Journal of Human Hypertension (2006) 20, 295–297 & 2006 Nature Publishing Group All rights reserved 0950-9240/06 $30.00 www.nature.com/jhh
RESEARCH LETTER
Adherence to antihypertensive medication and association with patient and practice factors Journal of Human Hypertension (2006) 20, 295–297. doi:10.1038/sj.jhh.1001981; published online 19 January 2006
Medical non-adherence has previously been identified as a major problem in the treatment of hypertension. In our study, we found a mean adherence of 91.44711.62% and no significant associations were discovered between adherence to medication and socio-demographic variables, comorbidities or number of antihypertensive drugs taken. Further research is needed to identify effective interventions to enhance patient medication adherence for this prevalent chronic condition. Hypertension is an important risk factor for cardiovascular disease. Despite improvements in its detection and treatment since the 1970s, studies show that 60–75% of treated hypertensive patients do not reach the recommended target blood pressure of o150/90 mmHg.1,2 Non-adherence is thought to be a factor in lack of control of blood pressure and may lead to unnecessary adjustments of drug regimens and increased health care costs.3 Studies suggest that a treatment’s efficacy is attenuated by patient non-adherence with medication and lifestyle advice. In fact, it has been estimated that only 50% of patients take medication as prescribed.4 The present study investigated adherence to antihypertensive treatment in a primary care population of hypertensive patients. The study was carried out in the population of Tayside in Scotland. Data were collected in conjunction with a study that examined organisational factors in primary care that influence blood pressure control.5 Prescription data were obtained from the Medicine Monitoring Unit’s record linkage database. This database contains several data sets including all dispensed community prescriptions, hospital discharge data, biochemistry results, and other data that are linked by a unique patient identifier, the community health number (CHI). These data are made anonymous for the purposes of research and the methods used are approved by the Tayside Caldicott Guardians. The project was approved by the Tayside committee on research medical ethics. The study population was 511 patients who were resident in Tayside and registered with a general practitioner in the eight study practices. All patients were diagnosed as hypertensive on their GP clinical
system (General Practice Administration System for Scotland (GPASS)) READ code and were prescribed one or more antihypertensive drugs between January 2000 and January 2002. The primary outcome was percentage adherence. Adherence relates to ability and willingness to abide by a prescribed therapeutic regimen. For each prescription we knew the strength of the tablet, the number of tablets dispensed, and the instructions on how these should be taken. Thus, the daily dose and the number of days’ treatment could be calculated. Adherence to treatment was calculated as the number of days with treatment supply divided by the total number of days from the first prescription to the end of the study period. If a patient collected more drug than they had been directed to use, the percentage of adherence was over 100% but we classified these subjects as having maximum adherence. We assessed the relationship between adherence to dispensed medication and the explanatory variables of age, sex, social deprivation category, years since diagnosis, comorbidity, general practice site and number of antihypertensive drugs prescribed. Data were summarised as number of subjects (percentages) for categorical variables. Odds ratios and 95% confidence intervals were used to investigate the magnitude of the association between each explanatory variable and the outcome of adherence (X80%). Data were managed and analysed using Stata 8.0 Statistical Software. There were 511 patients in this study, of which 439 (85.9%) had greater than 80% adherence. Of those, 134 (26.2%) of patients were classed as having 100% adherence. The mean adherence of the 511 patients was 91.44%. A substantial proportion of patients, 202 (39.5%) were in the least affluent deprivation categories (5–6). Just over half, 272 (53%) did not have a concurrent comorbidity recorded, whereas 77 (15%) had two or more. The most prevalent comorbidities were angina (15.9%) and diabetes mellitus type 2 (20%). No significant associations were discovered between percentage adherence X80% and sex, age, deprivation scores, years since diagnosis, comorbidity or practice (Table 1). In general, the practice site did not have an effect on a patients’ adherence; however, practice 2 had a significant association compared to practice 1, with a greater odds of X80% adherence. This was a prespecified subgroup analysis therefore chance is the most likely explanation.
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Table 1 Associations between patient characteristics and percentage adherence Demographic
Percentage Percentage adherence adherence o80%, n (%) X80%, n (%)
Odds ratio
95% CI
Sex Male Female
32 (13) 40 (15)
210 (87) 229 (85)
1 0.87
0.53–1.44
Age (years) 40–49 50–59 60–69 70–79
6 12 27 27
(24) (15) (15) (12)
19 66 156 198
(76) (85) (85) (91)
1 1.74 1.82 2.32
0.57–5.30 0.66–5.01 0.84–6.36
Deprivation category 1 6 (19) 2 7 (9) 3 8 (11) 4 12 (10) 5 5 (23) 6 34 (19)
26 67 67 114 17 146
(81) (91) (89) (90) (77) (81)
1 2.21 1.93 2.19 0.78 0.99
0.67–7.31 0.60–6.19 0.74–6.45 0.20–3.02 0.38–2.60
Years since diagnosis 0–4 years 13 (14) 5–9 years 18 (14) 10–14 years 18 (15) 15+ years 22 (14)
80 115 104 135
(86) (86) (85) (86)
1 1.04 0.94 0.99
0.48–2.24 0.43–2.03 0.48–2.09
No. of comorbidities 0 41 (15) 1 24 (15) 2+ 7 (9)
231 (85) 138 (85) 70 (91)
1 1.02 1.77
0.59–1.76 0.76–4.15
(84) (95) (89) (81) (83) (91) (75) (90)
1 3.96 1.48 0.78 0.91 1.86 0.57 1.70
1.01–15.60 0.52–4.21 0.31–1.95 0.35–2.33 0.63–5.51 0.23–1.38 0.57–5.05
No. of antihypertensive drugs prescribed 1 16 (11) 125 (89) 2 32 (17) 155 (83) 3+ 24 (13) 159 (87)
1 0.62 0.85
0.32–1.19 0.43–1.67
Practice 1 2 3 4 5 6 7 8
10 3 7 13 11 6 16 6
(16) (5) (11) (19) (17) (9) (25) (10)
53 63 55 54 53 59 48 54
Odds ratio41 ¼ association with greater percentage adherence; o1 ¼ association with poorer percentage adherence.
Over three quarters of patients, 370 (72.4%) were prescribed more than one antihypertensive drug. Diuretics 328 (61%) were the most commonly prescribed followed by ACE inhibitors 259 (48%). In addition to antihypertensive medication, 168 (31%) were prescribed lipid-lowering therapy and 170 (32%) aspirin. A substantial minority 45 (8%) of patients was prescribed other non-steroidal anti-inflammatory drugs. No significant association was discovered between percentage adherence X80% and number of antihypertensive drugs taken (OR ¼ 0.85, 95% CI 0.43–1.67 for patients on more than three drugs compared with those on one drug). This study shows that approximately 85% of patients with hypertension adhere to their medication Journal of Human Hypertension
regime, when defined by the X80% adherence cutpoint. This finding suggests that adherence to antihypertensive medication is higher than previously described in the context of randomised controlled trials.6,7 Gender, age, deprivation status, years since diagnosis, and number of comorbidities did not have an affect on a patients adherence (Table 1). In contrast to evidence from systematic reviews of randomised controlled trials of adherence enhancing strategies, increasing numbers of drugs were not associated with worse adherence to antihypertensive medication. In a recent meta-analysis of eight studies and 11 485 observations, it was reported that the average adherence for once-daily dosing was significantly higher than for multiple daily dosing (91.4 versus 83.2%, respectively, Po0.001).8 Similarly, another systematic review of randomised controlled trials showed an improvement in adherence through the use of once-daily instead of twice-daily dosage regimens.7 Several factors have been proposed as affecting medication adherence in hypertensive patients: patient demographics, side effects of medication, convenience of drug dosing, cost and number of medications, patients’ knowledge, beliefs and attitudes about hypertension and its treatment, patients’ involvement with their care, and health care system issues.9 This observational study suggests that the independent effect of some of these factors is not likely to be substantial. The adherence goal of 80% of prescribed dose is used conventionally in clinical trials of safety and efficacy.10 A recent systematic review identified 25 trials in which adherence with antihypertensive medications was measured with electronic monitors to determine whether there was a relationship between adherence and rate of blood pressure control.6 However, analysis of the trials showed inconsistent results in the majority of cases and concluded that there was no convincing evidence of poor adherence resulting in inadequate blood pressure. Dispensed prescribing was used as the method for assessing drug adherence. This is one of several methods available for measuring adherence to drug treatments, both direct and indirect, all of which have advantages and disadvantages.11 Dispensed prescribing through record linkage has the advantage of being an efficient method for measuring adherence to drug treatment in large population studies. Unlike clinical trials, which focus mainly on men and the young, population based record linkage studies allow real world populations to be studied. It is assumed that if a prescription is filled then patients would adhere to treatment but there is no way of knowing whether patients actually took their treatment. This problem is not unique and in fact applies to the vast majority of adherence studies including randomised controlled trials. The patient population selected composed a prevalent population of hypertensive subjects. It may be possible that incident/newly diagnosed patients may have poorer
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adherence levels and this group require further investigation. The results of this study suggest that patients are generally adherent to their antihypertensive medication and that socio-demographic factors, comorbidities and medication regime do not affect a patients’ ability to adhere to their medication. Although poor adherence is assumed to be an important explanation for inadequate blood pressure control, the relationship between patient compliance and hypertension has not yet been properly established.6 Recognizing and understanding the role of patient non-adherence as a factor leading to poor blood pressure control and adverse outcomes remains a key challenge for clinicians caring for patients with hypertension.
What is known on this topic? K Control of hypertension is often inadequate, with a substantial proportion of patients failing to reach treatment goals. K Non-adherence is thought to be a major factor in inadequate control of blood pressure. What this study adds? K In a prevalent population of hypertensive subjects, patients are generally adherent to their antihypertensive medication. K Socio-demographic factors, comorbidities, and medication regime did not affect a patients’ ability to adhere to their medication.
ME Inkster1, PT Donnan1, TM MacDonald2, FM Sullivan1 and T Fahey1 1 Tayside Centre for General Practice, University of Dundee, Kirsty Semple Way, Dundee, UK and 2 Medicines Monitoring Unit (MEMO), University of Dundee, Kirsty Semple Way, Dundee, UK E-mail:
[email protected] Published online 19 January 2006
References 1 Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the US. N Engl J Med 2001; 345: 479–486. 2 Wolf-Maier K, Cooper RS, Kramer H, Banegas JR, Giampaoli S, Joffres MR et al. Hypertension treatment and control in five European countries, Canada, and the US. Hypertension 2004; 43: 10–17. 3 Van Wijk BLG, Klungel OH, Heerdink ER, de Boer A. The association between compliance with antihypertensive drugs and modification of antihypertensive drug regimen. J Hypertens 2004; 22: 1831–1837. 4 Haynes RB, McDonald HP, Garg AX. Helping patients follow prescribed treatment: clinical applications. JAMA 2002; 288: 2880–2883. 5 Inkster M, Fahey T, Montgomery A, Donnan P, MacDonald T, Sullivan F. Organisational factors in relation to control of blood pressure; an observational study. Br J Gen Pract 2005; 55: 931–937. 6 Wetzels GEC, Nelemans P, Schouten JS, Prins MH. Facts and fiction of poor compliance as a cause of inadequate blood pressure control: a systematic review. J Hypertens 2004; 22: 1849–1855. 7 Schroeder K, Fahey T, Ebrahim S. How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled trials. Arch Intern Med 2004; 164: 722–732. 8 Iskedjian M, Einarson TR, MacKeigan LD, Shear N, Addis A, Mittmann N et al. Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin Therap 2002; 24: 302–316. 9 Krousel-Wood M, Thomas S, Muntner P, Morisky D. Medication adherence: a key factor in achieving blood pressure control and good clinical outcomes in hypertensive patients. Curr Opin Cardiol 2004; 19: 357–362. 10 Sackett DL, Haynes RB, Gibson ES, Hackett BC, Taylor DW, Roberts RS et al. Randomised clinical trial of strategies for improving medication compliance in primary hypertension. Lancet 1975; 1: 1205–1207. 11 Osterberg L, Blaschke T. Drug therapy: adherence to medication. N Engl J Med 2005; 353: 487–497.
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