Clement S.K. Cheung

Drug adherence and the incidence of coronary heart disease- and stroke-specific mortality among 218,047 patients newly prescribed an antihypertensive medication: A five-year cohort study

Abstract Background Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings. Methods From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC]<40%), intermediate (40–79%), and high (≥80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models. Results From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%–79% (HR=0.46, 95% C.I. 0.41–0.52, p<0.001) and ≥80% (HR=0.91, 95% C.I. 0.85–0.98, p=0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group. Conclusions Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings.

Medication adherence to first-line antihypertensive drug class in a large Chinese population

Abstract Purpose Suboptimal adherence to antihypertensive agents leads to adverse clinical outcomes. This study aims to evaluate the association between first-line antihypertensive drug class and medication adherence in a large Chinese population. Methods All patients prescribed ≥ one antihypertensive drug in 2001–2003 and 2005 who have paid at least two consecutive clinic visits in the public healthcare system of Hong Kong were included. We excluded patients who have followed-up in the clinics for ≤30days. Interval-based Proportion of Days Covered (PDC) was used to assess medication adherence. All patients were followed-up for up to 5years. Binary logistic regression analysis was used to evaluate the factors associated with optimal adherence, defined as PDC ≥80%. Results From 147,914 eligible patients, 69.2% were adherent to the antihypertensive prescriptions. When compared with angiotensin converting enzyme inhibitors (ACEIs), patients initially prescribed α-blockers (adjusted odds ratio [AOR]=0.234, 95% C.I. 0.215–0.256), β-blockers (AOR=0.447, 95% C.I. 0.420, 0.477), thiazide diuretics (AOR=0.431 95% C.I. 0.399, 0.466) and calcium channel blockers (AOR=0.451, 95% C.I. 0.423, 0.481) were significantly less likely to be drug adherers. Angiotensin receptor blockers (ARBs) and fixed-dose combination therapies were similarly likely to be medication adherent. Older age, male gender, visits in general out-patient clinics, residence in urbanized regions, and the presence of comorbidity were positively associated with optimal drug adherence. Conclusion Patients receiving initial prescriptions of ACEIs, ARB and combination therapy had more favorable adherence profiles than the other major antihypertensive classes in real-life clinical practice.

Factors Associated With Adoption of the Electronic Health Record System Among Primary Care Physicians

Background A territory-wide Internet-based electronic patient record allows better patient care in different sectors. The engagement of private physicians is one of the major facilitators for implementation, but there is limited information about the current adoption level of electronic medical record (eMR) among private primary care physicians. Objective This survey measured the adoption level, enabling factors, and hindering factors of eMR, among private physicians in Hong Kong. It also evaluated the key functions and the popularity of electronic systems and vendors used by these private practitioners. Methods A central registry consisting of 4324 private practitioners was set up. Invitations for self-administered surveys and the completed questionnaires were sent and returned via fax, email, postal mail, and on-site clinic visits. Current users and non-users of eMR system were compared according to their demographic and practice characteristics. Student’s t tests and chi-square tests were used for continuous and categorical variables, respectively. Results A total of 524 completed surveys (response rate 524/4405 11.90%) were collected. The proportion of using eMR in private clinics was 79.6% (417/524). When compared with non-users, the eMR users were younger (users: 48.4 years SD 10.6 years vs non-users: 61.7 years SD 10.2 years, P<.001); more were female physicians (users: 80/417, 19.2% vs non-users: 14/107, 13.1%, P=.013); possessed less clinical experience (with more than20 years of practice: users: 261/417, 62.6% vs non-user: 93/107, 86.9%, P<.001); fewer worked under a Health Maintenance Organization (users: 347/417, 83.2% vs non-users: 97/107, 90.7%, P<.001) and more worked with practice partners (users: 126/417, 30.2% vs non-users: 4/107, 3.7%, P<.001). Efficiency (379/417, 90.9%) and reduction of medical errors (229/417, 54.9%) were the major enabling factors, while patient-unfriendliness (58/107, 54.2%) and limited consultation time (54/107, 50.5%) were the most commonly reported hindering factors. The key functions of computer software among eMR users consisted of electronic patient registration system (376/417, 90.2%), drug dispensing system (328/417, 78.7%) and electronic drug labels (296/417, 71.0%). SoftLink Clinic Solution was the most popular vendor (160/417, 38.4%). Conclusions These findings identified several physician groups who should be targeted for more assistance on eMR installation and its adoption. Future studies should address the barriers of using Internet-based eMR to enhance its adoption.

Factors associated with multimorbidity and its link with poor blood pressure control among 223,286 hypertensive patients

Multimorbidity has become the norm worldwide as populations age. It remains, however, infrequently researched. This study evaluated factors associated with multimorbidity in a predominantly Chinese hypertensive population. We included all adult patients prescribed their first antihypertensive agents in the entire public sector in Hong Kong from a validated database. Multimorbidity was defined as having one or more medical conditions (cardiovascular diseases; respiratory diseases; diabetes or impaired fasting glucose; renal disease) in addition to hypertension. We studied the prevalence of multimorbidity and performed multinomial regression analyses to evaluate factors independently associated with multimorbidity. 223,286 hypertensive patients (average age of 59.9 years, SD 17.6) were included. The prevalence of having 0, 1 and ≥ 2 additional conditions was 59.6%, 32.8% and 7.5%, respectively. The most common conditions were cardiovascular disease (24.2%) and diabetes (23.0%), followed by respiratory disorders (14.6%) and renal disease (10.9%). Older age (>50 years), male sex, lower household income, receipt of social security allowance and suboptimal blood pressure control (>140 mmHg or >90 mmHg; >130 mmHg or >80 mmHg for diabetes patients; AOR = 3.38-4.49) were significantly associated with multimorbidity. There exists a synergistic effect among these variables as older (≥ 70 years), male patients receiving security allowance had substantially higher prevalence of multimorbidity (19.9% vs 7.5% among all patients). Multimorbidity is very common in hypertensive patients and its prevalence increased markedly with the presence of risk factors identified in this study. Hypertensive patients with multimorbidities should receive more meticulous clinical care as their blood pressure control tends to be poorer.

Antihypertensive Prescriptions Over a 10-Year Period in a Large Chinese Population

BACKGROUND International guidelines recommending antihypertensive prescriptions for the management of hypertension have been published in the past decade. Beta-blocker use was discouraged by a significant body of evidence and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) were found more effective among younger patients. This study aims to evaluate the trends in prescription profiles in a large Chinese population because patterns of antihypertensive agent dispensation represent important information for physicians and policymakers. METHODS From clinical databases consisting of all patient records in the public health-care system of Hong Kong, we examined all antihypertensive prescriptions according to the drug classes (thiazide diuretics, alpha-blockers, beta-blockers, calcium channel blockers (CCBs), ACEIs, ARBs, fixed-dose combinations, and polytherapy (2, ≥3)) between 2001 and 2010. We retrieved >6.3 million prescription episodes for 223,287 patients. RESULTS The average age of the patients was 59.9 years (SD = 17.6), and 54.8% were women. According to prescription episodes, the most commonly prescribed medications were beta-blockers (31.7%) and CCBs (29.2%), followed by ACEIs (13.9%), thiazide diuretics (5.0%), and alpha-blockers (4.5%). Between 2001 and 2010, the prescription proportions of beta-blockers decreased from 41.5% to 21.5%, whereas that of ARBs increased from 0.5% to 1.0% (P < 0.001, χ(2) test for trend). It was found that the decline of beta-blockers (71.0% to 35.4%) and increase in ARB prescriptions (0.4% to 1.0%) were particularly marked among younger subjects aged <55 years. CONCLUSIONS These findings provided information on the prescription patterns of antihypertensive agents in a large Chinese population. It sets a future research direction to study the various reasons influencing these drug class-specific trends.

Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database

OBJECTIVE Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.

Initial Antihypertensive Prescription and Switching: A 5 Year Cohort Study from 250,851 Patients

Purpose Adverse effects of antihypertensive therapy incur substantial cost. We evaluated whether any major classes of antihypertensive drugs were significantly associated with switching as a proxy measure of medication side effects in a large Chinese population in Hong Kong. Methods From a clinical database, all adult patients newly prescribed an antihypertensive mono-therapy in Hong Kong between the years 2001–2003 and 2005 were included. Those who paid only one visit, died or stayed in the cohort for <180 days after the prescription, or prescribed more than one antihypertensive agent were excluded. The factors associated with switching at 180 days were evaluated by multivariate regression analyses. Age, gender, payment status, service type, district of residence, drug class, systolic and diastolic blood pressure levels were predictor variables. Results From 250,851 subjects, 159,813 patients were eligible. A total of 6,163 (3.9%) switched their medications within 180 days. Patients prescribed thiazide diuretics had the highest switching rate (5.6%), followed by ACEIs (4.5%), CCBs (4.4%) and beta-blockers (3.2%). When compared with ACEIs, patients on thiazide diuretics were significantly more likely to be switchers (adjusted odds ratio [AOR] 1.49, 95% C.I. 1.31–1.69, p<0.001), whilst patients prescribed CCBs and beta-blockers were similarly likely to have switching. Following these patients up for 5 years showed that thiazide had the most marked increase in switching rate. Conclusions The higher rates of switching among thiazide diuretics in this study might raise a probably greater incidence of their adverse effects in this Chinese population, yet other factors might also influence switching rates. Patients prescribed thiazide diuretics for longer term should be observed for their intolerability.

The incidence of cancer deaths among hypertensive patients in a large Chinese population: A cohort study

Current evidence is mixed regarding the association between antihypertensive prescriptions and cancer mortality. We evaluated this association in a large Chinese hypertensive population. We followed for five years all patients who were prescribed their first-ever antihypertensive agents between 2001 and 2005 in a public healthcare sector of Hong Kong. The association between antihypertensive drug class and cancer mortality was evaluated by Cox proportional hazard models with propensity score matching. Age, gender, socioeconomic status, service settings, district of residence, proportion of days covered reflecting medication adherence, and the number of comorbidities were adjusted. From 217,910 eligible patients, 9500 (4.4%) died from cancer within five years after their first-ever antihypertensive prescription. Most cancer deaths occurred in the digestive (38.9%) and respiratory system (30.4%); the breast (6.2%); and the lympho-hematopoietic tissues (5.3%). The proportion of patients who died from cancer was the highest in the calcium channel blocker (CCB) group (6.5%), followed by thiazide diuretics (4.4%), angiotensin converting enzyme inhibitors (4.2%) and β-blockers (2.6%). When compared with β-blockers, patients prescribed CCBs (Adjusted Hazard Ratio [AHR]=1.406, 95% C.I. 1.334-1.482, p<0.001) were more likely to die from cancer. Thiazide users were also more likely to suffer from cancer deaths (AHR=1.364, 95% C.I. 1.255-1.483, p<0.001), but became insignificant in stratified analysis. The association between cancer mortality and use of CCB, and perhaps thaizide, may alert physicians to the need for more meticulous and comprehensive care of these patients in clinical practice. We recommend prospective studies to evaluate cause-and-effect relationships of these associations.

Duration of initial antihypertensive prescription and medication adherence: A cohort study among 203,259 newly diagnosed hypertensive patients

BACKGROUND Optimal adherence with antihypertensive medications is crucial to prevent hypertension-related complications. This study evaluated whether the duration of initial antihypertensive prescription is associated with better medication adherence in a large sample of Chinese hypertensive patients. METHODS AND RESULTS From a validated clinical database which consists of all patients in the public healthcare sector in Hong Kong, all patients on their first-ever antihypertensive agent from 2001 to 2005 (N=203,259) were included and followed-up for 12 months (and up to 5 years in separate analyses). The average age was 58.7 years (SD 17.3), and the overall rate of optimal adherence (as measured by having the Proportion of Days Covered≥0.80) was 32.4%. The proportion of patients whose initial prescriptions lasted for ≤6 days; 7-14 days; 15-28 days and ≥29 days was 23.7%, 24.3%, 15.1% and 37.0%, respectively. The corresponding proportion of optimal adherence was 18.1%, 20.1%, 31.0% and 50.3%. The binary logistic regression analysis showed that after controlling for age, sex, socioeconomic status, service type, drug class, and district of residence, those whose initial prescription was 7-14 days (adjusted odds ratio [AOR]=1.17, 95% C.I. 1.12-1.22); 15-28 days (AOR=1.90, 95% C.I. 1.82-1.99) and ≥29 days (AOR=4.13, 95% C.I. 3.96-4.31) were significantly more likely to be adherent than those who were prescribed for ≤6 days (all p<0.001). These findings remained significant in separate analyses where the period of follow-up was extended to 5 years. CONCLUSIONS Shorter duration of first antihypertensive prescriptions was associated with poorer medication adherence, and this practice should be avoided if possible.

Cardiovascular mortality in hypertensive patients newly prescribed perindopril vs. lisinopril: A 5-year cohort study of 15,622 Chinese subjects

BACKGROUND Perindopril and lisinopril are two common ACE inhibitors prescribed for management of hypertension. Few studies have evaluated their comparative effectiveness to reduce mortality. This study compared the all-cause and cardiovascular related mortality among patients newly prescribed ACE inhibitors. METHODS All adult patients newly prescribed perindopril or lisinopril from 2001 to 2005 in all public clinics or hospitals in Hong Kong were retrospectively evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for less than a month were excluded. The all-cause mortality and cardiovascular-specific (i.e. coronary heart disease, heart failure and stroke) mortality were compared. Cox proportional hazard regression model was used to assess the mortality, controlling for age, sex, socioeconomic status, patient types, the presence of comorbidities, and medication adherence as measured by the proportion of days covered. An additional model using propensity scores was performed to minimize indication bias. RESULTS A total of 15,622 patients were included in this study, in which 6910 were perindopril users and 8712 lisinopril users. The all-cause mortality (22.2% vs. 20.0%, p<0.005) and cardiovascular mortality (6.5% vs. 5.6%, p<0.005) were higher among lisinopril users than perindopril users. From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01-1.16) and 1.18-fold (95% C.I. 1.02-1.35) more likely to die from any-cause and cardiovascular diseases, respectively. Age-stratified analysis showed that this significant difference was observed only among patients aged >70 years. The additional models controlled for propensity scores yielded comparable results. CONCLUSIONS The long-term all-cause and cardiovascular related mortality rates of lisinopril users was significantly different from those of perindopril users. These findings showed that intra-class variation on mortality exists among ACE inhibitors among those aged 70 years or older. Future studies should consider a longer, large-scale randomized controlled trial to compare the effectiveness between different medications in the ACEI class, especially among the elderly.