11 August 2011
A meta-analysis of observational studies found that, compared with patients prescribed diuretics and beta-blockers, patients prescribed angiotensin II receptor antagonists (A2RAs) were around twice as likely to adhere to treatment. Although adherence to A2RAs was significantly higher than adherence to ACE inhibitors, the difference was smaller and may have been due to publication bias.
Level of evidence:
Level 3 (limited quality patient-oriented evidence) according to the SORT criteria.
Healthcare professionals should follow NICE guidelines on medication adherence and on the management of hypertension (due to be updated in August 2011). Patients should be involved in the initial decision to prescribe antihypertensives (and other medicines) and reviewed regularly to explore their experience of using the medication and offer support to encourage adherence. Healthcare professionals should note that, in this study, rates of adherence to antihypertensive treatment were suboptimal for all drug classes. However, there were differences between drug classes, for example, adherence to A2RAs and ACE inhibitors was higher than for other drug classes.
What is the background to this?
Poor adherence to antihypertensives is an important cause of poor blood pressure control and has been associated with complications, such as increased cardiovascular events.
Adherence to medication in clinical trial settings may not be representative of adherence in real world settings. For example, in the ALLHAT study, at year 1, adherence to antihypertensives ranged from 83% to 88% whereas adherence to antihypertensives in observational studies has generally been much lower.
Although there appear to be differences in adherence between antihypertensive drug classes, individual observational studies are difficult to compare because of differences in patient populations, drug class comparisons and definitions of adherence. Therefore, the clinical relevance of any differences is unclear. This meta-analysis (15 studies) aimed to quantify the overall association between antihypertensive drug class and adherence in clinical settings in order to provide evidence to help guide the selection of an antihypertensive.
What does this study claim?
This study found that pooled mean adherence ranged from 28% for beta-blockers to 65% for angiotensin II receptor blockers (A2RAs). Although ACE inhibitors appeared to have the second best level of adherence, followed by calcium channel blockers (CCBs), insufficient data were available for definitive ranking.
Adherence to A2RAs was statistically significantly higher than adherence to other drug classes: ACE inhibitors (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.13 to 1.57), CCBs (HR 1.57, 95%CI 1.38 to 1.79), diuretics (HR 1.95, 95%CI 1.73 to 2.20), and beta-blockers (HR 2.09, 95%CI 1.14 to 3.85). Adherence to diuretics was statistically significantly lower than adherence to other drug classes. However, after publication bias was accounted for, there was no longer a significant difference between A2RAs and ACE inhibitors, or between diuretics and beta-blockers. Similarly, the relative benefit of adherence to A2RAs compared with ACE inhibitors was more pronounced in pharmaceutical-affiliated studies compared with non-pharmaceutical affiliated studies.
The study has several limitations. Firstly, the authors point out that A2RAs were prescribed at lower rates than are currently typical in developed countries, which may have biased the comparisons between A2RAs and other drug classes. Also, it is possible that adherence to A2RAs may be related more to patient selection factors than to the drug class itself. The authors state that, until this is assessed, it is premature to recommend A2RAs first-line for minimising adherence problems. Secondly, thirteen of the studies only included patients who were starting their first antihypertensive drug, therefore the findings may not be generalisable to people who are already taking one or more antihypertensives. Thirdly, there was significant heterogeneity when data were pooled.
Nevertheless, the results of the study consistently showed that, in clinical settings, there are differences in adherence to antihypertensive drug classes, with highest adherence to A2RAs and ACE inhibitors and lowest adherence to diuretics and beta-blocker. Subgroup analyses supported the robustness of the overall conclusions.
Healthcare professionals should note that adherence was suboptimal regardless of drug class (range 28% to 65%) and pay attention to adherence, even when prescribing an A2RA or ACE inhibitor.
NICE guidance on medication adherence offers best practice advice on how to involve patients in decisions about prescribed medicines and how to support adherence. It also recommends that the initial decision to prescribe medicines, the patient’s experience of using the medicines and the patient’s needs for adherence support should be reviewed regularly.
NICE guidance on the management of hypertension states that patients should be provided with an annual review of care to monitor blood pressure, offer support and discuss lifestyle, symptoms and medication. Listening to patients’ views about the pros and cons of treatment for hypertension, involving patients in each stage of the management of their condition and providing clearly written supportive information is good clinical practice. This NICE guideline is currently being updated and expected to be published in August 2011.
Design: Meta-analysis of 15 observational studies which assessed adherence to antihypertensives as an outcome, between 1989 and 2004. A qualitative analysis was also performed on 17 studies.
Patients: 935,920 community-dwelling patients aged 18 years or over were included in the 17 studies in the qualitative analysis. Two pairs of studies included overlapping data and were excluded from the quantitative meta-analysis. In the 15 studies used in the meta-analysis, the pooled mean age of patients was 61.7 years. 53.1% were women. Pooled mean person-months of adherence observation across studies was 12.3 months.
Intervention and comparison: Included studies compared adherence between at least two different antihypertensive drug classes.
Outcomes: Hazard ratios and odds ratios were pooled separately. Hazard ratios were selected as the primary measure of relative adherence.
Pooled mean adherence:
- A2RAs 64.9% (95%CI 64.3% to 65.6%)
- ACE inhibitors 57.6% (95%CI 57.2% to 57.9%)
- CCBs 52.0% (95%CI 51.6% to 52.5%)
- diuretics 51.0% (95%CI 51.4% to 51.8%)
- beta-blockers 28.4% (95%CI 28.1% to 28.8%).
Adherence to A2RAs was statistically significantly higher than adherence to other drug classes:
- ACE inhibitors HR 1.33 (95%CI 1.13 to 1.57)
- CCBs HR 1.57 (95%CI 1.38 to 1.79)
- diuretics HR 1.95 (95%CI 1.73 to 2.20)
- beta-blockers HR 2.09 (95%CI 1.14 to 3.85).
After accounting for publication bias, there was no statistically significant difference in adherence between A2RAs and ACE inhibitors (HR 1.10, 95%CI 0.94 to 1.30). Also, the difference between A2RAs and ACE inhibitors did not remain significant when studies were restricted to those measuring adherence as therapy persistence. The relative benefit of adherence to A2RAs compared with ACE inhibitors was more pronounced in pharmaceutical-affiliated studies (HR 1.41, 95%CI 1.17 to 1.70) compared with non-pharmaceutical affiliated studies (HR1.09, 95%CI 1.06 to 1.11).
Adherence to diuretics was statistically significantly lower than adherence to other drug classes:
- A2RAs HR 1.95 (95%CI 1.73 to 2.20)
- ACE inhibitors HR 1.78 (95%CI 1.60 to 1.97)
- beta-blockers HR 1.26 (95%CI 1.01 to 1.59)
- CCBs HR 1.50 (95%CI 1.20 to 1.87).
After accounting for publication bias, there was no statistically significant difference in adherence between beta-blockers and diuretics (HR 1.13, 95%CI 0.89 to 1.44).
The same pattern was present when odds ratios were pooled. The qualitative analysis also showed broadly similar results.
Sponsorship: Grants from the National Heart, Lung and Blood Institute and the National Institute of Diabetes, Digestive, and Kidney Diseases
For e-learning materials on adherence see the Patients and their medicines: adherence to treatment and developing concordance skills section of the NPC website. Further information on hypertension can be found on NHS Evidence and in the hypertension e-learning materials.
Please comment on this rapid review using our feedback form.
Make sure you are signed up to NPC Email updates — the free email alerting system that keeps you up to date with the NPC news and outputs relevant to you