Antihypertensive medication prescription patterns and time trends for newly-diagnosed uncomplicated hypertension patients in Taiwan

Hypertension, a leading contributor to the global burden of causes of disease, continues its upward growth trend [1‐4]. Poor control of this highly prevalent disease can lead to the development of ischemic heart disease, heart failure, stroke and chronic renal insufficiency [3‐7]. Along with its comorbidities, hypertensive related conditions have accounted for almost a third of the total causes of death in Taiwan in recent years [8]; in 2003 the total pharmaceutical expenditure on antihypertensive medication was US$0.32 billion, accounting for approximately 27% of the overall annual outpatient pharmaceutical expenditure on western-style medicines [9].

As a result of various clinical trials and studies, a range of clinical guidelines on antihypertensive treatment have been published over the past decade [10‐15]. Based on clinical evidence and cost-effectiveness [16‐18], guidelines developed by the Joint National Committee (JNC) in the United States [11] and the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom [13] recommended that diuretics (particularly thiazide-type diuretics) should be the drug of first choice for patients with no compelling indications. However, the results of various studies have shown that adherence to such clinical guidelines and recommendations are not at all uniform; indeed, they have been found to vary by time period and country, and by the characteristics of patients and physicians [19‐23].

Taiwan's National Health Insurance (NHI) has not yet established a definite guideline for antihypertensive drug therapy. Given the enormous growth in healthcare expenditure within the NHI (from US$13.9 billion in 1997 to US$20.5 billion in 2005) [24] and the limited resources for healthcare, there is a clear need to explore physician practices, including prescription trends, in antihypertensive and other therapies [25, 26].

The computerized reimbursement database of the NHI in Taiwan provides us with a valuable opportunity to assess the real practice patterns of antihypertensive pharmaceutical therapies. The NHI program, which is a mandatory nationwide health insurance system, was implemented in Taiwan in March 1995. Overall coverage continues to rise, from 96.2% in 2000 to 98.3% in 2006, and almost the entire population of Taiwan is now covered by the system [27]. Furthermore, in contrast to the NHI systems of many Western nations, patients in Taiwan are free to choose care providers in a competitive healthcare market.

The objectives of this study are to determine antihypertensive medication prescription patterns and time trends among newly-diagnosed cases of uncomplicated hypertension in Taiwan, to attempt to identify the determinants of the choice of first-line drug therapy, and to investigate the pharmaceutical costs associated with different antihypertensive agents.

The dataset contained a total of 15,835 patients over the age of 30 years who had received their initial dose of antihypertensive drugs for essential hypertension between 1 January 1998 and 31 December 2004. Of this total, 9,299 were excluded on the basis that one or more earlier comorbidities had been recorded. We were therefore left with a total of 6,536 patients and 178,754 prescriptions for antihypertensive agents for subsequent analysis.

Of the total sample of 6,536 patients, 3,268 (50.0%) were women and 49.3% were ≥55 years old, with a mean of 55.9 and SD of 12.3 years. The mean follow-up duration after the first prescription of antihypertensive medication was 42.8 ± 27.2 months, while the average number of overall prescriptions was 27.3 ± 26.0. Each prescription included 1.64 ± 0.84 antihypertensive drugs prescribed for an average period of 22.3 ± 10.5 days. The mean number of actual medical visits over the entire period of study was 25.1 ± 24.5.

This is one of the first studies of its kind to undertake an assessment of the national prescription patterns and time trends in Taiwan for antihypertensive medication for uncomplicated hypertension. We found that whether in mono-therapies or overall treatment, CCBs were the most commonly prescribed drugs, followed by beta-blockers. Amongst all of the mono-therapies, the lowest average daily medication costs were for diuretics, at less than one third of the costs for CCBs or ACE inhibitors, and about one fifth of the costs for ARBs. The prescription rate for diuretics was, however, surprisingly low, accounting for only 8.3% of all mono-therapies, and indeed the diuretic prescription rate was the second lowest of all, only after ARBs (5.7%).

Beginning in 2006–7, the National Health Research Institutes of Taiwan has begun to draft clinical guidelines for various health conditions, including the treatment of hypertension. However, most physicians seemed to accept the recommendation of the US JNC or the WHO/ISH guideline during the time of this study. The evidence-based clinical guidelines for antihypertensive treatment published by both the JNC in 2003 [11] and the NICE in 2004 [13] contained recommendations for low dosages of thiazide diuretics as the first-line drug for essential hypertension with no compelling indications. Such a recommendation also appeared in the 2003 statement published by the WHO/ISH [28]; and indeed, diuretics have been found to be the mainly prescribed class of antihypertensive drugs in the United Kingdom, Denmark and the United States [20, 29, 30].

Researchers have indicated a substantial potential for cost savings if thiazides are prescribed rather than other more expensive drugs for treatment of hypertension [31, 32]. Given that the prescription pattern in Taiwan appears to utilize more non-thiazide medications that are generally more expensive, this issue would be worthy of further study with the aim of comparing the cost-effectiveness of antihypertensive treatment in Taiwan with those of other countries.

Considerable variation in antihypertensive prescribing patterns exists internationally. Fretheim and colleagues compared the sale figures of antihypertensive drugs for six countries, reporting that thiazide diuretics accounted for 25% of consumption in the UK, while the corresponding figure for Norway was only 6% [30]. According to our assessment, thiazide diuretics accounted for 7.2% of overall antihypertensive drugs prescribed for uncomplicated hypertension in Taiwan. The relatively low prescription rate of thiazides for antihypertensive treatment appears similar to those of Norway and France, and is very different from that of the UK or Denmark.

In the absence of any guideline or effective regulations on prescribing behavior for clinicians, the current prescription pattern in Taiwan is probably a reflection of the mixed effect of the preferences of physicians, the hypotensive efficacies of medications, and the tolerance levels of patients. Under a healthcare system of mixed conventional medicine and traditional Chinese medicine, Taiwanese patients appear to dislike diuretics for the treatment of hypertension possibly because of the label 'diuresis', a term generally regarded as treating 'edema' and affecting one's kidney function in traditional Chinese medicine. The mono-therapy prescription rate for diuretics, at less than 10%, albeit with a slightly increasing trend with the passage of time (as shown in Figures 2 and 3), also implies that diuretics are currently considered in Taiwan to be only a second- or third-line medication; thus, there would appear to be considerable room for improvement, in terms of greater adherence to the existent clinical guidelines based on evidence as well as cost-effectiveness [16, 18].

The trend toward increasing numbers of prescriptions involving ARBs, as summarized in Table 4, is also worthy of some attention. Indeed, the multiple logistic regression analysis indicated that the calendar year and the size of the clinical facility were actually the major determinants, although we deliberately restricted our subjects to those newly-diagnosed with uncomplicated hypertension and mono-therapies to prevent systematic differences in patients' characteristics. We have also found that primary care clinics prescribed diuretics more frequently than the larger medical facilities. We suspect that differences in cost consciousness may be an important contributor to this particular phenomenon, since the current reimbursement policy within the NHI program seems less restrictive on medical centers and regional hospitals, as compared with primary local clinics. Another possibility is that physicians in large medical facility are more frequently exposed to new drugs and tending to readily accept the latest, or most up-to-date, medications [33]. In fact, the number of ARBs on the market increased from 2 to 9 during the period of 1998–2004. Some studies suggest that promotional activities of pharmaceutical industry have a major impact on physicians' prescribing patterns [34, 35]. More evidence needs to be collected to corroborate these beliefs.

One of the limitations of this study is the potential confounding by severity of disease for different levels of clinical facilities. Because the NHI reimbursement database has no link to details on patients' blood pressure levels or laboratory data, we were unable to directly compare the severity of hypertension among various groups of patients. Nonetheless, we have limited our study subjects to newly diagnosed cases of uncomplicated hypertension with mono-therapies, and for them there is no restriction on selection of doctors under the NHI in Taiwan. In such a way, hypertensive patients initially treated at different clinical facilities might not be so much different in severity. Moreover, Table 4 indicated that medical centers used more ARBs and less ACE inhibitors after adjustment for other determinants. As the efficacy of these two types of antihypertensive medication is similar [15], it seems that ARBs might be prescribed to substitute for some ACE inhibitors in medical centers or regional hospitals and this trend probably was unrelated to the different severity of hypertension.

The NHI database provides a 200,000-person sample representing almost 1% of the overall population of 22.9 million people in Taiwan; thus, we estimate that there may have been up to 0.75 million newly-diagnosed cases of uncomplicated hypertension in Taiwan during the seven-year period of this study. If the daily drug costs for uncomplicated hypertension could be reduced by an average of US$0.3–0.6, this would result in annual savings of up to US$82–163 million in overall pharmaceutical expenditure within Taiwan's NHI. If such action were extended to incorporate all prevalent cases of hypertension throughout Taiwan, the total amount of annual savings on costs for antihypertensive drugs could even run to US$0.2 billion. Under the current limited resources, this could clearly make the NHI much more sustainable [26].

The initial prescription patterns for antihypertensive therapies for uncomplicated hypertension in Taiwan seem to be inconsistent with the current international clinical guidelines. Although diuretics are the least expensive class of antihypertensive drugs, they are nevertheless being used as a second- or third-line method of medication, with a notably low prescription rate. There has been a growing trend in the prescribing of ARBs as the initial choice of therapy for uncomplicated hypertension, particularly in medical centers and regional hospitals. These results indicate a need for greater awareness of the evidence-based guidelines for antihypertensive drug therapy amongst physicians and the general public.

Given the existence of the national health insurance system in Taiwan, there is still significant room for improvement in the cost-effectiveness of antihypertensive treatment [16, 25]. We recommend reaching a consensus on this matter and developing a domestic clinical guideline taking cost-effectiveness into consideration as soon as possible.