Factors Associated With Antihypertensive Drug Discontinuation Among Chinese Patients: A Cohort Study

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1 nature publishing group Factors Associated With Antihypertensive Drug Discontinuation Among Chinese Patients: A Cohort Study Martin C.S. Wong 1, Johnny Y. Jiang 1, Trevor Gibbs 1 and Sian M. Griffiths 1 Background Antihypertensive drug discontinuation imposes a substantial health services burden but few studies have addressed the factors associated with their discontinuation in Chinese patients. This study evaluated the association between age, gender, and drug classes with antihypertensive discontinuation. Methods From clinical databases, we included all adult patients prescribed an antihypertensive medication during January 2004 to June 2007 in one large territory of Hong Kong. We studied the factors associated with drug discontinuation within 180 days after the first prescription date by multivariable regression analysis. Results From 93,286 eligible patients, 13.2% discontinued their antihypertensive prescriptions. Younger (<50 years; adjusted odds ratio (aor) = 0.63 for patients aged years; 0.52 for patients aged years; 0.70 for those aged 70 years; all P < 0.001) and It is well recognized that effective treatment of hypertension reduces morbidity and mortality, 1 3 given the persistent use of antihypertensive drugs. 4,5 Recent studies in United Kingdom 6 and Italy 7 showed that discontinuation rates of antihypertensive drugs were high among patients newly diagnosed with hypertension in the first 6 months (20.3%) (ref. 6) and 1 year (42.6%) (ref. 7) after treatment initiation; and these rates were substantially higher in actual clinical practice than in long-term clinical trials In addition, male gender, younger age, the presence of chronic diseases, and prescriptions of some antihypertensive drug classes like β-blockers and thiazide diuretics were significantly associated with drug discontinuation. 6,7 This imposes a substantial public health burden as a large proportion of health-care expenditure can be attributed to patients who discontinue antihypertensive therapies School of Public Health and Department of Community and Family Medicine, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong. Correspondence: Johnny Y. Jiang (jiangyu@cuhk.edu.hk) Received 1 December 2008; first decision 31 January 2009; accepted 14 March 2009; advance online publication 9 April doi: /ajh American Journal of Hypertension, Ltd. male patients (aor = 1.05, P = 0.027) were more likely to have drug discontinuation. When compared with thiazide diuretics, patients prescribed β-blockers were more likely (aor = 1.67, P < 0.001) and patients prescribed calcium channel blocker (CCB) (aor = 0.76, P < 0.001) and combination therapy (aor = 0.73, P < 0.001) were less likely to have drug discontinuation. Stratified analyses in different age and gender groups reported similar results; except that only elderly male patients (aor = 1.12, P = 0.002) and younger patients (aor = 2.43 for patients aged <50 years, P < 0.001) prescribed β-blocker were more likely to have drug discontinuation. Conclusions Discontinuation of antihypertensive drug treatment in ethnic Chinese is more likely to occur in younger, male patients, or those prescribed β-blockers. These data suggest that more meticulous monitoring of patient adherence is required in patients with these characteristics. Am J Hypertens 2009; 22: American Journal of Hypertension, Ltd. Many clinical trials and retrospective database studies have compared discontinuation rates among the major antihypertensive drug classes. However, these studies were conducted almost exclusively among Caucasian populations, and it is well known that the pharmacological effects of antihypertensive drugs differ in patients of different ethnicity. 12 Our recent study on Chinese hypertensive patients without other comorbidities from more than one million antihypertensive prescriptions has reported a significantly lower discontinuation incidence among users of thiazide diuretics and calcium channel blockers (CCBs) within 180 days, when compared with β-blockers and drugs acting on the renin angiotensin system. 13 Nevertheless, few studies have ever elucidated the factors associated with antihypertensive discontinuation, which could effectively inform physicians on their prescribing practice and identify patients requiring closer monitoring of their drug adherence. Addressing factors which are modifiable could potentially lead to improved patient adherence, 14 as well as large savings of public health resources. 11 The objective of this study is to evaluate the factors associated with antihypertensive discontinuation within 180 days of their prescription, with a particular focus to explore the 802 july 2009 VOLUME 22 NUMBER AMERICAN JOURNAL OF HYPERTENSION

2 Antihypertensive Discontinuation Among Chinese articles association between drug discontinuation and patients age, gender, as well as the antihypertensive classes used. Methods Source of data. The Hospital Authority of Hong Kong, which provides free or low-cost primary and secondary care as part of the public health-care sector, adopted a comprehensive computerized patient recording system in 2000, which captures patients clinical and demographic parameters, clinical diagnoses in terms of International Classification of Primary Care codes, types of clinical services (general outpatient vs. family medicine specialist clinic (FMSC) vs. staff clinics) as well as drug prescription details. This database thus far consists of seven million patient records, one million annual admissions, and 13 million ambulatory visits. The resultant databases set up by the Hospital Authority has research as one of its objectives. 15 We have previously validated this database and reported a high level of data completeness on demographic (100%) and prescription details (99.98%) (ref. 16). During each clinic visit, patients must register at first attendance with their identity documents and their demographic and socioeconomic data are entered into the computer system by clinic administrative staff in the reception office. Drug prescriptions must be entered by the attending physicians into the computer system and are double checked by staffs in the dispensary; with each prescription involving at least two independent dispensers or pharmacists for correct drug dispensing. Prescriptions can only be issued via the computerized system, including private prescriptions. Any amendments to drug prescriptions by physicians after the original consultations would also be entered into the computer system. These computerized records are the sole portal of information entry by physicians at each patient visit in all primary care clinics run by the Hospital Authority. As indicated by clinical guidelines, every physician should enter the diagnosis in the forms of International Classification of Primary Care codes after each consultation. The data sources in the present studies include patient information from the New Territory East cluster of Hong Kong (one out of its seven clusters), which provides primary health-care services to around 1.3 million residents, representing 17.2% of the Hong Kong population. 17 These records are comprehensive and allow cross-referencing by physicians when patients visit a different clinic in the public sector. The New Territory East is further divided into three separate geographical regions, namely Shatin, Taipo, and North district, from the most urbanized to the least, respectively. Their median monthly household incomes in 2006 were US$ 2,510, US$ 2,338, and US$ 2,078 for these three regions, respectively, compared to the Hong Kong-wide figure of US$ 2,240 (ref. 17 ). These three regions have similar median ages (38 39 years), comparable with the median age of 39 years for Hong Kong. This study was approved by the Survey and Research Behavioural Ethics Committee, Chinese University of Hong Kong. Informed consent was not needed, as we anonymized all patients and replaced each patient s name by a unique identifier. Definition of the cohort. All adult patients 18 years who have attended a primary care clinic at least once and received a antihypertensive medication in the New Territory East region during the study period January 2004 to June 2007 were eligible, irrespective of the number of their International Classification of Primary Care coding. We assigned the number of comorbidities to each patient according to the number of concomitant cardiovascular disorders (e.g., diabetes mellitus, lipid disorders, cerebrovascular diseases), diseases which were compelling indications or contraindications of a particular class of antihypertensive drug (e.g., asthma, gout, chronic bronchitis), or medical conditions, which could potentially confound the prescription choice of antihypertensive agents (e.g., heart failure, glomerulonephritis). A complete list of these diseases as identified by their respective International Classification of Primary Care codes is shown in Supplementary Table S1 online. Blood pressure was measured by an automated calibrated blood pressure machine after patients have adequate rest for at least 10 min. The diagnosis of hypertension was made by the physician according to his clinical judgment, which usually requires at least three separate readings of BP >140/90. Exposure to drugs and assessment of persistence. The major outcome variable is the cumulative incidences of drug discontinuation within 180 days of their prescription. Drug discontinuation is defined as the absence of a refill prescription in all subsequent clinic visits without issuance of another antihypertensive drug within the time frame of 180 days since the first prescription date. This definition is similar to previous studies 6,7 except that a longer time frame of 180 days was used instead of 90 days, taking into account the variable practice of prescribing antihypertensive drugs for a period of days (median 56 days) in our database. Covariables and statistical analysis. We used the Statistical Package for Social Sciences (SPSS, Chicago, IL). Demographic variables were reported according to the drug class prescribed (thiazide diuretics, β-blockers, CCB, angiotensin- converting enzyme inhibitors, combination therapy, and others ). Combination therapy was defined as a single pill consisting of more than one active antihypertensive ingredient. Other drug classes include α-blockers, K + -sparing diuretics, loop diuretics, vasodilators, and polytherapies (defined as the at least two separate drugs with different antihypertensive ingredients). χ 2 -Tests of heterogeneity were used to analyze categorical variables. Patients were further stratified by different gender (male vs. female), age (<50 years, years, 70 years) groups, and visit types, and covariables include patients age, gender, payment status (fee waivers vs. fee payers), service types (general outpatient vs. FMSC vs. staff clinics), district of residence (Shatin vs. Taipo vs. North district vs. others), visit type (new vs. subsequent visit), calendar years of drug prescription, and the antihypertensive drug classes. Fee waivers are almost exclusively residents receiving social security allowances from the government. AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER 7 july

3 Antihypertensive Discontinuation Among Chinese To qualify for fee waiving, patients must be comprehensively assessed by a medical social worker who determines their inability to pay for medical consultation fee. Each consultation costs US$ 5.77 including investigation and prescription fees. New users were defined as those who have never been prescribed antihypertensive medications in these primary care clinics as shown in the electronic computer system. One binary logistic regression analysis was conducted among all patients with the cumulative incidences of drug discontinuation within 180 days as the outcome variable. We further stratified patients into different age (<50, 50 69, 70 years) and gender (male and female) groups and conducted separate regression analyses to detect any differences in factors associated with antihypertensive discontinuation among these patient subgroups. Selection of independent variables was hypothesis-driven. All the predictor variables were entered unconditionally into the regression equations. All P < 0.05 were regarded as statistically significant. Results Patient characteristics From a total of 93,286 eligible patients with an average age of 62.7 years (95% confidence interval years), female patients predominate (56.8%) (Table 1). There were 1,295 patients who died before the first day of the next prescription period and were excluded from the analysis. Most were prescribed combination therapy (31.4%), followed by CCB (23.2%), and β-blockers (20.6%). The majority was fee payers (73.4%), attendees of general outpatient (90.6%), and lived in more urbanized districts (70.9%). There were 56.4% new visitors, and most had uncomplicated hypertension as their only medical condition (72.8%) (Table 1). Profiles of drug discontinuers vs. adherers There were 12,301 patients (13.2%) who have discontinued their drug prescriptions within 180 days (Table 2). When compared with drug adherers, the discontinuers were younger, more were male patients, fee waivers, attendees of FMSC or staff clinics, new visitors, and had less comorbidities (all P < 0.001, see Table 2). Significantly more discontinuers than adherers were prescribed β-blockers, and less were prescribed CCB and combination therapies. Factors associated with antihypertensive discontinuation When drug discontinuation within 180 days after their first prescription was used as a binary outcome variable in multivariate regression analysis, younger age (<50 years), male gender, fee waivers, attendees of FMSC or staff clinics, new visitors, and absence of comorbidities were significantly associated with drug discontinuation (Table 3). Compared with thiazide diuretics, users of β-blockers were more likely to have their drugs discontinued, while patients on CCB and combination therapies were less likely to experience drug discontinuation (Table 3). Patients prescribed angiotensin-converting enzyme inhibitors had similar odds of discontinuation with thiazide users. Factors associated with drug discontinuation by gender and age There were 5,780 (14.4%) male and 6,593 (12.4%) female patients who discontinued their drug prescriptions within 180 days (Table 4). For male patients, younger age (<50 years), fee waivers, visits in FMSC, absence of comorbidities, and new visits were positively associated with drug discontinuation. These independent associated factors were reported in similar magnitude among female patients (Table 4). Compared with thiazide diuretics, users of β-blockers were significantly more likely and users of CCB and combination therapies less likely to have their drugs discontinued in both male and female patients. The cumulative incidences of drug discontinuation within 180 days were 21.3, 11.5, and 18.8% in the age groups <50, 50 69, and 70 years, respectively (Table 5). Fee waivers, visits in FMSC, and new visits were positively associated with drug discontinuation in all three age groups. There were two notable differences across stratified analyses in these age groups (Table 5). First, male patients were more likely to have their drugs discontinued in the age group 70 years (adjusted odds ratio (aor) = 1.12, P = 0.002), but not the younger age groups. Second, when compared with thiazide users, users of β-blockers were significantly more likely to have drug discontinuation only in patients aged <50 years (aor = 2.43, P < 0.001) and years (aor = 1.63, P < 0.001) but not among patients aged >70 years (aor = 1.13, P = 0.091). All the covariates were tested for multicollineraity (r > 0.8 between any two variables) to ensure robustness of the regression analysis and there were no significant correlations among all variables. Discussions Major findings From 93,286 Chinese patients prescribed an antihypertensive medication, the cumulative incidence of drug discontinuation within 180 days was 13.2% overall and 17.7% for patients prescribed their first-ever antihypertensive drugs. Young age, male gender, fee waivers, visits in FMSC, new visits, and the absence of comorbidities were independently associated with drug discontinuation. Male patients were more likely to have drugs discontinued among the older age groups ( 70 years) only. Users of β-blockers were significantly associated with drug discontinuation in both genders and among the younger patients (<70 years) only, while patients prescribed CCBs and combination therapies were consistently less likely to have their drugs discontinued. Interpretations and relationship to published literatures Our findings revealed a high discontinuation rate of antihypertensive drugs 180 days after their prescription, especially among drug-naive hypertensive patients (17.7%). This is very similar to a population-based cohort study using the UK General Practice Research Database by Burke et al. 6 who reported an antihypertensive drug discontinuation rate of 20.3% at 6 months after prescription among the drug-naive. 804 july 2009 VOLUME 22 NUMBER 7 AMERICAN JOURNAL OF HYPERTENSION

4 Antihypertensive Discontinuation Among Chinese articles Table 1 Patient characteristics (N = 93,286) Age (years) Thiazide (n = 9,398) β-blockers (n = 19,177) CCB (n = 21,636) ACEI (n = 7,153) Combination a (n = 29,253) Others (n = 6,669) No. % No. % No. % No. % No. % No. % <50 1, , , , , < , , , , , , , , , , , , , , , , , , Gender Male 3, , , , , , <0.001 Female 6, , , , , , Fee waivers 2, , , , , , <0.001 Fee payers 6, , , , , , GOPC 8, , , , , , <0.001 FMSC , , , , Staff clinics Shatin 4, , , , , , <0.001 Taipo 1, , , , , , North 2, , , , , , Others , , , New 5, , , , , , <0.001 Subsequent 3, , , , , , Comorbidities 0 7, , , , , , < , , , , , , , Calendar years of prescription , , , , , , < , , , , , , , , , , , , , , , All the percentages are across columns. The P values represent χ 2 -tests of heterogeneity comparing the respective proportions among the first four drug classes across rows. Others include α-blockers, K + -sparing diuretics, loop diuretics, vasodilators, and polytherapy. ACEI, angiotensin-converting enzyme inhibitors; CCB, calcium channel blockers; FMSC, family medicine specialist clinic; GOPC, general outpatient clinics. a Combination therapies refer to the prescription of a single pill consisting of 2 active antihypertensive ingredients. P A database study in Canada by Caro et al. 18 found that 16% of patients discontinued their antihypertensive medications within 6 months of drug issuance. There were also similar observational studies which reported high incidences of drug discontinuation, 7 10,18 24 highlighting the need for primary care physicians to monitor patients closely particularly for those prescribed their first-ever antihypertensive medication. Young age has also been reported by a few studies 6,18,19 as a relevant predictor of drug discontinuation. The other independent associated factors found in this study, namely patients with lower socioeconomic status (fee waivers), new clinic attendees, and visits in a family medicine specialist setting, have not been reported in published literatures thus far. The exact reasons remained to be explored. Our findings that patients with concomitant morbidities had lower likelihood of drug discontinuation were compatible with Caucasian studies showing better antihypertensive adherence among patients having multiple chronic conditions. 18,25,26 AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER 7 july

5 Antihypertensive Discontinuation Among Chinese Table 2 Characteristics of discontinuers vs. adherers (N = 93,286) Age (years) Discontinuers (n = 12,301) Adherers (n = 80,985) No. % No. % <50 3, , < , , , , , , Gender Male 5, , <0.001 Female 6, , Fee waivers 3, , <0.001 Fee payers 8, , GOPC 10, , <0.001 FMSC 1, , Staff clinics Shatin 5, , <0.001 Taipo 2, , North 2, , Others 1, , New 9, , <0.001 Subsequent 3, , Comorbidities 0 10, , < , , , Calendar years of prescription , , < , , , , , , Drug class Thiazide 1, , <0.001 β-blockers 3, , CCB 2, , ACEI 1, , Combination a 2, , Others 1, , All the percentages are across columns. The P values represent χ 2 -tests of heterogeneity comparing the respective proportions across rows. Others include α-blockers, K + -sparing diuretics, loop diuretics, vasodilators, and polytherapy. ACEI, angiotensin-converting enzyme inhibitors; CCB, calcium channel blockers; FMSC, family medicine specialist clinic; GOPC, general outpatient clinics. a Combination therapies refer to the prescription of a single pill consisting of 2 active antihypertensive ingredients. P It has been suggested that the Health Belief Model fits in the explanation, where patients perceiving themselves to be sicker tend to comply better to physicians management. 25 Regarding the comparison among the major antihypertensive drug classes, the majority of studies showed a consistent rank order of antihypertensive class-specific discontinuation; angiotensin receptor blocker and angiotensin-converting enzyme inhibitors were associated with the highest adherence rate, followed by CCB or β-blockers, and thiazides. 7,9,10,19 21,23,24 In addition, fixed-dose combination therapies have recognized advantages of better patient adherence because they can usually be administered once daily. 27,28 These studies were, however, conducted among Caucasian populations. A recent local study involving 2,531 consecutive patients in two outpatient clinics in Hong Kong 29 reported lower short-term discontinuation rates of thiazides and higher long-term discontinuation rates of CCB, but it is small-scaled and less likely to be representative. Our study pointed toward the lower adherence rate of β-blockers in younger male and female patients, and the higher adherence rates of CCBs and combination therapies in all patients which could be a new finding among patients of Chinese ethnicity. This may be due to implementation of authoritative guidelines including the British Hypertension Society 30 and the National Institute of Clinical Excellence, 31 which do not recommend β-blockers as a preferred initial antihypertensive therapy. On the other hand, there have been reports on the wide spectrum of β-blocker related side effects like depression, fatigue, and sexual dysfunction 32 and its higher discontinuation incidences may be due to drug intolerability. 33 Also we showed an important observation that elderly male patients of Chinese race were more likely to have drug discontinuation, which could well be attributed to ethnic differences in the pharmacological effects of different antihypertensive agents. 12 Strengths and limitations As far as we are aware, our study is the largest evaluation ever conducted in the Asia Pacific region on the discontinuation profiles of antihypertensive drugs in patients treated in primary care. The major strength of our study is therefore the robust sample size generated over a 3.5-year period. Besides, we captured data in clinical practices not under research settings, allowing the findings to be more reflective of reallife practice. The strengths and weaknesses of the electronic database from which this study was drawn have been discussed previously. 19 The use of dispensing data instead of drug administration may lead to nondifferential information bias, and cannot take into account lifestyle changes after prescriptions. Nevertheless, administrative databases have many advantages to measure drug exposure when compared to other data collection methods like interviews or self-administered surveys as the latter could induce recall biases. 34 In this study, we also included patients with concomitant cardiovascular diseases and coded conditions that might influence the choice of antihypertensive agent prescribed, allowing analysis in a wider spectrum of hypertensive patients with different comorbidity profiles. 806 july 2009 VOLUME 22 NUMBER 7 AMERICAN JOURNAL OF HYPERTENSION

6 Antihypertensive Discontinuation Among Chinese articles Table 3 Factors associated with antihypertensive discontinuation 180 days after the first date of prescription (N = 93,286, r 2 = 0.21) Age (years) n % Discontinuation Crude OR Adjusted OR P <50 3, (ref.) 1.00 (ref.) , ( ) 0.63 ( ) < , ( ) 0.52 ( ) < , ( ) 0.70 ( ) <0.001 Gender Female 6, (ref.) 1.00 (ref.) Male 5, ( ) 1.05 ( ) Fee waivers 3, (ref.) 1.00 (ref.) Fee payers 8, ( ) 0.83 ( ) <0.001 GOPC 10, (ref.) 1.00 (ref.) FMSC 1, ( ) 1.70 ( ) <0.001 Staff clinics ( ) 1.64 ( ) <0.001 Shatin 5, (ref.) 1.00 (ref.) Taipo 2, ( ) 0.96 ( ) North 2, ( ) 0.94 ( ) Others 1, ( ) 1.54 ( ) <0.001 New 9, (ref.) 1.00 (ref.) Subsequent 3, ( ) 0.54 ( ) <0.001 Comorbidities 0 10, (ref.) 1.00 (ref.) 1 1, ( ) 0.66 ( ) < ( ) 0.60 ( ) <0.001 Drug classes Thiazide 1, (ref.) 1.00 (ref.) β-blockers 3, ( ) 1.67 ( ) <0.001 CCB 2, ( ) 0.76 ( ) <0.001 ACEI 1, ( ) 1.06 ( ) Combination a 2, ( ) 0.73 ( ) <0.001 Others 1, ( ) 3.22 ( ) <0.001 All the percentages represent the proportion of patients discontinued their medications 180 days within the first date of drug prescription and are across rows. Others include α-blockers, K + -sparing diuretics, loop diuretics, vasodilators, and polytherapy. ACEI, angiotensin-converting enzyme inhibitors; CCB, calcium channel blockers; FMSC, family medicine specialist clinic; GOPC, general outpatient clinics; OR, odd ratios; ref, reference. a Combination therapies refer to the prescription of a single pill consisting of 2 active antihypertensive ingredients. Our sample is from the Hospital Authority responsible for only one territory of Hong Kong. However, similar patterns of prescribing to those found in this study have been reported in previous smaller studies in other clusters of Hong Kong and thus it is likely that our findings are generalizable in terms of primary care within the public health-care system in Hong Kong. We cannot of course extrapolate our findings to the private health-care sector. Nevertheless, uncomplicated hypertension is the second most common condition seen in primary care clinics in the public health-care sector in Hong Kong, 38 and available data suggest that the vast majority of the population attends the public health services rather than the private sector for management of hypertension. 39 Thus our findings may well be of significance at population level in terms of hypertension management and health-care costs. AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER 7 july

7 Antihypertensive Discontinuation Among Chinese Table 4 Factors associated with antihypertensive discontinuation 180 days after the first date of prescription in male and female patients (N = 93,286) Age (years) Male patients (n = 40,256; r 2 = 0.20) Female patients (n = 53,030, r 2 = 0.21) n % Crude OR Adjusted OR P n % Crude OR Adjusted OR P <50 1, (ref.) 1.00 (ref.) 1, (ref.) 1.00 (ref.) , ( ) 0.64 ( ) < , ( ) 0.63 ( ) < , ( ) 0.54 ( ) < ( ) 0.50 ( ) < , ( ) 0.73 ( ) < , ( ) 0.67 ( ) <0.001 Fee waivers 1, (ref.) 1.00 (ref.) 1, (ref.) 1.00 (ref.) Fee payers 3, ( ) 0.82 ( ) < , ( ) 0.83 ( ) <0.001 GOPC 5, (ref.) 1.00 (ref.) 5, (ref.) 1.00 (ref.) FMSC ( ) 1.55 ( ) < ( ) 1.83 ( ) <0.001 Staff clinics ( ) 1.35 ( ) ( ) 1.85 ( ) <0.001 Shatin 2, (ref.) 1.00 (ref.) 3, (ref.) 1.00 (ref.) Taipo 1, ( ) 0.92 ( ) , ( ) 0.99 ( ) North 1, ( ) 0.95 ( ) , ( ) 0.93 ( ) Others ( ) 1.40 ( ) < ( ) 1.70 ( ) <0.001 New 4, (ref.) 1.00 (ref.) 4, (ref.) 1.00 (ref.) Subsequent 1, ( ) 0.57 ( ) < , ( ) 0.53 ( ) <0.001 Comorbidities 0 4, (ref.) 1.00 (ref.) 5, (ref.) 1.00 (ref.) 1 1, ( ) 0.61 ( ) < ( ) 0.70 ( ) < ( ) 0.54 ( ) < ( ) 0.68 ( ) Drug classes Thiazide (ref.) 1.00 (ref.) (ref.) 1.00 (ref.) β-blockers 1, ( ) 1.34 ( ) < , ( ) 1.89 ( ) <0.001 CCB ( ) 0.69 ( ) < , ( ) 0.80 ( ) <0.001 ACEI ( ) 1.05 ( ) ( ) 1.02 ( ) Combination a 1, ( ) 0.70 ( ) < , ( ) 0.72 ( ) <0.001 Others 1, ( ) 3.07 ( ) < ( ) 3.27 ( ) <0.001 All the percentages represent the proportion of patients discontinued their medications 180 days within the first date of drug prescription and are across rows. Others include α-blockers, K + -sparing diuretics, loop diuretics, vasodilators, and polytherapy. ACEI, angiotensin-converting enzyme inhibitors; CCB, calcium channel blockers; FMSC, family medicine specialist clinic; GOPC, general outpatient clinics; OR, odd ratios; ref, reference. a Combination therapies refer to the prescription of a single pill consisting of at least two active antihypertensive ingredients. The regression models were far from complete as reflected by the goodness of fit (r 2 = ), and there were covariables, which could not be taken into account in database studies. In addition, we did not take into account the mean dose of drug prescription into the regression analyses, although our previous evaluations have shown that >90% of the prescriptions were of medium strengths in terms of standard equivalent dosages and there were no statistical differences across drug classes. 40 Also, it was recognized that the use of an inception cohort is a better design simulating the situation of a randomized controlled trial, where this study analyzed both new and follow-up patients. In summary, this study has evaluated the factors associated with antihypertensive discontinuation among ethnic Chinese and its cumulative incidences were high 180 days after their prescriptions. Major stakeholders of the primary care team including physicians and pharmacists should practice meticulous monitoring and counseling of patient adherence to medication after prescriptions, particularly among younger patients on β-blockers, the socioeconomically underprivileged, drug-naive patients, and male patients in the older age groups. From a health-system point of view, it raises the need to implement more innovative and realistic 808 july 2009 VOLUME 22 NUMBER 7 AMERICAN JOURNAL OF HYPERTENSION

8 Antihypertensive Discontinuation Among Chinese articles Table 5 Factors associated with antihypertensive discontinuation within 180 days in patients of different age groups Gender <50 years (n = 14,591, r 2 = 0.22) n % Crude OR years (n = 43,969, r 2 = 0.19) Adjusted OR P n % Crude OR 70 years (n = 21,988, r 2 = 0.19) Adjusted OR P n % Crude OR Adjusted OR Female 1, (ref.) 1.0 (ref.) 2, (ref.) 1.0 (ref.) 2, (ref.) 1.0 (ref.) Male 1, ( ) ( ) , ( ) ( ) , ( ) ( ) Fee waivers 1, (ref.) 1.0 (ref.) 1, (ref.) 1.0 (ref.) 1, (ref.) 1.0 (ref.) Fee payers 2, < , ( ) ( ) ( ) 0.85 ( ) < , ( ) 0.88 ( ) GOPC 2, (ref.) 1.0 (ref.) 4, (ref.) 1.0 (ref.) 3, (ref.) 1.0 (ref.) FMSC < ( ) ( ) ( ) Staff clinics ( ) ( ) 1.90 ( ) ( ) ( ) < ( ) P <0.001 ( ) ( ) ( ) Shatin 1, (ref.) 1.0 (ref.) 2, (ref.) 1.0 (ref.) 1, (ref.) 1.0 (ref.) Taipo ( ) ( ) North ( ) ( ) , ( ) ( ) ( ) ( ) Others < ( ) ( ) ( ) 1.52 ( ) ( ) ( ) ( ) ( ) < ( ) <0.001 ( ) New 2, (ref.) 1.0 (ref.) 3, (ref.) 1.0 (ref.) 3, (ref.) 1.0 (ref.) Subsequent < , ( ) ( ) ( ) Comorbidity 0.54 ( ) < , ( ) 0.54 <0.001 ( ) 0 2, (ref.) 1.0 (ref.) 4, (ref.) 1.0 (ref.) 2, (ref.) 1.0 (ref.) < ( ) ( ) ( ) > ( ) ( ) Drug classes 0.60 ( ) ( ) ( ) < ( ) < ( ) 0.72 <0.001 ( ) 0.61 <0.001 ( ) Thiazide (ref.) 1.0 (ref.) (ref.) 1.0 (ref.) (ref.) 1.0 (ref.) β-blocker 1, < , ( ) ( ) ( ) CCB ( ) ( ) ACEI ( ) ( ) Combination a ( ) ( ) 1.63 ( ) ( ) ( ) ( ) ( ) ( ) ( ) Others < ( ) ( ) ( ) 3.47 ( ) < ( ) < ( ) 1.13 ( ) <0.001 ( ) ( ) ( ) < ( ) < ( ) <0.001 ( ) 2.69 <0.001 ( ) All the percentages represent the proportion of patients discontinued their medications 180 days within the first date of drug prescription and are across rows. Others include α-blockers, K + -sparing diuretics, loop diuretics, vasodilators, and polytherapy. ACEI, angiotensin-converting enzyme inhibitors; CCB, calcium channel blockers; GOPC, general outpatient clinics; FMSC, family medicine specialist clinic; OR, odd ratios; ref, reference. a Combination therapies refer to the prescription of a single pill consisting of 2 active antihypertensive ingredients. AMERICAN JOURNAL OF HYPERTENSION VOLUME 22 NUMBER 7 july

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