Summary

Objective: To study the prescription pattern of first-line anti-hypertensives and the reasons of such choices among family medicine trainees in Hong Kong.

Design: A cross-sectional telephone survey in December 2003 and January 2004.

Subjects: All present higher and basic trainees of the Hong Kong College of Family Physicians (HKCFP), as of December 2003.

Main outcome measures: (1) The choices of first-line anti-hypertensive agents prescribed to patients of different ages and genders disregarding other cardiovascular risk factors; (2) The effect of training status on the choices; (3) The underlying reasons of such choices; and (4) Whether evidence-based medicine is adopted in the decision-making process.

Results: After conducting 101 interviews, we found that diuretics were the most commonly prescribed first-line anti-hypertensive agent, followed by -blockers. The two most important reasons contributing to this finding were (1) drug tolerability and (2) effectiveness. Overall, 58% of the trainees perceived their prescription as evidence-based, and this proportion appeared to increase as the training progresses. The most influential source of reference for the trainees' choice was the World Health Organization's (WHO) 1999 Guidelines. The two most important barriers of evidence-based prescription among basic trainees were (1) time and (2) drug costs. Motivational issues were also significant barriers.

Conclusion: This study depicted how Hong Kong family medicine trainees prescribe first-line anti-hypertensives. Further studies are conducted to demonstrate the local pattern of drug tolerability and effectiveness, with which results of this study can be compared.

Keywords: Prescription, first-line, anti-hypertensives, family practice

摘要

目的：研究香港家庭醫學培訓生處方第一線抗高血壓藥的選擇及其原因。

設計：二零零三年十二月至二零零四年一月期間進行電話問卷調查。

對象：二零零三年十二月所有為香港家庭醫學院家庭醫學培訓生。

測量內容：本問卷假設病者剛被診斷患有高血壓、而沒有其他循環系統的高危因素。主要研究(1)培訓生對不同年齡、性別之病者處方那類第一線抗血壓藥物；(2)訓練年期對選擇的影響；(3)處方時的考慮因素；及(4)選擇過程是否有實證醫學根據。

結果：一百零一位香港家庭醫學培訓生接受了電話訪問。利尿劑為最常處方的第一線藥物，其次為-受體阻滯劑。處方時，藥物耐受性及藥物效用為最重要的考慮因素。整體而言，58%培訓生認為其處方有實證醫學根據；此比率隨著訓練的年期上升。最影響處方 選擇之醫學文獻，為世界衛生組織一九九九年對高血壓病所頒布之指引。基礎家庭醫學培訓生認為時間及藥物價格是實踐實證醫學的最大障礙。

結論：本研究描劃了香港家庭醫學培訓生處方第一線抗血壓藥之狀況。我們建議進一步研究本地高血壓患者對不同抗血壓藥之耐受性及臨床果效，以對照本研 究之結果。

主要詞彙：處方，第一線，抗血壓藥，基層醫療

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Introduction

Prescribing anti-hypertensive agents in primary care represents a crucial procedure in daily general practice. According to the new criteria (>140/90 mmHg), the prevalence of hypertension varies between 15-35% in urban adult populations of Asia.¹ Around 24% of patients attending a Government-operated General Out-Patient Clinic (GOPC) were prescribed with antihypertensive agents.²

Many guidelines and landmark studies across the globe are emerging to compare various anti-hypertensives, and to recommend the best first-line agent(s) (Table 1). A systematic review of 10 trials evaluating the efficacy of beta (b)-blockers on morbidity and mortality in the elderly (defined as >60 years) concluded the superiority of diuretics in efficacy, all cardiovascular end-points, and prevention of cerebrovascular events.³ The preference towards diuretics as a first-line drug was further substantiated by another meta-analysis⁴ of 23 studies revealing its fewer drop-out rates due to adverse effects.

There are, however, inconsistencies in the recommendations, as highlighted by a recent commentary of the Medical Truibune.⁵ For instance, The European Society of Hypertension-European Society of Cardiology (ESH/ESC) Guidelines for the Management of Arterial Hypertension recommend prescribing either a single agent at a low dose, or a two-drug combination at a low dose as the first-line agent.⁶ In other words, it encourages starting any class at physicians' discretion and the focus is towards patient's cardiovascular risk profiles. A prescription-based survey² in 1996 found that diuretics (mainly indapamide) and methyldopa were the most popular choices of anti-hypertensive agents in the GOPC when used as monotherapy. Moreover, newly published guidelines or national programmes^7-9 can also tremendously affect the prescription patterns.

Hence we are faced with (1) the lack of consensus in various recommendations; (2) variations in temporal trend of drug prescriptions; (3) and the lack of local studies in Hong Kong comparing different classes of anti-hypertensives. There have been thus far few local surveys investigating how primary care physicians prescribe anti-hypertensives.

In response to these problems, this survey studies the prescription pattern of first-line anti-hypertensives in the young (<65 years old) and elderly patients (>65 years old) among family medicine trainees in Hong Kong. We have also further explored the reasons for such prescription choices and whether these choices were evidence-based or not. If the choices were perceived as evidence-based, we would inquire into the single most influential literature affecting the choices; and if not, we would inquire into the most important barrier deterring evidence-based practice.

Method

We conducted a cross-sectional survey (see appendix) by administering 101 telephone interviews from December 2003 to January 2004.

The basic and higher Family Medicine trainees registered in the Hong Kong College of Family Physicians (HKCFP) in the year 2002-2003 were eligible participants.

"Basic trainees" were defined as those undergoing hospital- or community-based training offered by HKCFP in the study period.

"Higher trainees" were defined as those who (1) had completed four years of basic training; (2) were currently higher trainees in the college; or (3) had just completed the higher training in 2002, as certified and acknowledged by the Board of Vocational Training and Standards (BVTS) in the College's Annual Report 2002-2003.¹⁴ This definition of "higher trainees" is different from the present one as laid down by the HKCFP, which includes only group (2) mentioned above.

Each cluster representative or an equivalent coordinator (for basic trainees) and study group leaders (for higher trainees) were contacted. Their trainees' telephone numbers were obtained only when explicit and informed verbal consent of each trainee was obtained in advance.

Participant consent was further confirmed when the interview began. Interviewees' anonymity, confiden-tiality and the sole purpose of collecting data for research were explicitly emphasized in the process.

We erected a null hypothesis that there was no difference in the perception of evidence-based prescription among (a) hospital-based basic (HBB) trainees; (b) community-based basic (CBB) trainees; and (c) higher (HI) trainees. To assess the correlation between training status and the proportion of perceived evidence-based prescription, the c² test for trend was adopted.

Results

We received 142 telephone numbers with verbal consent to conduct interviews from the participants. Unable to contact 41 participants during the study period, we conducted 101 telephone interviews consisting of 76 basic trainees and 25 higher trainees (Table 2) from December 2003 to January 2004.

None of the participants refused or withdrew from the interviews after the investigator informed them of his identity, study purpose, confidentiality issues, anonymity, and the sole purpose of the interview for research.

For basic and higher trainees, diuretics remain the most frequently used first-line anti-hypertensive agent prescribed in both age groups and genders (Figure 1). b-blockers rank the second in their popularity for both age groups and genders. Very few trainees (<4) choose ACEIs as the first-line agent for patients without any cardiovascular risk factors.

Diuretics seem to be slightly more popular in the elderly age group. b-blockers, on the other hand, are more frequently chosen for the younger age group. In addition, calcium-channel blockers (CCBs) are less popular among higher trainees (not more than 8% of trainees in all cases) than basic trainees (at least 22% of trainee prescription among the 4 classes of drugs).

One higher trainee shows indifference to the class of first-line anti-hypertensives prescribed, regarding patients' preference and mutual consensus as the most important. Another higher trainee chose Candesartan Cilexetil (Blopress, an angiotensin A₂-receptor blocker) and Bisoprolol fumarate and Hydrochlorothiazide (Lodoz, a b-blocker and diuretic combination) as first-line agents in his clinic.

The effectiveness and tolerability are the two key factors in the choice of prescription for both basic and higher trainees (Table 3), as listed by approximately half (44-57%) of the trainees from both groups in the survey. Around one-fifth to one-fourth of the basic trainees considered other factors - including costs, administrative issues, compliance anticipation and common prescription practice - as crucial. Compliance was more highly taken into consideration (36%) by the higher trainees than the basic trainees.

Overall, 58% of trainees perceived their prescription as evidence-based (Figure 2). A c² test for trend revealed statistical significance (p<0.02), showing positive correlation between training status and perception of evidence-based prescription.

The WHO's 1999 Guidelines were highly referred to among the HBB trainees (Table 4). A few of the basic trainees also found textbooks and handbook references influential.

Similarly, the WHO Guidelines and Antihypertensive and Lipid-lowering treatment to prevent Heart Attack Trial (ALLHAT) studies attracted a significant proportion of CBB trainees. The former literature was popular among the HI trainees as well. More landmark studies were quoted including the Swedish Trial of Old Patients with Hypertension-2 and Second International Study of Infarct Survival.

Table 5 represents those trainees who did not perceive their prescription to be evidence-based. For both groups of basic trainees, time and cost represented two major barriers to evidence based medicine practice. Many respondents also considered motivational problems crucial, such as personal incentives for the extra efforts spent. More HBB trainees considered administrative issues, including drug availability and clinic constraints, as significant hindrances. For the HI trainees, more concerns were placed on drug costs and motivational issues. Time did not appear to be an important barrier.

Discussion

One possible limitation to this cross-sectional study is that the samples were not truly randomized, even though participants of various training status from each cluster were represented. Besides, there could be potential selection and recall biases. A prescription-based survey, therefore, could more accurately estimate the real prescription practices, as data would be obtained from the dispensary. However, as the authors would like to target on family medicine trainees in Hong Kong, a doctor-based survey is a suitable methodology.

Our finding is consistent with Lau et al's study² where diuretics were the commonest anti-hypertensives prescribed. However, that same study found methyldopa (9.5%) among the commonest option, whereas none of the respondents in our survey ever selected this medication. On the other hand, the Cardiovascular Health Study¹⁵ demonstrated under-utilization of diuretics, showing geographical differences in prescription patterns.

It is not surprising to see that diuretics are the most commonly chosen first-line agent since most of the evidence shown in Table 1 agrees with this finding. Most hypertensive patients, however, need more than one type of medication for adequate blood pressure control,^5,16,17 and "such an anti-hypertensive treatment cocktail should include a thiazide diuretic."¹⁸ A recent issue of the Hong Kong Medical Association continuing medical education bulletin¹⁹ has further discussed the need for combination therapy for the majority of patients. Indeed, both JNC VII¹³ and the WHO-International Society of Hypertension¹⁰ (WHO/ISH) recommended a low dose drug combination, so as to allow minimal side effects as compared to any one of the high dose single medications. In general, all the above literatures would have resulted in the trainees' preference towards diuretics as a first-line agent. Participants would also have considered both clinical (drug effectiveness, tolerability, patient compliance, long-term cardiovascular morbidity, etc.) and public health (mainly cost and drug availability) perspectives in their response.

Diuretics appear to enjoy greater popularity in the elderly age group, whereas b-blockers seem to be more commonly prescribed in the younger patients, for both genders and by both groups of trainees. The exact reasons are not clearly understood. One might argue that authoritative textbooks like General Practice²⁰ explicitly recommended such. On the other hand, trainees may perceive the need to regularly monitor for electrolyte disturbances (a side effect of diuretics) very inconvenient to the young working population, thereby choosing an alternative agent for prescription - b-blockers. Furthermore, trainees may avoid prescribing b-blockers to the elderly patients since they may be more susceptible to bradyarrhythmia (a side effect of b-blockers). However, one could also argue that b-blockers' possible side effects of impotence would deter their use in the more sexually active, younger patients. As a result, value judgment may play an important role in the decision process.

Among the trainees, effectiveness and tolerability are the key factors in considering the first-line agent. Anticipated patient compliance was also highly regarded. One of the determining factors of compliance is the tolerability of anti-hypertensives (and to a lesser degree their effectiveness), which becomes an overwhelming concern for primary care physicians in choosing the appropriate drug class.

From clinical trials,^21-23 discontinuation occurs in approximately 15% of the patients taking ACEIs, 15-20% of those taking diuretics, and 20-25% of those taking b-blockers after six months to one year of treatment. In addition, about 20% of the patients with a CCB prescription discontinued after four years of treatment.²⁴ Furthermore, compliance is important and consistency in continuing drug treatment decreases both mortality and morbidity associated with hypertension.^25,26 These have already been well established and discussed in past literatures.²⁷ >From a physician's point of view, more concerns may lie on clinical parameters, instead of other issues like costs and administrative considerations.

One might also argue that in the management of chronic diseases, tolerability of drugs is even more important than their effectiveness. This is because the prime concern is the long-term control of disease by good patient compliance rather than short-term control of blood pressure level (except in cases of hypertensive emergency).

To explain the correlation of the training status and perceived evidence-based prescription, one might point to practical experience and the continuous vocational training offered by HKCFP as causal factors. It is not known, however, whether the trend is due to the need for HBB trainees to run busy night shifts and hence resulting in less time dedicated to implementing evidence-based medicine, like literature search and database access. This is implicated in Table 5 as time is considered an important barrier towards the practice of evidence-based medicine among the basic trainees.

Prospectively, this depiction of our present prescription pattern can then be followed by a longitudinal study evaluating the effectiveness and tolerability of the various classes of anti-hypertensives in our local surgeries. The study result could be further compared and contrasted with the present pattern of prescribing.

Acknowledgements

We thank all participants who offered their valuable time in the telephone interviews.

Thanks to Dr Yiu Yuk Kwan, Dr Luk Wan, Dr Alvin Chan Chung Yuk, Dr Clement Tsang Kwong-Ka, Dr Christopher Lum Chor Ming and Prof Albert Lee for their expert advice on research logistics to help conduct an ethical study. The principal investigator also extends his gratitude to Dr Frank Chan Wan Kin, Dr Dennis So Yung Pak, Dr Benny Chung Chi Yan, Dr Edwin Chan Yin Hang, Dr Allen Ngai Ho Yin, Dr Stanley Lam King Hei and Dr Edmond Chan Chi Wai, who offered valuable insights on this study.

Special thanks to Dr Billy Chiu Chi Fai, Dr Dennis So, Dr Gavin Sin Ming Chuen and Dr Ho Pak Yin for their generous support in trainee networking.

Key messages

1. In the absence of concomitant cardiovascular risk factors, diuretics and b-blockers are the most popular first-line antihypertensive agents prescribed among family medicine trainees.
2. Drug tolerability and effectiveness are the most important factors affecting the prescription choices.
3. Overall 58% of trainees regard their prescription pattern as evidence based.
4. Time and drug costs are important barriers to evidence-based prescriptions.

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References

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Appendix: Sample Questionnaire (Questions 3-6 were analyzed in a separate discussion)

Sex (性別)： Years after graduation (畢業後年期)： Location of practice (執業地點)：   Training status (醫學訓練階段)： Higher trainees (高級程度訓練) Basic trainees, Community-based (社區為本基礎訓練) Basic trainees, Hospital-based (醫院為本基礎訓練)

(1)* In your own present practice, which drug would you mostly use as your first-line anti-hypertensive in a young (<65 y.o.) and an elderly (>65 y.o.) male patient newly diagnosed as having hypertension (HT)? He enjoyed good past health and had no concomitant cardiovascular risk factors. 在你現時執業的地方，當處理一位剛被診斷為高血壓的 (A)年輕(少於65歲)及 (B)年長(超過65歲)的男性病人時，你最先會選擇什麼抗血壓藥物？他以往的健康良好，亦沒有其他循環系統的高危因素。 (A) Young HT (Drug name) (B) Elderly HT (Drug name)   (2) If the above patient was female, what would be your drug of choice? 若以上病患者為女性，你處方的藥物為何？ (A) Young HT (Drug name) (B) Elderly HT (Drug name)   (3) If the male patient was now having diabetes mellitus, what would be your drug of choice? 若以上的男性高血壓患者同時患上糖尿病，你處方的藥物為何？ (A) Young HT (Drug name) (B) Elderly HT (Drug name)   (4) If the female patient was now having diabetes mellitus, what would be your drug of choice? 若以上的女性高血壓患者同時患上糖尿病，你處方的藥物為何？ (A) Young HT (Drug name) (B) Elderly HT (Drug name)   (5) If the male patient was now having hyperlipidaemia, what would be your drug of choice? 若以上的男性高血壓患者同時有高血脂的情況，你處方的藥物為何？ (A) Young HT (Drug name) (B) Elderly HT (Drug name)   (6) If the female patient was now having hyperlipidaemia, what would be your drug of choice? 若以上的女性高血壓患者同時有高血脂的情況，你處方的藥物為何？ (A) Young HT (Drug name) (B) Elderly HT (Drug name)   (7) What are the most important reasons of your choice in prescribing for patients without concomitant cardiovascular risk factors? (Up to 2 responses) 當你給沒有循環系統高危因素的病患者處方抗血壓藥物時，最重要的考慮因素為何？請選擇不多於兩個原因。 (A) Best tolerability profiles (最少藥物副作用) (B) Best effectiveness profiles (最高藥物果效) (C) Cost consideration (成本因素考慮) (D) Administrative (e.g. local guidelines; availability in clinics) (行政上的考慮，如診所的處方指引、藥物) (E) Anticipated patient compliance (e.g. single daily dosage) (預期中病者的藥物依從率，如只是每天一次的用藥) (F) Usual Prescription Habit as a convenience (方便；所以跟從日常處方習慣) (G) Others, please specify: (其他，請列明)   (8) Do you consider your prescription to be evidence-based in most of the circumstances? and if so, which guidelines or literature are you using? If not, what is the most important barrier deterring from its use? 在以上大部份的情況下，你認為處方抗血壓藥時是否根據實證醫學？如是，你採用的是什麼醫學指引或文獻？如否，你認為最大的攔阻如何？ Yes. Source of reference: No. Most important barrier:   *Notes: If clarification from the respondents was met, the interviewer would highlight the following points:   (1) There would be no compelling indications nor contraindications for whatever drugs subsequently chosen;   (2) On subsequent physical examinations, no complications were found   (3) The patient did not show any preference towards a particular medication

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