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Factors associated with antihypertensive drug compliance in 83 884 Chinese patients: a cohort study
  1. M C S Wong,
  2. J Y Jiang,
  3. S M Griffiths
  1. School of Public Health, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region, China
  1. Correspondence to Johnny Y Jiang, School of Public Health, Prince of Wales Hospital, 4/F, Shatin, NT, Hong Kong, China; jiangyu{at}cuhk.edu.hk

Abstract

Background Few studies address the profiles of antihypertensive compliance among ethnic Chinese. The levels of and factors associated with antihypertensive drug compliance among Chinese patients were evaluated in this study.

Methods All Chinese hypertensive patients who paid at least two consecutive visits in any government primary care clinics for antihypertensive drug refill in a large territory of Hong Kong from January 2004 to June 2007 were included. Medication possession ratio (MPR), defined as the ratio of total days of medication supplied (not including the last prescription) to total days in a period of time, was used a measure of drug compliance.

Results From 83 884 eligible patients, 71 685 (85.5%) had good compliance to antihypertensive drugs (MPR ≥80%). Binary logistic regression analysis was conducted, with good compliance as the outcome variable while controlling for potential confounders. Advanced age (adjusted ORs (aOR) 1.36–1.55, p<0.001), female gender (aOR for male patients 0.84, 95% CI 0.80 to 0.87, p<0.001), payment of fees (aOR 1.14, 95% CI 1.09 to 1.19, p<0.001), attendance in family medicine specialist clinic (aOR 1.52, 95% CI 1.40 to 1.66, p<0.001), follow-up visits (aOR 3.21, 95% CI 3.06 to 3.36, p<0.001) and use of drugs acting on the renin–angiotensin system (aOR 1.18, 95% CI 1.07 to 1.30, p=0.001) were positively associated with good compliance to drugs. Use of β-blockers was negatively associated with drug compliance (aOR 0.78, 95% CI 0.73 to 0.84, p<0.001).

Conclusions Physicians should practice caution when prescribing antihypertensive drugs to patients with these factors where closer monitoring of their compliance patterns is warranted.

  • Antihypertensive drugs
  • compliance
  • associated factors
  • Chinese
  • ethnicity
  • clinical pharmacology
  • hypertension
  • pharmacoepidemiology

https://doi.org/10.1136/jech.2009.091603

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    Introduction

    Worldwide, the prevalence of hypertension is 26% of the adult population,1 estimated to be responsible for 4.5% of the disease burden, or 64 million disability-adjusted life years. It affects 1 billion individuals, attributing to 7.1 million deaths per year.2 There is an increasing incidence in many developed countries and has been identified as the leading risk factor for mortality.1

    While persistent use of antihypertensive agents has been proven effective to reduce the burden of hypertension,3 4 only 30% of patients in Caucasian countries with hypertension reach their target blood pressure goals.5 Similarly poor or even worse rates of adequate control have been noted worldwide, including European and Asian countries.5 6 Among patients who have poor blood pressure control, half could be attributed to suboptimal drug compliance.7 8 A recent study reported low levels of antihypertensive compliance among elderly patients in the USA, Canada and the Netherlands, and concluded that the problems of antihypertensive non-compliance transcend international boundaries.9 Poor drug compliance is one of the causes for refractory hypertension,10 and accounts for substantial worsening of disease, death and increased healthcare costs.11 12 Also, it has been shown that initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive drugs.13

    Efforts to quantify antihypertensive drug compliance are essential,1 and addressing the factors associated with antihypertensive drug compliance could provide clinicians and policy makers with targets to intervene and improve medication persistence.9 Many studies have addressed these factors among Caucasian populations.14–16 However, there is a scarcity of studies evaluating these factors among Chinese patients,17 and it is well recognised that different cultural attitudes about healthcare could influence medication-taking behaviour.9 For instance, antihypertensive drug compliance was found to be lower in non-Caucasians than in Caucasians.18 19 Chinese people represent more than one-fifth of the world's population and reside in different parts of the world, and thus far it is unknown whether the factors determining good antihypertensive compliance is generalisable to patients of Chinese ethnicity.

    This study aims to examine the factors associated with antihypertensive compliance in Chinese patients. We tested the hypothesis that younger age, female gender and use of drugs acting on the renin–angiotensin system (RAS) were independent predictors of good drug compliance, as reported from a recent cohort study including patients from the USA, Canada and the Netherlands.9

    Methods

    Data source

    The Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong, consists of all patient records in public clinic visits since 2000. It captures patients' demographics, clinical information including diagnoses, prescription details and laboratory investigation results in every outpatient consultation. One of the major functions of Clinical Data Analysis and Reporting System is research.20 It is the single portal of information entry in the public sector and is a comprehensive record that allows cross-referencing when patients visit a different clinic. Also, drug prescription details are doubly checked by pharmacist professionals, and any amendments were recorded in the electronic patient record. In addition to these good practices, this database has been evaluated and found to have a high level of completeness with respect to demographic data (100%) and prescription details (99.98%).21 The present study included Hong Kong residents in the New Territory East Cluster, which has a population of around 1.3 million. It is further divided into three separate regions, namely Shatin, Tai-Po and the North District, from the most urbanised to the most rural regions, respectively. Their median monthly household incomes in 2006 were comparable to the Hong Kong-wide figure of US$2240. These three regions have similar median ages (38–39 years), comparable with the median age of 39 years for Hong Kong.22 This study was approved by the Hospital Authority and the Surveys and Behavioural Research Ethics Committee, Chinese University of Hong Kong.

    Subjects

    From the database, patients who attended the public primary care practice and received a single antihypertensive prescription in the public sector during January 2004–June 2007 were included. We excluded patients who had paid only one clinic visit where antihypertensive drugs were prescribed, since drug compliance could only be assessed for patients who went to the clinic at least twice for antihypertensive medications. The maximum duration of the prescriptions recorded was 27 weeks from all the prescriptions, and there was no restriction on the length of prescription as our subject inclusion criteria. Each patient was classified into one drug group according to the prescription. These include β-blockers, thiazide diuretics, calcium channel blockers, drugs acting on RAS and others (including α-blockers, potassium-sparing and other diuretics, vasodilators and combination treatment). Patient comorbidities include concomitant cardiovascular risk factors and medical conditions confounding the initial antihypertensive drug choice other than uncomplicated hypertension,20 as indicated by the respective International Classification of Primary Care (ICPC-2) code.

    Outcomes variables and covariates

    The outcome variable is the measure of drug compliance represented by the medication possession ratios (MPR), an accepted metric for the evaluation of compliance using retrospective data.23 It is defined as the ratio of total days of medication supplied by the number of prescribed pills (not including the last prescription) to total days in a period of time.24 MPR is a dichotomous variable with values ≥80% considered compliant.25 26

    The independent variables that we controlled for include patients' age, gender, payment status (fee waivers vs fee payers; each consultation costs US$5.77, including investigation and prescription fees), district of residence, clinic types visited (general outpatient clinic vs family medicine specialist clinic vs staff clinic), visit type (new vs follow-up visit), the number of comorbidities and the antihypertensive drug class prescribed. New visitors were patients who paid their first clinic visit during the study period January 2004–June 2007, while follow-up visitors paid their first visit before the study period and attended at least once within this period.

    Statistical analysis

    The Statistical Package for Social Sciences version 15.0 (SPSS, Inc) was used for all data analysis. For descriptive analysis, Student's t tests and χ2 tests were used to compare continuous and categorical variables, respectively. In multivariate analyses, we entered all the variables listed above into a binary logistic regression model with good antihypertensive compliance (MPR ≥80%) as the outcome variable. We further stratified all patients by their gender and age groups (<50, 50–59, 60–69, ≥70 years) and performed separate binary logistic regression analyses for each subgroup. We conducted sensitivity analyses where each antihypertensive drug class was used as the reference group in the regression equations consecutively to detect any differences. All p values <0.05 were regarded as statistically significant.

    Results

    Patient characteristics

    From 93 353 patients, 9469 (10.1%) paid only one visit and were excluded from the analysis. There were 83 884 eligible patients with a mean age of 64.25 years (95% CI 64.16 to 64.34). The majority of them were female patients (57.2%), fee payers (73.9%), attended general outpatient clinic (90.7%) and lived in urbanised regions (71.3%) (table 1). New visitors accounted for more than half of all patients, and most patients had no comorbidities apart from hypertension (71.5%). Among the major antihypertensive drug classes, calcium channel blockers (24.0%) and β-blockers (19.0%) were most frequently prescribed (table 1). The crude proportion of patients having good compliance was 85.5%, and this figure was much lower among new visitors (79.1%) than follow-up visitors (92.9%) (table 2). The mean interval between two clinic visits was 63.9 days (SD 76.4). The mean observation time of patients was 63.9 days (SD 76.4), and the mean persistence time was 49.8 days (SD 3.95).

    View this table:
    Table 1

    Patient characteristics (N=83 884)

    View this table:
    Table 2

    Factors associated with compliance to antihypertensive drugs (N=83 884, r2=0.083)

    The characteristics of patients who visited only once and patients who paid at least two visits for antihypertensive drug refill were different. When compared with visitors who paid at least two visits for antihypertensive drug refill, significantly more patients who visited only once were younger (26.8% vs 14.4% were aged <50 years), male patients (46.2% vs 42.8%), fee waivers (31.4% vs 26.1%), attendees of staff clinics (1.3% vs 0.3%), new visitors (76.9% vs 54.0%), had no concomitant comorbidities (84.4% vs 71.5%), and users of β-blockers (34.4% vs 19.0%) and RAS (8.6% vs 7.6%) (all p<0.001). Significantly less patients who visited only once lived in urbanised region (Shatin and Taipo; 71.3% vs 67.8%, p<0.001). In addition, 76.9% of patients with only one visit were patients newly diagnosed as having hypertension.

    Factors associated with antihypertensive drug compliance

    From multivariable regression analyses, patient age of 50 years or older, female gender, payment of fees, attendance in family medicine specialist clinic, and follow-up visits were positively associated with good compliance to antihypertensive medications (table 2). When thiazide diuretic was used as a reference group, users of β-blockers were negatively associated with drug compliance while users of drugs acting on RAS were positively associated with drug compliance. The district of residence and number of comorbidities were not significant factors associated with drug compliance (table 2).

    Regarding the goodness of fit, the Nagelkerke R2 is 0.083, indicating that these factors accounted for 8.3% of the variability of the outcome variable.

    Gender-specific factors associated with drug compliance

    When patients were stratified into male and female groups and analysed separately by multivariable regression analyses, advanced age, payment of fees, attendance in family medicine specialist clinic, follow-up visits, and use of RAS were associated with drug compliance (table 3). Users of β-blockers remained less likely than other drug classes to have good compliance. Residence in more rural areas and the presence of one comorbidity were significantly associated with drug compliance among female patients but the respective 95% CIs overlapped with those among male patients (table 3).

    View this table:
    Table 3

    Factors associated with compliance to antihypertensive drugs by gender

    Age-specific factors associated with drug compliance

    The factors associated with drug compliance were similarly observed when patients were divided into different age groups (table 4). The magnitudes of the respective ORs were statistically similar, with two exceptions. Patients having one comorbidity were significantly more likely to have drug compliance only among the younger age groups (<50 years; 50–59 years). In addition, users of β-blockers were statistically significantly less likely to have drug compliance among the younger age groups but not among the elder patients (table 4).

    View this table:
    Table 4

    Factors associated with compliance to antihypertensive drugs by age groups

    Use of each antihypertensive drug class as the reference group consecutively in all regression equations revealed similar results on the association of drug class with drug compliance (results not shown).

    Discussion

    Major findings

    The present study evaluated the factors associated with antihypertensive drug compliance. The overall rate of good antihypertensive drug compliance was high (85.5%) compared with other studies. Advanced age, female gender, payment of fees, visits in family medicine specialist settings, follow-up visits, and use of RAS were positively associated with good compliance to antihypertensive treatments. Female or younger patients having only one comorbidity had better drug compliance. Compared with users of other antihypertensive drug classes, users of β-blockers were less likely to be compliant especially among younger patients. Furthermore, comorbidities and district of residence were not related to compliance of antihypertensive drugs.

    Relationship to literatures

    The overall proportion of antihypertensive compliance was only 79.1% among new visitors, lower than the adherence rate of 88–90% among US veterans newly diagnosed as having hypertension from the electronic records of the Central Texas Veterans Health Care System and the Veterans Affairs healthcare system.27 28 Nevertheless, as pointed out by Vincze et al,27 electronic monitoring studies reported a wide range of medication adherence from 63% to 91%,29 and other studies reported rates ranging from 53% to 85% among hypertensive patients.30 The level of compliance depends on many factors, including problems with physicians, patients and the treatment.31

    The findings of this study were compatible with the majority of studies that reported better adherence to antihypertensive agents among older individuals than younger patients.32 For instance, a US managed care database found that improved MPR, a measure of drug compliance, was correlated with increasing age.33 Findings from the 2003 California Health Interview Survey, a population-based telephone random-digit-dial telephone survey of California households, reported that older age was associated with better self-reported antihypertensive drug compliance.34 Similarly, pharmacy claims data from the Maryland Medicaid patients found that those younger than 40 years were significantly less likely to be compliant than patients older than 60 years.35

    Similarly, most studies found that women tend to adhere better in comparison to men,36 37 although conflicting data exist about adherence rates among male and female patients.32 Turning to service settings, patients who attended family medicine specialist clinic were more likely to be compliant. It has been recognised that stronger patient–provider relationship and patient involvement with their treatment decisions were adherence facilitators.32 Therefore, one explanation for this could be the presence of more family medicine specialists and longer consultation hours for each patient in family medicine specialist clinic, thus providing better opportunities to offer advice on drug compliance.

    In addition, follow-up visitors were more likely to be compliant when compared with new visitors, and previous literatures have reported that antihypertensive persistence may be as low as 45% for newly diagnosed patients32 38 This may be attributed to relatively insufficient knowledge and negative beliefs about hypertension and its treatment among new visitors, as they were likely to be antihypertensive drug naïve. These have been recognised as patient barriers to antihypertensive adherence.32

    This study consistently reported poorer compliance profiles of β-blockers in age- and gender-specific analyses especially among younger patients. Other studies analysing compliance profiles in different patient populations also reported similar findings.28 39 However, studies among Chinese patients revealed that prevalence of side effects among β-blocker users was lowest among all drug classes,36 and that β-blockers should be less efficacious among elderly patients due to their low-renin status.40 It was therefore possible that other factors come into play, including complexities of drug regimens and physicians' negative perceptions on β-blockers as a monotherapy for management of hypertension.31 In addition, the pharmacological action of β-blockers might differ in patients of different populations due to variations in hepatic metabolism.24 The lower drug compliance of β-blocker users compared with thiazide users may also be due to adverse effects of β-blockers, while low side effects and once-daily dosing schedule of RAS should achieve improvements in compliance.

    It remains unknown why patients with one comorbidity had better drug compliance among female or young patients. Multiple chronic conditions have been recognised as an adherence facilitator,32 but patients with more than one comorbidity had similar odds of compliance with patients having no comorbidities. The relationship between comorbidity and antihypertensive drug compliance among Chinese patients remained to be explored.

    Implications to clinical practice and healthcare policy

    To our knowledge, this is the first study in the Asia Pacific region of this scale that evaluated the factors associated with antihypertensive drug compliance among ethnic Chinese patients. It constitutes a real-world insight into the compliance profiles in a large Chinese cohort. The demographic similarity of our study subjects' with the whole population of Hong Kong and the robust sample size allows the generalisation to Chinese patients to be more convincing. The implications were clear to physicians and policy makers—that patients with these associated factors should have more meticulous monitoring of their drug compliance, and that this is especially important for newly diagnosed patients, who have the highest odds of antihypertensive non-compliance (adjusted OR 3.21, 95% CI 3.06 to 3.36). This could be achieved by involving patients in decision making about treatment,41 reinforcement of home blood pressure monitoring,42 simplifying drug regimens to once-a-day dosing, organising healthcare to provide easy access to health professionals, and sending reminders about appointments and continued compliance to medications.41

    Study limitations

    Our study subjects were from one territory of Hong Kong, the population characteristics of which were different from China, hence limiting its generalisability. Another important limitation of this study is the assumption in assessing medication compliance through pharmacy data—that is, that when patients refill their prescriptions, they are taking their treatments on a regular basis. However, MPR is a recognised acceptable metric in evaluation of antihypertensive drug compliance.23 In addition, we studied compliance using drug refill patterns in two consecutive consultations; longer-term compliance profiles and the reasons of medication non-compliance cannot be assessed. Subsequent drug discontinuation and switching patterns could influence MPR, and this should be interpreted with recent studies on antihypertensive discontinuations.43–46 Finally, many factors have been known to influence antihypertensive drug compliance, including stages of hypertension, educational levels, side effects of medications, as well as patients' perceptions, beliefs and behaviour,31 and these could not be assessed by our database study.

    Perspectives

    In conclusion, many of the factors associated with antihypertensive drug compliance among Chinese patients were similar to those identified by studies conducted in Caucasian populations. However, there were still some prominent differences, namely the lower likelihood of compliance among β-blocker users and the effect of comorbidities on antihypertensive compliance, which could possibly be explained by ethnic differences. This is substantiated by recent studies by Li et al24 40 highlighting that cultural health perceptions and cultural healthcare activities are important constructs in determining antihypertensive drug compliance. Since studies on antihypertensive drug compliance were scarce among ethnic Chinese, more should be conducted to identify various facilitators and barriers to compliance in this ethnic group.

    What is already known on this subject

    • Non-compliance to antihypertensive drugs remained high worldwide.

    • There is a scarcity of studies evaluating the factors associated with antihypertensive drug compliance among ethnic Chinese patients.

    What this study adds

    • From 83 884 Chinese patients prescribed an antihypertensive agent and who paid at least two consecutive visits in primary care clinics, 85.5% had good compliance to antihypertensive drugs.

    • Advanced age, female gender, payment of fees, attendance in family medicine specialist clinic, follow-up visits, and use of drugs acting on the renin–angiotensin system were positively associated with good compliance to drugs, while users of β-blockers were negatively associated with drug compliance.

    • Physicians should exercise close monitoring of their patients' compliance when prescribing antihypertensive drugs to those with these associated factors.

    Acknowledgments

    The authors would like to acknowledge the support of the Hospital Authority, Hong Kong, and the input by colleagues in the Primary Care Research Group of the School of Public Health, Chinese University of Hong Kong, for their generous support to this project.

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    Footnotes

    • Data access: All authors had full access to all study data and can take responsibility for the integrity of data and the accuracy of data analysis. Data Sharing: Technical appendix, statistical code and dataset are available from the corresponding author at jiangyu{at}cuhk.edu.hk

    • Competing interests None.

    • Ethical approval This study was approved by the Survey and Behavioural Research Ethics Committee, Faculty of Medicine, Chinese University of Hong Kong.

    • Provenance and peer review Not commissioned; externally peer reviewed.