-intervention period, the group guided by vitamin K in the diet had improvements in the total HRQoL score (p < 0.001) and in the limitation (p = 0.04), task (p = 0.02), negative (p < 0.001) and positive psychological impact (p < 0.001) domains. For the control group, there was an improvement in the total HRQoL score (p = 0.02), as well as in the negative (p < 0.001) and positive psychological impact (p < 0.001) domains (table II).
When assessing whether differences in HRQoL scores could be attributable in part to differences between interventions (dietary vitamin K guided versus conventional management), we found no significant difference between the variations of HRQoL in the groups: total HRQoL score (p = 0.41) and limitation (p = 0.44), task (p = 0.24), psychological impact (p = 0.61), positive (p = 0.76) and negative psychological impact (p = 0.65) domains (last column of table II).
We did not observe any significant interaction of HRQoL scores and the presence (n = 7) or absence (n = 119) of bleeding and adherence (n = 105) or not to treatment (n = 21) (fig. 1A e 1B). However, HRQoL scores were higher in patients who achieved oral anticoagulation stability (n = 23) [100% of INRs within the therapeutic range], when compared to patients with lower oral anticoagulation stability (p = 0.003) (fig. 1C).
In the present study, we have confirmed that HRQoL scores improve over a relatively short period of follow-up. This improvement had a similar magnitude in both groups regardless of allocation (dietary change versus anticoagulant dose adjustment). Notably, patients who achieved oral anticoagulation stability during follow-up showed, at the end of the study, significantly higher HRQoL scores. No interaction of HRQoL scores was observed between the presence of bleeding and treatment adherence. These findings corroborate previous data indicating that anticoagulated patients under multidisciplinary follow-up in specialized clinics can improve HRQoL.10,11
Recently our group published the results of a randomized clinical trial which evaluated the role of changes in dietary vitamin K intake in the management of chronic oral anticoagulation instability (patients with minor changes of INR).7 In this study we found that patients who were managed with predefined modifications in oral vitamin K intake were more likely to reach the desired target INR when compared to the conventional management (increases and decreases in oral anticoagulant dose). These results substantiate the interaction between dietary vitamin K and the effect of coumarin derived anticoagulants, and indicate that this strategy is feasible, safe and efficacious. However, such an approach could theoretically impact HRQoL in different ways. If oral anticoagulation stability could be more easily achieved over time, patients would suffer less adverse events and need less frequent blood controls, impacting positively on HRQoL scores. On the other hand, active changes in dietary patterns can be potentially troublesome for many patients. The dietary recommendations defined by the suggested protocol could be perceived as a major interference in routine food ingestion and impact negatively on HRQoL parameters. Our results indicate that the final net effect of both strategies (conventional adjustment and dietary adjustment) on the Duke Anticoagulation Satisfaction Scale overall score was similar over time. The lack of greater improvement in HRQoL parameters in the dietary adjustment strategy could be attributed, in part, to the relatively short period of follow-up during the protocol, besides the pre-specified blood drawings for INR measurement which were part of the original research protocol.
Qualitative studies have confirmed that frequent monitoring of blood tests and visits to the clinic, anxiety related to adverse events, patient autonomy, alcoholic and dietary restrictions and the impact of anticoagulant medication on physical activities have a negative impact on the HRQoL.12-14 Lancaster15 in a randomized clinical trial carefully analyzed the impact of long-term warfarin therapy in the HRQoL. This study randomized patients with non-rheumatic atrial fibrillation to warfarin treatment versus conventional management without anticoagulants. Patients were observed for two years and regularly had their HRQoL evaluated with validated scales which measure functional status, to "feel good" and health perception. Overall, there was no significant difference in measures of HRQoL between groups of patients treated with warfarin or not. However, patients with a bleeding episode had a significant reduction in perceived health.
Interestingly, some investigators have suggested that there is no association between oral anticoagulation stability and HRQoL, as demonstrated by Davis et al.6 In their study, anticoagulated patients with the worst perception of their HRQoL did not have worse stability of oral anticoagulation. However, this study had a relatively small sample size, and used a simple non-validated instrument to evaluate HRQoL (the 4-item Morisky survey). Recent studies indicate that patients under an oral anticoagulation self-management strategy using portable devices (Point of Care CoaguChek) to measure INRs also have better stability of oral anticoagulation, less bleeding episodes and improved HRQoL.16-18 In a randomized clinical trial comparing self-management strategy versus laboratory monitoring in which researchers used the Duke Anticoagulation Satisfaction Scale instrument, the results were similar to those obtained in the present study regarding the magnitude of HRQoL score variation, and better scores for HRQoL were found in patients with self-management of oral anticoagulation.19
In a randomized study of INR self-control versus conventional INR control there were significant improvements in HRQoL for patients in the domains of self-satisfaction and self-efficacy. Similarly to our findings, INR stability was associated with higher HRQoL in this last report.20
A potential limitation of the present study is that we used an instrument to evaluate quality of life related to health-specific anti-coagulated patients. This can be an advantage to capture changes in health status over time, but on the other hand, does not assess the broader areas which could also be affected by a chronic condition or by specific interventions. Casais et al.4 evaluated HRQoL of anticoagulated patients using the Medical Outcomes Survey 36-ltem Short Form (SF-36),21 considered to be a generic instrument for assessing HRQoL. They found that anticoagulated patients with more negative perceptions about their treatment achieved the lowest score in the SF-36 survey (which means the worst HRQoL). This instrument includes eight domains, including pain, general health and social aspects which are not included in the Duke Anticoagulation Satisfaction Scale, and may also have been affected by the type of management adopted for anticoagulation therapy.
This study showed that both strategies for oral anticoagulation improved HRQoL scores. Treatment guided by vitamin K in the diet did not substantially alter the improvement observed in the conventional treatment. Importantly, oral anticoagulation stability was directly associated with improvement in HRQoL scores, reinforcing the need to strengthen the efforts being made to pursue INRs within the therapeutic target.
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Eneida Rejane Rabelo
Escola de Enfermagem da Universidade Federal do Rio Grande do Sul
Rua São Manoel, 963. Bairro Rio Branco
90-620110 Porto Alegre. Rio Grande do Sul. Brazil
1.a Revisión: 13-III-2012