Antihypertensive medication adherence and blood pressure control among central Alabama veterans

Abstract

Medication nonadherence is associated with adverse outcomes. To evaluate antihypertensive medication adherence and its association with blood pressure (BP) control, the authors described population adherence to prescribed antihypertensive medication (proportion of days covered ≥80%) and BP control (mean BP <140/90 mm Hg) among central Alabama veterans during the fiscal year 2015. Overall, 75.1% of patients receiving antihypertensive medication were considered adherent, and 66.1% had adequate BP control. Patients adherent to antihypertensive medication were more likely to have adequate BP control compared with patients classified as nonadherent (67.4% vs 62.0%; adjusted odds ratio 1.33; 95% confidence interval, 1.22–1.44 [P<.0001]). Among patients who had uncontrolled BP, 73.6% were considered adherent to medication. Adherence to antihypertensive medication was associated with adequate BP control; however, a substantial proportion of patients with inadequate BP control were also considered adherent. Interventions to increase BP control could address more aggressive medication management to achieve BP goals.

1. Introduction

Medication adherence generally refers to whether patients take their medication as mutually agreed when prescribed by a healthcare provider and whether they continue to take prescribed medication.1 Adherence to prescribed medication leads to better health outcomes, fewer emergency department visits and hospitalizations, decreased mortality, and lower healthcare costs.2, 3, 4, 5, 6 Previous studies indicate that approximately half of patients prescribed antihypertensive medication discontinue therapy within 1 year of initiation.1, 7 Patients are more likely to stop taking medications for chronic, asymptomatic conditions (such as hypertension) because side effects might be experienced without perceived benefit of symptomatic relief.8 Among participants in the National Health and Nutrition Examination Surveys during 2001–2010, only about half with hypertension had controlled blood pressure (BP). Some of those with uncontrolled BP were not under medication therapy; however, 40% of treated hypertensive patients also had inadequate control of BP.9 Nonadherence to prescribed medication likely played a role in lack of BP control.10, 11, 12 We described antihypertensive prescribing, medication adherence, and the relationship between adherence and BP control at a regional Veterans Affairs healthcare system to establish a baseline reference before planning an interdisciplinary, pharmacist‐led program to improve medication adherence and BP management.

2. Methods

2.1. Population

Existing electronic health record data from the Central Alabama Veterans Health Care System (CAVHCS) were abstracted for all outpatients (adult veterans enrolled in care with CAVHCS serving central Alabama and portions of western Georgia) who were dispensed at least one antihypertensive medication during federal fiscal year 2015 (October 1, 2014, through September 30, 2015).

2.2. Measures

We calculated mean population adherence to antihypertensive medication using the proportion of days covered methodology endorsed by the Pharmacy Quality Alliance and National Quality Forum.13 For each veteran, adherence was defined as having ≥80% of days covered by an antihypertensive medication from the date of first antihypertensive prescription fill to the end of the fiscal year or date of death during the fiscal year. Antihypertensive medication classes included were β‐blockers (BBs), thiazide diuretics (including thiazide‐like and thiazide‐type medications), calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and medications with fixed combinations of the drug classes above. Antihypertensive agents of each class are available on the CAVHCS formulary, thus prescribers’ options are not limited by class; however, particular agents within a class may be restricted to certain uses. For example, losartan is on the approved formulary but is restricted to patients who are unable to tolerate ACEIs. Other ARBs are approved only on a case‐by‐case basis for patients with heart failure. Combination formulations of antihypertensives are rarely used at CAVHCS because few are on the approved formulary. One example of an approved combination formulation is lisinopril/hydrochlorothiazide, which is available on the local formulary and not restricted to particular patients. If date ranges of prescription fills for the same class of antihypertensive medication overlapped, the refill start date was adjusted to the day the previous fill ended. In addition to overall antihypertensive medication adherence, single‐class adherence for each class was determined by calculating the mean proportion of days covered with antihypertensive medication among patients receiving only the one class of medication during the fiscal year.

Additional data abstracted from the electronic health record included age, mean weight, mean height, and mean of last three (or fewer than three if not available) systolic and diastolic BP measurements. BP control was defined as mean recorded measurements <140 mm Hg systolic and <90 mm Hg diastolic. BP measurements obtained retrospectively from the electronic records were measured, recorded, and acted upon by the providing clinician per routine, usual care. Automated devices are available and typically used for BP measurement, but there is no standard protocol for obtaining routine BP measurement. Persons with missing BP values were excluded from analysis of BP control in bivariate and multivariable analysis. Body mass index (BMI) was calculated from height and weight as kg/m² after excluding implausible values; persons missing BMI values were excluded from the regression model. BP values were missing for 914 patients (5.1%), and BMI values were missing for 3734 patients (20.9%). Only deidentified data were abstracted from existing electronic records. The analysis was designed to describe a baseline reference before planning a pilot program to improve medication adherence and BP control for the CAVHCS population and thus deemed nonresearch by the CAVHCS Office of Research Oversight.

2.3. Statistical analysis

All analyses were performed with SAS version 9.4 (SAS Institute Inc, Cary, NC). Bivariate associations were assessed by chi‐square and two‐tailed t test with statistical significance set at P<.05. Logistic regression analysis for adjusted odds ratios and 95% confidence intervals (CIs) modeled BP control (dependent variable) with either adherence as a dichotomous variable or proportion of days covered as a continuous variable, and included age, BMI, number of antihypertensive medication fills, and number of antihypertensive drug classes as likely confounders.

3. Results

For the fiscal year 2015, there were 33 different antihypertensive medications dispensed in seven drug class categories through 79 178 outpatient prescriptions to 17 889 unique patients in the CAVHCS system (Table 1). The mean number of unique antihypertensive medication classes dispensed per patient was 1.8 (median 2, range 1–6), with an average of 4.4 prescription fills for each patient during the fiscal year (median 4, range 1–30), covering a mean of 83.5 days per prescription (median 90, range 1–90). Of the patients, nearly half (45.2%) received only one class of antihypertensive medication, 35.4% received two different classes, 16.0% received three classes, and 3.5% received four or more classes. Among all patients receiving some type of antihypertensive agent, 52.5% received an ACEI, 40.0% a CCB, 38.8% a BB, 37.5% a thiazide diuretic, and 13.1% an ARB, summing over 100% because each patient might have received multiple classes of antihypertensives (Table 1). For all antihypertensive medication fills, the top five medications dispensed were lisinopril, amlodipine, hydrochlorothiazide, metoprolol, and losartan, accounting for 76.2% of all fills. The top five classes dispensed were ACEIs (26.8%), CCBs (23.0%), BBs (22.4%), thiazides (17.7%), and ARBs (7.4%), with the remainder combinations of ACEIs/thiazides (2.7%) or BBs/thiazides (0.01%).

Table 1.

Dispensed Outpatient Antihypertensive Medications by Patient and Medication Fill—Central Alabama Veterans Health Care System, Fiscal Year 2015

Antihypertensive Class	Patients, %	Medication Fills, %
	N=17 889	N=79 178
Angiotensin‐converting enzyme inhibitor (ACEI)	52.5	26.8
Calcium channel blocker	40.0	23.0
β‐Blocker	38.8	22.4
Thiazide diuretic	37.5	17.7
Angiotensin receptor blocker	13.1	7.4
ACEI/thiazide combination formulationa	5.7	2.7
β‐Blocker/thiazide combination formulationa	0.01	0.01
Missing	0.32	0.09

^aCombination formulation components included separately in each of the medication classes listed above.

Percentages sum to >100% because each patient may have been prescribed multiple classes of medication.

Among patients receiving at least one antihypertensive medication, the mean age was 63.3 years (range 21–115), mean systolic BP was 133.6 mm Hg (range 80–229), mean diastolic BP was 78.3 mm Hg (41‐132), and mean BMI was 30.7 kg/m² (12.8–92.0) (Table 2). Of all persons with BMI available, 82.8% had a BMI in the overweight or obese category (BMI ≥25). Overall, 75.1% of patients met criteria for being considered adherent to medication (at least 80% of eligible days covered with an antihypertensive medication) (Table 2). The mean proportion of eligible days covered by antihypertensive medication for all patients was 86.5% (median 97.9%, range 0.7%–100%). Adherent patients had a higher proportion of days covered than nonadherent patients (P<.001). Small but statistically significant (P<.001) differences between the adherent and nonadherent groups were noted in mean BP, age, and BMI, as well as proportion classified as overweight or obese. Adherence did not vary substantially by antihypertensive class (classes ranged from 87.4% to 90.5% of days covered for 76.8%–82.4% of patients considered adherent), with regimens that included an ARB having the highest proportions of days covered and adherence compared with other drug classes.

Table 2.

Characteristics of Patients by Antihypertensive Medication Adherence and Blood Pressure Control—Central Alabama Veterans Health Care System, Fiscal Year 2015

Characteristics	Overall	Adherent	Nonadherent	Controlled	Noncontrolled
Patient, No. (%)	N=17 889 (100)	n=13 432 (75.1)	n=4457 (24.9)	n=11 224 (66.1)	n=5751 (33.9)
Age, mean (range), y	63.3 (21–115)	63.9 a (24–104)	61.5 a (21–115)	63.2 (21–104)	63.5 (24–100)
Body mass index (range), kg/m2	30.7 (12.8–92.0)	30.8 a (12.8–92.0)	30.2 a (14.2–72.0)	30.8 b (12.8–92.0)	30.5 b (14.3–78.7)
Overweight or obese, %	82.8	83.7 a	79.9 a	83.9 b	80.7 b
Adherence
Adherent to antihypertensive medication, %	75.1	100	0	78.0 b	73.6 b
Days covered with antihypertensive (range), %	86.5 (0.7–100)	96.6 a (80–100)	56.2 a (0.7–79.9)	88.1 b (0.7–100)	86.2 b (1.5–100)
Control
Blood pressure controlled, %	66.1	67.4 a	62.0 a	100	0
Systolic blood pressure, mean (range), mm Hg	133.6 (80–229)	133.2 a (80–215)	135.0 a (81–229)	124.8 b (80–139)	150.9 b (111–229)
Diastolic blood pressure, mean (range), mm Hg	78.3 (41–132)	77.9 a (42–132)	79.7 a (41–125)	75.3 b (41–89)	84.3 b (49–132)

Bold values indicate statistical significance. ^a P<.05 for adherent vs nonadherent. ^b P<.05 for controlled vs noncontrolled.

Overall, 66.1% of patients receiving antihypertensive medications were considered to have adequate BP control (with a mean systolic pressure <140 mm Hg and mean diastolic <90 mm Hg) (Table 2). Between patients with controlled BP and those with uncontrolled BP there was a significant and meaningful difference in BP (systolic mean 124.8 vs 150.9 mm Hg, P<.0001), but no substantial difference in BMI (30.8 vs 30.5, P=.012) or age (63.2 vs 63.5 years, P=.23). Patients with controlled BP had a significantly higher mean proportion of days covered with an antihypertensive medication than those with uncontrolled BP (88.1% vs 86.2%, P<.0001). Among those with uncontrolled BP, 73.6% were considered adherent to medication, compared with 78.0% adherent among those with controlled BP (P<.0001). In bivariate analysis, patients considered adherent to antihypertensive medication were 1.09 (95% CI, 1.06–1.12) times more likely to have adequate BP control compared with patients considered nonadherent (67.4% vs 62.0%, P<.0001).

Among patients taking only a single class of antihypertensive throughout the fiscal year, 67.4% of patients were considered adherent and 70.1% had controlled BP. Single‐class adherence was highest for ARBs (75.6%) and lowest for BBs (64.7%) (Figure). Despite the low adherence, single‐class BBs had the highest BP control (76.2%) of all single‐class regimens. Among patients taking only a single class of antihypertensive and also considered adherent to medication, 72.0% had controlled BP. The following is the proportion of patients with controlled BP who were adherent to single‐class regimens by drug class: BBs 77.8%, thiazides 74.4%, ACEIs 73.5%, CCBs 67.0%, and ARBs 66.2%. For patients taking only a single class and who were adherent, the likelihood for control using a BB was 1.10 (95% CI, 1.06–1.15; P<.0001) times greater compared with those taking some other class of antihypertensive.

Figure 1.

Single‐class medication adherence and blood pressure (BP) control—Central Alabama Veterans Health Care System, Fiscal Year 2015. ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, β‐blocker; CCB, calcium channel blocker; Thiazide, thiazide diuretic. Error bars indicate 95% confidence interval

In a logistic regression model controlling for age, BMI, number of antihypertensive medication fills, and number of antihypertensive drug classes (Table 3), the adjusted likelihood of having BP control was 1.33 (95% CI, 1.22–1.44) times higher for patients adherent to BP medication compared with those who were nonadherent. Substituting the proportion of days covered during the fiscal year in the model as a continuous variable instead of the dichotomous adherence variable (also controlling for age, BMI, number of medications filled, and number of drug classes), a higher proportion of days covered was associated with a 1.9‐fold higher likelihood of having BP control (95% CI, 1.57–2.31; P<.0001).

Table 3.

Logistic Regression Models for Blood Pressure Control—Central Alabama Veterans Health Care System, Fiscal Year 2015

Covariate	Adjusted Odds Ratio	95% Confidence Interval	P Value
Dichotomous adherence model
Adherence, yes or no	1.33	1.217–1.442	<.0001
Age, y	1.00	0.997–1.003	.85
Body mass index, kg/m2	1.01	1.004–1.015	.002
No. of antihypertensive medication fills	1.04	1.019–1.052	<.0001
No. of antihypertensive classes	0.71	0.672–0.755	<.0001
Continuous adherence model
Adherence, proportion of days covered	1.90	1.571–2.305	<.0001
Age, y	1.00	0.997–1.003	.85
Body mass index, kg/m2	1.01	1.004–1.015	.002
No. of antihypertensive medication fills	1.04	1.019–1.052	<.0001
No. of antihypertensive classes	0.71	0.670–0.752	<.0001

Bold values indicate statistical significance (P<.05).

4. Discussion

In a review of electronic health records from a Veterans Affairs healthcare system, we found that two thirds of outpatients who were dispensed antihypertensive medication achieved BP control. Likelihood of achieving target BP among patients treated with antihypertensive medications was 1.3‐fold higher for those considered adherent to prescribed antihypertensive medication compared with patients who had <80% of eligible days covered by antihypertensive medication. For patients who did not attain target BP, nearly three quarters were considered adherent to prescribed antihypertensive medication, suggesting that factors other than medication adherence also contribute to hypertension control.

Our finding of 75% overall adherence and 33% improvement in adjusted likelihood of having BP control by medication adherence is remarkably similar to a study of managed care organizations in which 75% of patients on monotherapy were adherent, and adherent patients were 45% more likely to achieve BP control (odds ratio 1.45).14 In the study by Bramley and colleagues,14 only 43% of adherent patients reached BP goals; in their study, low level of BP control was attributed to “clinical inertia” in which healthcare providers failed to titrate medication or to combine medications when encountering a patient with elevated BP. Failure to adjust antihypertensive medication in more than three quarters of visits where elevated BP was recorded has been previously reported.10 In addition, patients were only included in the study by Bramley and colleagues if they were taking a single antihypertensive agent (including a fixed‐dose combination formulation). Observing high adherence with low levels of BP control in patients receiving monotherapy supports the concept that although simplified medication regimens increase adherence, some patients might require more than one class of antihypertensive medication to adequately control BP. Inclusion in our analysis of patients taking multidrug regimens might account for the higher rate of observed overall BP control (66%). Although combination formulations were not often prescribed in our setting at CAVHCS, analysis included patients taking more than one medication. Despite availability, combination formulations were not often prescribed, perhaps because the individual medications were added at different times in the course of treatment and consideration was not often given to adding it as a combination tablet. Combination therapy and multidrug regimens can facilitate achievement of BP goals. A national health survey found that increased use of multiple antihypertensive agents (from 36.8% prevalence in 2001–2002 to 47.7% in 2009–2010) was associated with a 55% increased likelihood of BP control for patients taking combination formulations and a 26% increased likelihood of control for patients taking multiple agents.9 Providers should strive to balance encouraging medication adherence through simplified medication regimens with assuring effective BP control. Adherence can be encouraged by prescribing a minimum number of medications, use of combination formulations when possible, selection of long‐acting agents to achieve the fewest required daily doses, and choosing medications with favorable side effect profiles, but vigilance for adequate BP control should be maintained with close monitoring and more aggressive medication therapy management if BP control is inadequate.7, 8, 11, 15, 16

Clinic office processes can facilitate medication adherence by utilizing mail‐order or automated refill systems and limiting barriers to refills by having low copayments and minimizing other out‐of‐pocket costs to patients.1, 8, 17 To avoid clinical inertia, practices could have protocols to actively recognize patients with elevated BP, intensify treatment to maximize BP control, and schedule return visits to monitor their pressures.7, 8, 11, 15, 18, 19 Practices might consider offering complimentary office BP checks without an appointment and adopting a hypertension treatment algorithm based on current recommendations to guide BP management.8, 15, 18, 19

Of course, the burden of improving adherence and BP control does not fall solely on the primary care provider. Team‐based care can involve other clinic personnel or other allied health professionals such as nurses, pharmacists, dieticians, and social workers.7, 8, 18, 20, 21, 22, 23 A systematic review of quality improvement strategies for hypertension management found that interventions that incorporated a team approach (such as creation of multidisciplinary teams, addition of new team members, change of roles, and case or disease management) were associated with the largest improvements in BP.23 Studies have shown that nursing staff can improve BP control by providing telephone support for home self‐monitoring of BP, patient education, health coaching, and potentially even medication adjustment under physician supervision.24, 25, 26, 27 Pharmacists can have a greater role in providing patient education, individual counseling, and medication therapy management.17, 21, 22, 27, 28, 29, 30 A recent Community Preventive Services Task Force guide statement recommended team‐based care to improve BP control.20, 31 Evidence from 80 studies of team‐based care interventions showed that the proportion achieving BP control increased by a median of 12.0 percentage points, noting that teams including pharmacists had considerably greater improvements. The best results were obtained when team members were authorized to change antihypertensive medications either independently or with oversight of the primary care provider. Viswanathan and colleagues17 systematically reviewed interventions to improve medication adherence and outcomes for chronic diseases. For hypertension, blister packaging, case management, and education with behavioral support all improved medication adherence, while case management and face‐to‐face education provided by pharmacists had the best evidence for enhanced medication adherence leading to decreased BP. Hirsch and associates22 found that pharmacy medication therapy management not only lowered systolic BP by 7 mm Hg after 6 months (compared with an increase of 1.6 mm Hg in the usual care group) but also reduced primary care visits. In their study, the most common medication therapy gaps identified were need for additional agents and dosage increases. Nurse‐led clinics for BP control have been shown to be a good value, with cost‐effectiveness estimated at $4020 per quality‐adjusted life‐years.25 In a systematic review, the median cost of 20 included studies of team‐based care interventions was estimated at $284 per patient annually, while the seven studies with complete accounting that focused only on BP cost $225 per patient.32 Although pharmacy costs have been shown to increase with improved adherence (increasing by an average of $429 per patient annually for hypertension medication), total healthcare spending was significantly lower for adherent patients (by $4337), leading to an average cost‐benefit ratio of 1:10.1 for hypertension.5 To follow the baseline analysis presented here, CAVHCS plans to design and implement a pharmacist‐led multidisciplinary patient education program with antihypertensive therapy management for improved antihypertensive medication adherence and BP control.

4.1. Strengths and Limitations

A strength of this evaluation is that CAVHCS is a closed system with patients primarily receiving medications from one source, thus we are likely to capture a majority of medication fills for this population. Receiving care through a Veterans Affairs facility, however, might limit the generalizability of our results. Compared with other healthcare settings, copay requirements are minimal to none for patients at CAVHCS, reducing financial factors as a contributor to nonadherence. In addition, availability of mail order for filling medication at CAVHCS lowers barriers for obtaining medication (and thus facilitates medication adherence); however, mail order might not be an option in other health systems. Comparability between medication adherence assessments can be problematic with different methods used. As with other studies using the methodology of the proportion of days covered, medication fills were used to calculate medication adherence, but estimates might be somewhat inflated if all dispensed medication is not actually consumed by the patient. Previous studies indicated, however, that pharmacy‐dispensing data correlated with objective measures of medication consumption such as serum drug levels or physiologic effects.33 Another potential limitation of this method is the assumption that failure to refill medication is a result of nonadherence by the patient when instead the medication might have been discontinued by the treating provider or switched to a less common secondary antihypertensive not included in this analysis (eg, an α₂‐agonist such as clonidine or direct vasodilator such as hydralazine). We have attempted to mitigate for medication regimen changes by measuring adherence to any of the most common classes of antihypertensive medication rather than specific drugs in case healthcare providers switch drugs or classes, but not all medications with potential effects on BP were included in the analysis. No attempt was made to verify a diagnosis of hypertension among patients dispensed an antihypertensive agent. Some patients might have been prescribed a medication with antihypertensive effects for reasons other than management of BP (such as a BB or CCB for control of heart rate or ACEI for renal protection), thus some patients might be included who did not have a diagnosis of hypertension. An additional limitation is that the analysis did not account for patients who might have moved out of the area or sought care or medication through other sources during the measurement period, which would falsely lower estimated adherence. Lastly, insufficient data were available to account for factors that might have a role in the relationship between medication adherence and BP control such as sex, family medical history, comorbid conditions (eg, history of myocardial infarction, diabetes, or stroke), severity of illness, tobacco or alcohol use, illicit drug use, or socioeconomic status. The magnitude of effect of this final limitation is uncertain; however, neither sociodemographic nor clinical characteristics have been found to serve as clinically useful predictors of refill adherence in patients with hypertension.34

5. Conclusions

Adherence to antihypertensive medication is associated with improved control of BP, but medication adherence alone is not sufficient for all treated patients to achieve BP targets. Healthcare providers should encourage patients to take medication as prescribed, closely monitor patients’ BP, and intensify medication therapy when target BPs are not met. Beyond the examination room encounter, team‐based approaches could be instituted such as pharmacist‐led or nurse‐managed patient education, monitoring, counseling, and medication adjustment. Treatment of patients with hypertension lowers the risk for serious complications and improves health outcomes, but works best when healthcare providers maximize medication adherence and recognize and manage patients with inadequate BP control.

Conflict of Interest

None of the authors have any conflicts of interest to disclose.

Disclaimer

The findings and conclusions in this journal article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Piercefield EW, Howard ME, Robinson MH, Kirk CE, Ragan AP, Reese SD. Antihypertensive medication adherence and blood pressure control among central Alabama veterans. J Clin Hypertens. 2017;19:543–549. 10.1111/jch.12953