Adherence To Antihypertensive Medications Among Primary Care Centre Attendees in Trinidad: A Cross - Sectional Study

Objective: To determine the adherence levels to antihypertensive medications and its associated factors among primary care attendees in Trinidad. Methods: A cross - sectional study was carried out whereby an interviewer - administered questionnaire was administered to public primary care attendees throughout Trinidad. Non - pregnant hypertensive adults, attending chronic disease clinic on anti - hypertensive medications for at least 1 year were eligible. Results: Of 225 participants (92% response rate), 58% displayed a low level of adherence to anti - hypertensive medications and 73.3% had uncontrolled hypertension, both independent of age, gender and ethnicity. Experiencing adverse effects to prescribed medications (P=0.003) and self - reported use of herbal/alternative treatment (P=0.024) for hypertension were significantly associated with higher rates of low adherence. Having too many pills to take and fear about the potential effects of these medications on the body were both correlated with low adherence (P< 0.001) Obtaining antihypertensive medications from a national chronic disease assistance program was inversely correlated with low adherence (P= 0.03). There were no statistically significant associations between adherence and average systolic blood pressure (P= 0.20), home self - monitoring (P= 0.75), daily dosing frequency (P= 0.53) or daily number of pills (P= 0.68) Conclusion: Most primary care hypertensive patients who attended chronic disease clinics at primary care health centers around Trinidad were found to have uncontrolled hypertension along with low adherence to antihypertensive medications. Education, screening for herbal use and improvements to the existing national medication program, are discussed as interventions to improve adherence in this setting.


INTRODUCTION
Hypertension is one of the most common chronic diseases affecting greater than 1 billion people globally according to the WHO. 1 Hypertension is a major risk factor for both cardiovascular disease and cerebrovascular accidents.
Early diagnosis and effective treatment with antihypertensives are important to prevent significant morbidity and mortality in patients. 2 Adherence to prescribed antihypertensives is important in the effective management of hypertension. 3 Ensuring patient adherence to antihypertensives is a challenge due to a lack of patient education, adverse effects of medication, complex medication regimens and the need to continue treatment indefinitely due to the chronic nature of the disease. 4 Poor adherence to antihypertensive medications has been identified as one of the leading causes of failed treatment. 5 This subsequently leads to worsening uncontrolled hypertension which further predisposes the patient to various hypertension related comorbidities, cardiovascular and cerebrovascular events and frequent changes in medication regimens.
In Trinidad and Tobago, the prevalence of hypertension according to the Noncommunicable Disease Risk Factors Survey is approximately 26 percent. 6 Consequently, it is not surprising that the Pan American Health Organization has listed cardiovascular disease as the leading cause of mortality in Trinidad and Tobago. 7 There exist very few studies in our setting that have examined medication adherence in chronic disease management. Two studies performed in Trinidad have examined cardiovascular medication adherence and have reported an overall poor adherence to medication. 8,9 These studies, however, were conducted in cardiology secondary care settings. Most hypertensive patients however seek care at the primary care level and there has been a paucity of such surveys in this population. This study aims to determine the level of adherence to antihypertensives and associated risk factors in patients attending local health centers.

Study design, setting and sampling
This study was performed by utilising a cross-sectional study design and was conducted across primary care health centres in three of the four major Regional Health were also collected. The questionnaire was pilot tested before use to ensure that the necessary data were acquired and to ensure that its content and wording was appropriate. Questionnaires were administered via face-to -face interviews after written informed consent was obtained and blood pressure was measured on the day of the interview using a validated electronic monitor. The electronic monitors were calibrated, and the same monitors were used for all patients to ensure that all readings were standardized. Patients' charts were then CROSS-SECTIONAL STUDY accessed for the two most recent blood pressure readings and an average of all three readings was recorded.

Statistical analysis
Data were inputted and analysed using the statistical package for social sciences 24 (SPSS, Chicago, IL, USA).
Data was presented using descriptive statistics including means with standard deviations and proportions. Data were also analysed using chi squared testing for categorical and ordinal variables, and t-testing for comparison of means. Statistical significance was accepted at P< 0.05. Binary logistic regression analysis was employed to determine predictors of adherence.

Ethical Issues
Patients who participated in this study and were identified with elevated blood pressure and who were noncompliant were provided with their blood pressure readings and asked to visit their clinic or keep their follow up appointments. Similarly, patients who sought alternative treatment methods or experienced side effects were asked to relay this information to their usual primary care provider at the clinic. Permission was sought from the ethics committee of the University of the West Indies, St. Augustine and the participating RHAs before conducting the study. No proprietary or copyrighted instruments were used in this study. CROSS-SECTIONAL STUDY From our study it was found that the majority (58%) of the respondents had a low degree of adherence to antihypertensive medications. There were no statistically significant associations between adherence and age, gender, ethnicity, education or employment level as seen in  Table 2 Relationship between adherence levels and socio-demographic variables *ERHA-Eastern Regional Health Authority, NCRHA-North Central Regional Health Authority, NWRHA -North West

Demographics
Regional Health Authority Table 3 shows the predictors of low adherence.  Disagreement with statements "I am afraid to take my medicines because I do not know what they do to my body" and "I have too many tablets to take so I only take the ones I think work" were also associated with a reduced odds of low adherence.

CROSS-SECTIONAL STUDY Predictors of Low Adherence
Two factors, however, correlated significantly with an increased risk of low adherence. Experiencing side effects from blood pressure medications and use of herbal treatments for hypertension were each positively correlated with low adherence.
In further adjusted analyses the above associations persisted after inclusion of RHA in the logistic regression models. There were no associations (P values > 0.05) with specifically listed herbal remedies (garlic, lemongrass (fever grass), saffron, bitter melon (caraili) and spices) and low adherence. There were also no associations (all P values > 0.05) between adherence and side effects of fever, nausea, vomiting, diarrhea, headaches, cough, weakness, skin rashes and weight change. Of note there were no significant associations between adherence and blood pressure levels, self-monitoring at home, appointment times and access to clinic. Frequency, number of antihypertensives used daily, antihypertensive drug class and medication costs were also independent of adherence level. Self-reported comorbidities of stroke, heart attacks, renal disease and heart failure were also unrelated to adherence (P>0.05 for all non-significant relationships).

Blood pressure control and correlates
The mean duration of hypertension was 12.0 years (SD 9.8) while the average of the three most recent blood #Referent category for categorical independent variables. *Chronic disease assistance programme CROSS-SECTIONAL STUDY pressure readings was 151.5mmHg and 83.8mmHg for systolic and diastolic blood pressure respectively. Using

DISCUSSION
In this study, we focused on the prevalence and predictors of low adherence to antihypertensive medications in Trinidad. Adherence to antihypertensive medication is a problem both globally as well as in our population in Trinidad and Tobago as evidenced by two cardiovascular studies that were carried out in Trinidad which showed low to medium adherence of 75% and 78.3% respectively. 8,9,12 Patients who report strict adherence to their antihypertensive medication regimen have reported significantly lower systolic and diastolic blood pressure as compared to those patients who have ever reported a momentary lapse in adherence. 13 From our study, we found two-fifths of the patients were found to have high adherence to antihypertensives. While some countries have found adherence levels ranging from 44.8%-88.6%, [14][15][16] this low adherence level is in keeping with that highlighted in a 2017 meta-analysis. This review revealed an adherence level of 45.2% with 83.7% of those patients having uncontrolled hypertension. 17 The only demographic predictor of low adherence in this study was RHA. This may reflect differences in patient characteristics based on geography or variations in practice and medications accessibility based on region.
Non-adherence or poor adherence to antihypertensives has shown an increased risk for developing uncontrolled hypertension which subsequently increases the risk of cardiovascular mortality and strokes which then leads to an increase in hospitalization rates and cost of care. 18 However, in our study, there was no significant association between blood pressure greater than 140/90 and adherence level. Many variables apart from adherence may contribute to blood pressure control. Measurement techniques, inadequate or inappropriate drug therapy and secondary causes are some of these reasons. 19 A 2012 study that looked at adherence in over 1000 subjects concluded that only a small proportion of blood pressure variability can be explained by adherence. 20 From our study, we found that adverse effects to antihypertensive medications were a key factor associated with low adherence, a finding in keeping with other studies. [21][22][23] Patients taking multiple medications for their condition are also at an increased risk of non-adherence due to the complexity of their regimens and the increased likelihood of experiencing side effects in patients on polypharmacy. 24,25 This was in contrast to the findings of our study, however, which did not show associations between number of pills or frequency and adherence level.
Another significant factor that contributed significantly to low antihypertensive adherence in our study was the use of herbal or complementary alternative medicines (CAM).
One study found that CAM use resulted in decreased levels of adherence to antihypertensives amongst female participants while another study reported that older black adults who used CAM had lower levels of adherence to antihypertensives compared to their white counterparts. 14,26 Similarly, in our study CAM use was associated with low adherence. One particular alternative remedy that has been extremely popular amongst the global hypertensive population is the use of garlic. 27 Garlic was commonly used as an alternative remedy and we found that patients who used garlic in our study population had hypertension that was better controlled compared to non-users. A meta-analysis of 11 randomized control trials that was recently published showed that garlic was better at reducing blood pressure when compared to a placebo. 28 Garlic contains multiple active sulfur compounds leading to BP reduction via vasorelaxation. 29 In addition, we found that the use of garlic and its effect on hypertension was independent of adherence to antihypertensives. This finding was reported in other studies where patients tend to use CAM, in this CROSS-SECTIONAL STUDY case garlic, as a supplement rather than a replacement because they did not believe that CAM was better than conventional medication with one study showing that up to 79% believed that the use of both CAM and conventional medicine was superior when compared to using only one method. 30 We found that patients were more likely to be adherent to their prescribed drug regimen when they received assistance in obtaining medication through the Chronic Disease Assistance Program (CDAP). This was in comparison with patients who purchased their medicine.
CDAP is a program administered by the Government of Trinidad and Tobago that provides free chronic disease medication including antihypertensives. 31 The association between adherence and obtaining medications without costs has been highlighted by past reviews. 32  visits, personalized reminders via mail, telephone or email. 35 As such, we can start with patient education as the main methods of enforcing adherence by ensuring that patient understand how medications work and their associated side effects so that any negative effect they experience after starting medications will not be attributed to the medication. 22 In addition, physicians should make an attempt to simplify medication regimens where possible and attempt to not completely dismiss those patients who are interested in alternative remedies but instead ensure that the patient is adherent to their medication first and then allow them to continue use of their preferred alternative remedy once there are no side effects or drug interactions. 36

Strengths and Limitations.
The strengths of our study are that this is the first study of its kind to measure adherence in the hypertensive primary care population of our nation. Several noteworthy associations were found which has implications for interventions. Limitations of this study were its crosssectional nature and lack of causal inferences, and response bias. The participants selected by convenience at each clinic may not have been representative of all hypertensive patients even within each RHA. The original Morisky adherence tool used in this study has undergone refinements to better validated tools, namely MMAS4 and MMAS8, however the costs of institutional licenses for these tools were beyond the budget of this study. A better validated tool may have resulted in associations that this study failed to show. This study did not examine adherence in patients who sought care at the Southwest Regional Health Authority (SWRHA) or privatized settings.

Next steps
Future studies should measure adherence in the SWRHA and private sector. Variations in adherence by RHA and geographic locations also warrant further exploration.
With the launch of the TT Global Hearts Initiative it is also worth investigating its impact on adherence in the future to gauge its effectiveness and patient acceptance.
Research into patient education and knowledge of hypertension may also reveal a gap making room for educational interventions regarding antihypertensive medications, mechanism of action, side effects and herbal misuse. Enhancement of the existing CDAP with newer agents may also improve access and adherence, and blood pressure control.

CROSS-SECTIONAL STUDY CONCLUSIONS
Adherence to antihypertensive medications in the study population was found to be very low. We were able to identify several factors that may explain the variation in adherence level with antihypertensives in this survey.