Compliance of patients after prosthetics mitral double valve mechanical prostheses

Introduction

Patients who have undergone mitral valve (MV) replacement with mechanical prostheses need lifelong treatment with oral anticoagulation therapy [1][2]. For many years, warfarin has been the medicine of choice. Timely anticoagulation treatment helps to prevent serious postoperative complications and thereby increases the survival rate and quality of life of patients. On the other hand, the narrow therapeutic index of warfarin dictates the need to regularly monitor and adjust the doses of the medicine [3][4].

According to research, an important factor for effective anticoagulant therapy is patient compliance (commitment to treatment). Compliance is defined as the degree to which a patient voluntarily integrates into cooperation with a doctor regarding medication intake (dosage, timing, and frequency of medication) and other medical appointments. It is proved that on average, 20% of patients constantly poorly control anticoagulant therapy [5][6].

The study of compliance has been the subject of interest and discussion of clinicians and researchers for many years, since the degree of a patient’s adherence to treatment is closely interrelated with the effectiveness of treatment and prognosis. At the same time, the important aspects of compliance being studied are the factors influencing it both from the patient's side and from the doctor's side, and the search for ways to improve the degree of compliance [7-9].

The purpose of the study is to study such factors as gender, age, family status, level of education, and the multiplicity of the definition of the international normalized relationship (INR) and compare their impact on the compliance of patients after prosthetics with mechanical prostheses in dynamics (after 6 and 12 months).

Materials and methods

The retrospective study included data from 260 patients operated at the Federal State Budgetary Institution "Federal Center for Cardiovascular Surgery" (Astrakhan). All the patients underwent surgical intervention – isolated MC prosthetics with mechanical double-leaf prostheses. The data collection period was 2012–2014.

The conducted research complied with the provisions of the Helsinki Declaration and was approved by the local ethics committee.

Among the examined 260 patients, there were 84 (32.3%) men, 176 (67.7%) women. The age of the examined was 49.3±8.7 years. The dominant etiological factor of the MV lesion was chronic rheumatic heart disease. It caused the formation of mitral malformation in 207 patients (79.6%). The myxomatous lesion led to the development of mitral malformation in 36 patients (13.9%). The rarest cause of mitral malformation was infectious endocarditis in 17 patients (6.5%).

During the study, some patients were censored, and some died. The number and characteristics of patients depending on the study period are presented in Table 1.

Since the analyzed sample of patients is related, at the 6-month stage, the authors evaluated compliance in 221 patients, and at the 12-month stage – in 212, excluding patients who dropped out during the period of 6–12 months.

All the patients were prescribed anticoagulant therapy with the indirect anticoagulant warfarin by the time of discharge. Patients were recommended to maintain INR in the range of 2.5–3.5 with monthly monitoring of the coagulation index.

The Morisky-Green test (4-item Morisky Medicine Adherence Scale – MMAS-4) was used to assess compliance [10]. This test contains the following questions:

1. Have you ever forgotten to take medications?
2. Do you sometimes not pay attention to the hours of taking medications?
3. Do you skip taking medications if you feel well?
4. If you feel unwell after taking medications, do you skip the next appointment?

Each question was asked to give a positive or negative answer (yes/no). Each negative answer on the Morisky-Green test is estimated at 1 point. Patients who scored 4 points are considered committed to therapy, 1–2 points – not committed to therapy, 3 points – insufficiently committed with the risk of switching to the group not committed to treatment. In the present study, patients who scored 3 or more points were considered compliant/committed to therapy, and those who scored less than 3 points were considered incompetent.

The survey of patients was conducted in writing by means of a questionnaire, as well as by phone and during an examination at the clinic.

The patients were divided into age groups according to the latest WHO age classification: young age – 18–44 years, average age – 45–59 years, elderly age – 60–74 years.

Statistical analysis was carried out using the StatTech v. 1.2.0 program (developed by Stattech LLC, Russia). Categorical data were described with absolute values and percentages. The comparison of percentages in the analysis of four-field and multi-field conjugacy tables was performed using the exact Fisher criterion. As a quantitative measure of the effect when comparing relative indicators, an indicator of the odds ratio with a confidence interval of 95% (OR; 95% CI) was used. The differences in the indicators were statistically significant at p <0.05.

Results

In the postoperative period after 6 months, 158 patients out of 221 were compliant, which was 71.5% of the examined. The number of compliant patients was 2.6 times more than the number of non-compliant patients.

According to the data presented in the literature, compliance depends on many factors. The authors have attempted to study the relationship of compliance with such factors as gender, age, marital status, level of education, and the multiplicity of the definition of INR.

When analyzing compliance depending on gender, statistically significant differences were found – p=0.043 (Table 1).

There were 73.2% of compliant patients among females versus 68.1% among males. At the same time, belonging to the female sex increased the chances of being compliant by 1.28 times (95% CI 0.69–2.38). A relatively strong relationship was noted between the compared signs (V=0.43).

As can be seen from the data presented in Table 2, when analyzing compliance depending on age, statistically significant differences were obtained (p=0.007), a posteriori comparisons also showed statistically significant differences (p=0.019) (Table 3).

The percentage of compliant patients in the middle-aged group prevailed in comparison with young and elderly people. Thus, among middle-aged patients, 78.3% were compliant, which was statistically significantly higher compared to young and elderly people, where the percentage of compliant patients was 61.3% and 50%, respectively.

When assessing compliance, depending on marital status, it was found that there was a greater adherence to prescribed treatment in a subgroup of married people (p=0.01) (Table 4).

Among married patients, adherence to treatment was noted in 78.2%, and in the unmarried subgroup – 62.9%. The chance of being compliant in married people increased by 2.12 times (95% CI 1.17–3.84). At the same time, there was a weak relationship between the compared signs (V=0.17).

Statistically significant (p=0.038) differences in the compliance analysis were also revealed depending on the level of education of the examined patients (Table 5).

Thus, among those with secondary education, 46.7% were compliant, and 71% with secondary special education. Among people with higher education, 80.4% were compliant, which was statistically significantly higher compared to people with secondary education (p=0.03).

It seemed interesting to determine the relationship of compliance according to the results of the Morisky-Green test with the multiplicity of INR determination as another characteristic of accurate adherence to medical recommendations. The data obtained are presented in Table 6.

According to the table presented, statistically significant differences (p <0.001) were found in the compliance analysis 6 months after the operation, depending on the multiplicity of INR determination.

The number of compliant patients among those who monitored INR monthly was statistically significantly higher (p <0.001) compared to patients where this indicator was determined less than once a month – 75.3% vs. 21.5%. Among the uncontrolled INR, there were 3.2% of compliant patients. At the same time, the percentage of patients who did not control ME after 6 months was 10%.

At the last stage of the study, the authors analyzed the dynamics of compliance 12 months after surgery, taking into account the analyzed factors. The analysis showed that the decrease in compliance for 12 months after surgery was statistically significant among both female and male persons, married and unmarried (Table 7).

There was a statistically significant decrease in the number of compliant patients in the groups of young and middle-aged people. Compliance also decreased among the elderly, but the dynamics were not statistically significant. A statistically significant decrease in the number of patients committed to treatment was also observed in subgroups with secondary specialized and higher education. The analysis of the dynamics of compliance and the multiplicity of INR control after 12 months of follow-up compared with 6 months of follow-up revealed a statistically significant decrease in compliant patients both among persons controlling INR 1 time per month and among persons controlling INR less than 1 time per month.

With a continuing trend in the frequency of occurrence of compliant patients after 12 months, when separating them depending on gender, age, marital status, and level of education, statistically significant differences were revealed only when analyzing compliance depending on marital status: the percentage of compliant patients was higher among married persons (p <0.001) and depending on the multiplicity INR control (p <0.001).

Discussion

Different studies of compliance and the factors influencing it are certainly of high practical importance. Predictors of adherence to warfarin treatment in the postoperative period in patients who have undergone the replacement of MV with mechanical prostheses, according to domestic and foreign studies, are diverse, but often contradictory. On the part of patients, factors that may affect the effectiveness of warfarin therapy include age, nutrition, gender, education, weight gain/loss, alcohol consumption, concomitant diseases, etc. Therefore, according to Ragab et al., it was concluded that the female sex adhered better to the recommendations for warfarin therapy than the male sex [11]. Another important predictor of treatment adherence is the patient's level of education. Even in a number of studies, older age groups were significantly unaware of most aspects of anticoagulant therapy [12, 13], which, according to Hasan et al., is associated with a decrease in cognitive abilities [14]. It was proved (Kaya et al.) that a lower level of education seemed to be associated with poor anticoagulant therapy of knowledge [15]. According to Thomson Mangnall et al., it was found that elderly people had a low level of education and lack of professional knowledge, which significantly reduced adherence to warfarin treatment [16]. Also, according to the authors, young age was statistically significantly associated with non-compliance with the warfarin therapy regimen. At the same time, Platt et al. did not find an association between adherence to warfarin treatment with age and gender [17]. In the studies by Wang and Shilbayeh, no significant relationship was established between education and adherence to warfarin treatment [18, 4].

The authors of this particular study found that the most committed to treatment after undergoing the operation of prosthetics of MV were female, middle-aged, with secondary specialized and higher education, as well as married people. At the same time, belonging to the female sex increased the chances of being compliant by 1.28 times, and the chance of being compliant for married people increased by 2.12 times. Among the patients who monitored INR monthly, the percentage of compliant patients was statistically significantly higher compared to patients where this indicator was determined less than once a month (p <0.001). This seems logical, since a responsible attitude toward drug therapy and its control are interrelated links in a single patient management process. The presence of persons among compliant patients who did not comply with the recommended INR control regime underlines the fact that the Morisky Green test, although validated and reliable, still does not take into account all aspects of compliance, but only those related to patients' adherence to prescribed medications. The concept of "compliance" in a broad sense also implies the implementation of non-drug lifestyle recommendations and laboratory monitoring of significant indicators.

While analyzing the dynamics of compliance depending on gender, age, marital status, and the level of education after 12 months of follow-up compared with 6 months of follow-up, a statistically significant decrease in adherence to treatment was found by the end of the first year of patient follow-up. This pattern was observed both among women and men, mainly among young and middle-aged people, in patients with secondary, specialized secondary, and higher education, as well as in persons who were and were not married.

While analyzing the dynamics of compliance and the multiplicity of INR control after 12 months of follow-up compared to 6 months of follow-up, attention was drawn to the fact that a statistically significant decrease in compliance was noted not only among persons who controlled INR less than 1 time per month but also among those who did it in accordance with the recommendations 1 time per month.

Conclusion

The data obtained by the authors of this particular study indicate the need to carry out more active work on the formation of compliance with "vulnerable" categories of patients: men, elderly and young patients, persons with secondary education, and unmarried. The revealed tendency to decrease compliance after 12 months among all examined patients, regardless of the studied factor, indicates the importance of "time elapsed after surgery" as one of the leading factors affecting the degree of compliance, which is able to offset the impact of factors such as gender, age, marital status, and education level. This, in turn, indicates the importance of maintaining patients' adherence to prescribed treatment in the long-term postoperative period. At the same time, it should be noted that among all the analyzed factors, after 12 months, despite the decrease in the percentage of compliant patients, the frequency of occurrence of such was statistically significantly higher only in patients who were married compared with patients outside of marriage. Also, the data obtained indicate the presence of a relationship between the multiplicity of INR control and compliance.