Evaluation of antihypertensive prescribing patterns in the western region of Saudi Arabia and its compliance with national guidelines Maghrabi IA

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ORIGINAL ARTICLE

Year : 2013 | Volume : 2 | Issue : 2 | Page : 118-126

Evaluation of antihypertensive prescribing patterns in the western region of Saudi Arabia and its compliance with national guidelines

Ibrahim Abdullah Maghrabi
Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif Western Region, Kingdom of Saudi Arabia

Date of Web Publication

10-Sep-2013

Correspondence Address:
Ibrahim Abdullah Maghrabi
Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif Western Region
Kingdom of Saudi Arabia

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2278-0521.117917

Abstract

Background: Cardiovascular diseases (CVD) are responsible for one-third of deaths worldwide. Hypertension is an extremely prevalent risk factor for CVD. Different guidelines were set to control the treatment practices of hypertension including the British guidelines, the US guidelines, and the Saudi guidelines. The adherence of physicians to guidelines is a key issue in the success of therapy and avoidance of serious health complications. However, there are no enough data about the trends of hypertension treatment in Saudi Arabia and its compliance to guidelines. Aim: The present study aims to explore the profile of antihypertensive agents prescribed, investigate the extent of adherence to the national guidelines as well as the detection of some common prescription errors in treating hypertension in the western region of Saudi Arabia. Methods: Data were collected through a semi-structured interview with prescribers using prescription profile questionnaire. Results: The results indicated great degree of deviations from the guidelines. Some deviations may be major and might seriously affect the patients' health, such as prescribing direct vasodilators for angina patients. Other deviations might be minor, where physicians frequently prescribed nonrecommended drugs.The study revealed that reasons behind such deviation included lack of information and awareness of Saudi guidelines, the impact of marketing and promotion activities of different companies, tendencies to prescribe cheaper drugs, and limited number of drugs available in hospitals. Conclusion: Results obtained showed different degrees of deviation due to complex underlying causes that necessitate arranging awareness campaigns, reviewing the hospital drug lists as well as setting regulations to guarantee adherence to guidelines.

Keywords: Hypertension, prescription patterns, Saudi hypertension management guidelines

How to cite this article:
Maghrabi IA. Evaluation of antihypertensive prescribing patterns in the western region of Saudi Arabia and its compliance with national guidelines. Saudi J Health Sci 2013;2:118-26

How to cite this URL:
Maghrabi IA. Evaluation of antihypertensive prescribing patterns in the western region of Saudi Arabia and its compliance with national guidelines. Saudi J Health Sci [serial online] 2013 [cited 2023 Mar 20];2:118-26. Available from: https://www.saudijhealthsci.org/text.asp?2013/2/2/118/117917

Introduction

Hypertension affects more than 20% of the adult Saudi population with expected increasing prevalence. It is one of the most important modifiable risk factor for cardiovascular diseases. ^[1] The management of hypertension is a key challenge in modern health systems. ^[2] The failure to control hypertension takes an unacceptable toll on patients and their families. In addition to the personal cost, to the individual patient, it creates huge, avoidable economic burdens when viewed in terms of the general population. ^[3] Nonpharmacological therapy through lifestyle changes is an important component of treatment of many cases of hypertension. ^[4] Alternatively, effective antihypertensive pharmacotherapy markedly reduces the risk of strokes, cardiac failure, and renal insufficiency due to hypertension. However, reduction in risk of myocardial infarction may be less impressive. ^[5] In clinical trials, antihypertensive therapy has been associated with reductions in stroke incidence by 35% to 40%, myocardial infarction by 20% to 25% and heart failure by more than 50%. ^[6]

Despite the overwhelming evidences that lowering blood pressure reduces morbidity and mortality, its management remains frequently suboptimal due to a sinister combination of poor patient compliance and health care provider's indifference. ^[1] Moreover, different interfering factors such as price considerations ^[7] and promotion activities ^[8] were reported to have a profound impact on the prescription pattern. To overcome such discrepancies, different guidelines were set to control the treatment practices in hypertension. The most prominent were the British guidelines produced by British Hypertension Society (BHS), ^[9] the US guidelines by the 7 ^th Joint National Committee on prevention and detection of hypertension (JNC7), ^[10] the WHO/ISH guidelines, ^[11] and the European guidelines for the Management of Hypertension. ^[12] On the national level, the Ministry of Health in Saudi Arabia in collaboration with the National Commission for hypertension has developed Saudi Hypertension Management Guidelines since 2006 (SHMG). ^[1] Despite of presence of such guidelines, the adherence of physicians in Kingdom of Saudi Arabia (KSA) to them remains a question. Accordingly, the present study aims to explore the prescription profile of antihypertensive agents in the western region of Saudi Arabia, analyze the extent of adherence to the guidelines together with pointing outsome common prescription errors in treating hypertension in this region.

Materials and Methods

Data source

Data were collected through a semistructured interview carried out using prescription profile questionnaire with a total of 277 prescriber distributed in 11 hospitals of different types located in the western region of Saudi Arabia (Makkah, Jeddah, and Taif cities). The questionnaire was concerned with their prescribing decisions for antihypertensive agents in patients with different health conditions, including mild hypertension, severe hypertension, and hypertension in young and elderly patients in addition to hypertension associated with different comorbidities. The interview was also concerned with elucidating reasons for their therapeutic decisions. The questionnaire was circulated to internists, cardiologists, gynecologists, and family doctors.

Inclusion criteria

For physicians

The specialties included are internists, cardiologists, and family medicine
Physicians should be of at least 1 year of experience in KSA.

For hospitals

Should cover public and private sectors;
Should cover specialized and general sectors;
Should cover all geographical parts of western region;
Should cover all socioeconomic levels.

Outcome parameters

Percentage of application of lifestyle modification for treatment of hypertension;
Percentage of adherence to guidelines;
Percentage of prescription errors;
Impact of prescription errors on patient health.

Statistical analyses and ethics

Data were analyzed using InStat (ANOVA) software. The Chi-square test was carried out to determine the statistical significance of the differences between the prescription rates. A P value more than equal to 0.05 will be considered to be statistically significant. Ethical approval was not necessary because all data will be anonymized.

Results and Discussion

Characteristics of the interviewed physicians

A total of 277 physicians were interviewed. The physicians were selected to represent both specialized and general hospitals [Figure 1]a, both private and governmental hospitals [Figure 1]b, as well as different specialties that commonly deal with cases of hypertension [Figure 1]c. Such distribution was selected to enable comparison in prescription trends in different types of hospitals. The higher number of interviews from governmental hospitals compared to private ones was due to the lesser recruitment by private organizations since they keep cost-effectiveness into their consideration. Eighty percent of the interviewed physicians were internists, 7% were family medicine doctors, and 13% were cardiologists [Figure 1]c. Such distribution matches with the objectives of our study since most of the hypertensive cases are reviewed by these specialties.

Figure 1: (a) Distribution of the interviewed physicians according to hospital type, (b) hospital ownership, (c) and physician specialty

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The overall and country-specific experience of the interviewed physicians as well as the number and type of hypertensive patients they see annually are summarized in [Table 1].

Table 1: Characteristics of the interviewed physicians

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Trends in treatment of mild uncomplicated hypertension

Results obtained revealed that only 10% of the physicians initially tended to recommend lifestyle modification with no drug therapy in patients with mild hypertension (diastolic blood pressure is ≤100 with no complications) (data not shown). Such observation reflects a great deviation from the Saudi, ^[1] the British, ^[9] and US guidelines. ^[10]

Moreover, only 30% of those who initiate drug therapy prescribe diuretics [Figure 2]a disagreeing with the Saudi guidelines which recommend thiazide diuretics to be used in most cases of mild uncomplicated hypertension. In contrast, a large percentage (60%) of the physicians prescribe the angiotensin-converting enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) [Figure 2]a in complete deviation from the guidelines, which only recommend such drugs for some special cases of mild hypertension. In addition to conflicting guidelines, these results are inconsistent with that reported in the systemic review of Musini et al., ^[13] about loop diuretics in cases of mild hypertension. Another conflict was observed in 10% of the prescribers who tend to use combination therapy [Figure 2]a which is completely restricted for such cases. ^[1]

Figure 2: (a) Trends in treating mild uncomplicated hypertension in all visited hospitals, (b) private hospitals, (c) and in specialized versus general hospitals

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Such deviations were observed in both governmental as well as private hospitals where ACEI drugs were the first choice earlier, while CCBs were first priority in the latter hospitals [Figure 2]b. A pattern similar to that in governmental hospitals was found in specialized hospitals with a higher striking use of combination therapy exceeding 20% [Figure 2]c.

Trends in treatment of severe uncomplicated hypertension

Results illustrated in [Figure 3]a show that about 60% of the physicians prescribe monotherapy from different antihypertensive classes in conflict with the guidelines, which recommend combination therapy including two drugs for severe hypertension.

Figure 3: (a) Trends in treating severe uncomplicated hypertension in all visited hospitals and (b) in specialized versus general hospitals

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Similar trends toward monotherapy were observed in both specialized and general hospitals. Within this trend, the ACEIs and DVDs were drugs of choice in specialized hospitals, while the CCBs and DVD were the most commonly prescribed in the general ones [Figure 3]b. The pattern in governmental hospitals was nearly similar to that of specialized ones and the pattern in private hospitals was coinciding with that of general ones (data not shown). More strikingly, it was noticeable that 50% of the prescribed combinations contained renin-angiotensin system (RAS) acting drugs together with BBs (data not shown) conflicting many guidelines discouraging such combinations. ^[14]

Trends in treatment of young uncomplicated hypertensive patients

According to SHMG, ^[1] young hypertensive patients should receive BBs as first-line therapy. However, only 24.3% of screened prescribers usually did that [Figure 4]a, while the most frequently used drugs were the ACEIs with a percentage exceeding 30%. Nearly, similar patterns were observed upon analyzing the data coming from specialized hospitals and general hospitals (data not shown). Interestingly, the use of BBs was more significantly pronounced in the private hospitals than in the governmental ones (P ≤ 0.05) reflecting lack of adherence to guidelines in the latter hospitals [Figure 4]b.

Figure 4: (a) Trends in treating young uncomplicated hypertensive patients in all visited hospitals and (b) in specialized versus general hospitals

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Trends in treatment of old uncomplicated hypertensive patients

According to SHMG, the old hypertensive patients are those exceeding 65 years. For those patients, the guidelines recommend low-dose thiazide therapy (12.5-25 mg of hydrochlorothiazide or equivalent) as the first-line hypertension treatment and long acting CCBs as second choice. Moreover, it states that BBs are less appropriate as first-line therapy for uncomplicated hypertension in the elderly. ^[1]

As demonstrated in [Figure 5], the physicians were sticking to guidelines in 38.9% of cases. However, a large proportion of them (61.1%) tended to initially prescribe other classes of antihypertensive agents as CCBs, BBs, and ACEIs. More strikingly, they showed no special considerations regarding the doses in this special population (data not shown) conflicting the guidelines recommendation for the elderly dose to be half of that used in younger patients according to the concept of "Start low and go slow". ^[1] The same deviation was also observed upon analyzing the results from governmental and private hospitals with more tendency to BBs in the former hospitals and to CCBs in the latter ones (data not shown).

Figure 5: Trends in treating old uncomplicated hypertensive patients

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Despite the fact that SHMG proposes sodium reduction in elderlydue to their greater sensitivity to sodium intake, the interviewed physicians were neither aware about that (data not shown).

Trends in treatment of pregnant hypertensive patients

According to SHMG, ^[1] methyldopa is the drug of choice for pregnant hypertensive women, while labetalol is the drug of choice for those who have concommitant renal diseases.

In this regard, a moderate degree of adherence to such guidelines (about 60%) was observed in the present study [Figure 6]. Surprizingly, there was a considerable trend toward direct vasodilators which is completely excluded from SHMG recommendations [Figure 6]. The above-mentioned patterns were nearly similar despite of the hospital type with no significant difference in most cases (P ≤ 0.05).

Figure 6: Trends in treating pregnant uncomplicated hypertensive patients

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Trends in treatment of hypertension associated with chronic renal diseases

An increased prevalence of hypertension with renal function decline has been previously reported. On the contrary, lowering blood pressure was found to be linked with reducing the progression of renal disease. Such observations imply an etiological link between both health problems. ^[15] To treat hypertension in such population, SMHG ^[1] proposes ACEIs and to a less extent loop diuretics or nondihydropyridine CCBs as drugs of choice.

In this study, about 40% of the interviewed physicians preferred CCBs as first line to treat hypertensive patients with CRD in contrast to guidelines that recommended ACEIs [Figure 7]a. In addition to conflicting with the guidelines, such inverted priorities disagree with several articles which recommend drugs that block the RAS as antihypertensive drugs of choice in patients with concomitant renal diseases. ^[15] A very limited use of diuretics (about 7%) was also observed disagreeing with the national guidelines, which claimed additional advantages for loop diuretics of correcting the hyperkalemia associated with renal diseases. ^[1] Moreover, it also contradicts with the principle of cost-effectiveness achieved by diuretics. Indeed, systematic reviews and meta-analysis of major hypertension trials have provided evidences that low-dose diuretics areas are effective at lowering blood pressure as the expensive agents such as ACEIs and ARBs. ^{[16],[17],[18],[19]} Similar observation was reported in a study of Rochefort et al., ^[20] about Quebec hospitals. Our discussion with the prescribers revealed that limited use of diuretics was owed to concerns and misconceptions about safety of diuretics in such cases (data not shown). Interestingly, such interpretation coincides with that reported by Rochefort et al.,^[20] despite of the difference in physician experience or educational background. Such misconception reflects lack of awareness about many meta-analysis studies that revealed diuretics to be equally or better tolerated than the newer antihypertensive agents. ^[16],[18]

Figure 7: (a) Trends in treating hypertension associated with chronic renal diseases in all visited hospitals, (b) in governmental versus private hospitals, (c) and in specialized versus general hospitals

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As compared with those in specialized hospitals, the prescribers in general hospitals showed more tendency toward AMD, ARBs, and combinations (P ≤ 0.05) [Figure 7]b. Moreover, [Figure 7]c shows a significantly higher adherence to guidelines in governmental hospitals as compared with private ones manifested in markedly higher use of ACEIs (P ≤ 0.05).

Trends in treatment of hypertension associated with hepatic disorder

For treatment of hypertension accompanied with hepatic disorders, the drug of choice according to many prescribers were diuretics, BBs, ACEIs, and CCBs with about 28.2%, 18.6%, 15.8%, and 17.7%, respectively [Figure 8]. The observed high tendency toward BB conflicts with the SHMG ^[1] which banned the use of most BB in case of hepatic problems. Such deviation may result in serious problems and affects the health of patients. It was also noticeable that this behavior was consistant despite of the hospital type.

Figure 8: Trends in treating hypertension associated with hepatic disorders

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Trends in treatment of hypertension associated with bronchial asthma

For treatment of hypertension in asthmatic patients, the SHMG ^[1] recommended the use of thiazide diuretics or potassium sparing diuretics as the first-line therapy while it restricted the use of BB that may aggrevate the asthma. Surprizingly, results obtained [Figure 9] showed a very low adherence to guidelines as the diuretics represented only 20%. Fortunately, none of the interviewed physicians was prescribing BBs. It is notewothy that the above-mentioned pattern was consistent despite of the hospital type. The finding that no BB is used is somewhat promising compared to that reported in Germany, where about 10% of the physicins use BB for asthmatic or chronic obstructive pulmonary disease patients. ^[2]

Figure 9: Trends in treating hypertension associated with bronchial asthma

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Trends in treatment of hypertension associated with diabetes mellitus

In comparison to SHMG, results obtained revealed a high degree of adherence where about 80% of the physicians prescribe ACEIs or CCBs. Moreover, use of BB or diuretics was nearly negligible (less than 4%) avoiding possible interaction of such drugs with blood glucose level [Figure 10]. This observation disagrees with a study of Sipilä et al.,^[14] showing BB and diuretics as drugs of choice for treating hypertension in diabetic patients in Finland. However, it agrees with that reported by Rochefort et al.,^[20] about the limited use and safety concerns about diuretics to treat such patients in some Quebec hospitals in Canada. The observed trend was consistent among specialized and governmental hospitals with significantly higher percentage of CCBs and ARBs prescriptions in general and private hospitals (P ≤ 0.05) (data not shown). It was also evident that the overall usage of ARBs was relatively low compared to its added benefits reported in case of diabetic patients. ^[21]

Figure 10: Trends in treating hypertension associated with diabetes mellitus

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Trends in treatment of hypertension associated with angina pectoris

Hypertension is the most prevalent and significant modifiable risk factor in individuals with concomitant coronary artery disease. ^[22] The SHNG ^[1] recommend BBs as first choice to treat hypertension accompanied with angina, followed by CCBs as second choice. However, it restricted the use of direct vasodilators, alpha blockers, and some CCB that cause tachycardia which aggravates the attacks. In the present study, the most frequently used drugs in such cases were BBs followed by CCBs and then ACEIs where their prescription reached about 52%, 13%, and 10%, respectively [Figure 11]a. Therefore, the observed degree adherence to guidelines reached about 60% of cases. Similar low degree of compliance was also observed in some German hospitals in a study done by Jeschke et al.,^[2] and in Finland by Sipilä et al.,^[14] It is worth noting that about half of the prescribed CCBs were drugs known to be associated with tachycardia. More surprisingly, the contraindicated vasodilators were prescribed to in about 7.5% of cases [Figure 11]a. Despite of its low percent, such deviations could be considered as major ones and might result in serious health problems. Noticeably, the degree of incompliance was much more striking (P ≤ 0.05) in private compared with governmental hospitals, where the percentage of prescribing direct vasodilators jumped to about 20% [Figure 11]b. Similarly, this error was more significantly pronounced (P ≤ 0.05) in the general hospitals compared with specialized ones. However, the detection of such life-threatenning deviation in the specialized hospitals was unexpected [Figure 11]c. On the contrary, the very low usage of ARBs (only 2.5%) was also noticeable [Figure 11]a and disagrees with the reported added advantages of such drugs as cardioprotection in high-risk cardiac patients including postmyocardial infarction. ^[21]

Figure 11: (a) Trends in treating hypertension associated with angina pectoris in all visited hospitals, (b) in governmental versus private hospitals, (c) and in spe cialized versus general hospitals

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Trends in treatment of hypertension associated with hyperlipidemia

For hypertension associated with hyperlipidemia, the SHMG ^[1] has recommended low-dose diuretics and ACEIs as first-line therapy, while it has forbidden the utilization of BBs and high-dose diuretics which aggravate the disturbance in lipid profile.

On the one hand, results illustrated in [Figure 12] clearly indicate about 60% of physicians compliance with the above-mentioned guidelines. On the other hand, about 30% of the prescribers preferred the CCBs which are not recommended by the guidelines for such cases. More seriously, a percentage exceeding 10% of the physicians prescribes high-dose diuretics and the BBs which may result in an increased hyperlipidemia and consequently interfere with treatment. Such deviation is considered a major one since it might lead to great health problems. Such observations were consistent in all types of hospitals (data not shown).

Figure 12: Trends in treating hypertension associated with hyperlipidemia

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Conclusion and Interpretation

Prescribing is a complex behavior simultaneously affected by several factors of varying intensity; the regulations set in different guidelines constitute only one of these. ^[23] Among other things, both patients' and doctors' expectations, perceptions and experiences may affect prescribing, as do the marketing efforts of the pharmaceutical industry. ^[14] For instance, Rochefort et al.,^[20] reported a limited use of diuretics in health centers in the Canadian province of Quebec due to misperceptions about the efficacy, safety, and tolerability of these drugs among physicians.

In our study, the results indicated great degree of incompliance to SHMG. ^[1] Such deviation contrasts with that observed in other communities as reported by Jeschke et al.,^[2] who found a relatively higher degree of compliance to hypertension management guidelines in German hospitals. However, some deviations recorded in this study were major ones that might seriously affect the patient's health. For instance, some physicians prescribed direct vasodilators for angina patients which might cause reflex tacchycardia and may be fatal. On the contrary, some other deviations were minor where physicians frequently prescribed nonrecommended drugs (ignoring the first choice drugs proposed by SHMG).

Many undelying causes were suggested to be responsible for such high degree of incompliance. One prominent cause was the lack of information and awareness about the SHMG. Interestingly, the interviewed prescribers were mostly aware about the US guidelines, ^[10] followed by British, ^[9] and then WHO international guidelines ^[11] where the percentage awareness of the above-mentioned guidelines were 76%, 56%, and 28%, repectively [Figure 13]a. Despite of being aware of such guidelines, discussions with physicians revealed a very limited knowledge about their details. Surprizingly, about 90% of the physicians were not aware about the availability of national guidelines ^[1] and its details [Figure 13]a. Such lack of awareness was effectively reflected on their prescription pattern. With this regard, the present study revealed a low percentage (only 38%) of guidelines referal upon taking therapeutic decisions [Figure 13]b. Among the referred ones, the JNC7 guidelines were the first followed by the SHMG and then the BHS, where the percentage of referal reached 16%, 9%, and 8%, respectively [Figure 13]b. Instead of referening to guidelines, 62% of the interviewed physicians took their theraspeutic decisions based on other references as availability of the drugs in the hospital, the past clinical experience as well as their previous education [Figure 14].

Figure 13: Awareness of (a) and physician referral to (b) the USA guidelines (JNC7), British guidelines (BHS), European guidelines (Egyptian Hypertension Society), WHO guidelines (WHO/ISH), and Saudi Guidelines (SHMG)

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Figure 14: Bases of therapeutic decisions for treatment of hypertension among the interviewed physicians

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Another undelying cause was the impact of marketing and promotion efforts of different companies. Such efforts may dramatically shift the prescription patterns. This interpretetion agrees with that reported by Montgomery et al.,[24] who found great significant effect of the advertizing material quality on the sales and prescription trends of antihypertensive drugs. Moreover, Fretheim and Oxman ^[8] partially attributed the international variation in hypertension therapy trends to the difference in promotional activities by different companies. Despite of not being mentioned by the physicians, field observations affirmed its impact either directly by altering the prescription behavior toward the products of some big companies with strong promotion machinery or indirectly through affecting the availability of the drugs in hospitals. In this context, about 20% of the visited prescribers reported the availability of the drugs in the hospital pharmacy to be a major determinant for their therapeutic decisions regardless of guidelines [Figure 14].

On the contrary, it was also observed that there were some tendencies to cheaper drugs especially in small private hospitals. In about 5% of cases, such tendency has driven some doctors to disobey the guidelines to consider the economic conditions of some patients [Figure 14]. This finding agrees with that reported by Fretheim and Oxman ^[8] as one cause of prescription variation.

Recommendations

Based on the findings of this study, it is recommended to arrange awareness campaigns and continued medical education activities about the SHMG among physicians in the western region. Upon arranging such programs, the personalized approach and posttraining monitoring should be considered to realize more effective campaigns. In agreement with that, previous studies suggested that personal feedback should be given to physicians in order to achieve change in prescribing practices. ^[25],[26] Similarly, it is reported that general awareness efforts and outreach visits, as well as audit and feedback usually exert a small positive impact on changes in prescription practices. ^[27],[28] In addition to awareness activities reviewing hospital drug lists to be harmonized with guidelines as well as setting hospital regulations that control prescription patterns is highly recommended as effective tools to promote compliance to hypertension management guidelines.

References

1.	Saudi Hypertension Management Group. Saudi Hypertension Management Guidelines. 2 ^nd ed. 2006.
2.	Jeschke E, Ostermann T, Vollmar HC, Kröz M, Bockelbrink A, Witt CM, et al. Evaluation of prescribing patterns in a German network of CAM physicians for the treatment of patients with hypertension: A prospective observational study. BMC Fam Pract 2009;10:78-91.
3.	Chrostowska M, Narkiewicz K. Improving patient compliance with hypertension treatment: Mission possible? Curr Vasc Pharmacol 2010;8:804-7. [PUBMED]
4.	Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: The VALUE randomised trial. Lancet 2004;363:2022-31. [PUBMED]
5.	SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-64. [PUBMED]
6.	Bøg-Hansen E, Lindblad U, Ranstam J, Melander A, Råstam L. Antihypertensive drug treatment in a Swedish community: Skaraborg Hypertension and Diabetes Project. Pharmacoepidemiol Drug Saf 2002;11:45-54.
7.	Fretheim A, Aaserud M, Oxman AD. The potential savings of using thiazides as the first choice antihypertensive drug: Cost-minimisation analysis. BMC Health Serv Res 2003;3:18. [PUBMED]
8.	Fretheim A, Oxman AD. International variation in prescribing antihypertensive drugs: Its extent and possible explanations. BMC Health Serv Res 2005;5:21. [PUBMED]
9.	Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, et al. Guidelines for management of hypertension: Report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens 2004;18:139-85. [PUBMED]
10.	The Seventh Report of the Joint National Committee (JNC7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. U.S. Department of Health And Human Services, National Institutes of Health, National High Blood Pressure Education Program, NIH Publication No. 03-5233; 2003.
11.	Whitworth JA. World health organization, international society of hypertension writing group. 2003 world health organization (WHO)/international society of hypertension (ISH) statement on management of hypertension. J Hypertension 21:1983-92.
12.	Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the management of arterial hypertension: The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007;28:1462-536. [PUBMED]
13.	Musini VM, Rezapour P, Wright JM, Bassett K, Jauca CD. Blood pressure lowering efficacy of loop diuretics for primary hypertension. Cochrane Database Syst Rev 2012;8:CD003825. [PUBMED]
14.	Sipilä R, Helin-Salmivaara A, Korhonen MJ, Ketola E. Change in antihypertensive drug prescribing after guideline implementation: A controlled before and after study. BMC Fam Pract 2011;12:87.
15.	Smith JP, Lewis JB. Hypertension management: Special considerations in chronic kidney disease patients. Curr Hypertens Rep 2004;6:462-8. [PUBMED]
16.	Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: A network meta-analysis. JAMA 2003;289:2534-44. [PUBMED]
17.	Turnbull F. Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: Results of prospectively-designed overviews of randomised trials. Lancet 2003;362:1527-35.
18.	Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: Meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009;338:b1665. [PUBMED]
19.	Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database Syst Rev 2009;3:CD001841. [PUBMED]
20.	Rochefort CM, Morlec J, Tamblyn RM. What differentiates primary care physicians who predominantly prescribe diuretics for treating mild to moderate hypertension from those who do not? A comparative qualitative study. BMC Fam Pract 2012;13:9. [PUBMED]
21.	Ferdinand KC, Taylor C. The management of hypertension with angiotensin receptor blockers in special populations. Clin Cornerstone 2009;9:S5-17. [PUBMED]
22.	Ismail H, Makaryus AN. Management of hypertension in patients with coronary artery disease. Expert Rev Cardiovasc Ther 2011;9:1271-7. [PUBMED]
23.	Denig P, Haaijer-Ruskamp FM, Zijsling DH. How physicians choose drugs. Soc Sci Med 1998;27:1381-6.
24.	Montgomery BD, Mansfield PR, Spurling GK, Ward AM. Do advertisements for antihypertensive drugs in Australia promote quality prescribing? A cross-sectional study. BMC Public Health 2008;8:167.
25.	Figueiras A, Sastre I, Gestal-Otero JJ. Effectiveness of educational interventions on the improvement of drug prescription in primary care: A critical literature review. J Eval Clin Pract 2001;7:223-41. [PUBMED]
26.	Soumerai SB, McLaughlin TJ, Avorn J. Improving drug prescribing in primary care: A critical analysis of the experimental literature. Milbank Q 1989;67:268-317. [PUBMED]
27.	O'Brien MA, Rogers S, Jamtvedt G, Oxman AD, Odgaard-Jensen J, Kristoffersen DT, et al. Educational outreach visits: Effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2007;4:CD000409 . [PUBMED]
28.	Jamtvedt G, Young JM, Kristoffersen DT, O'Brien MA, Oxman AD. Audit and feedback: Effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2006;2:CD000259. [PUBMED]