Adherence With Lipid-Lowering, Antihypertensive, and Diabetes Medications

Hypertension, dyslipidemia, and diabetes mediate cardiovascular disease in many patients, and patients with 2 or 3 of these conditions face the greatest risks.¹ All 3 conditions are potentially controllable with medications.^2-4 A number of studies have demonstrated associations between good adherence and lower risks in routine care settings. One study, for example, reported that patients taking medications for hypertension for 80% or more of the days of supply attained substantially improved blood pressure control compared with patients who adhered 50% or less of the time.⁵ A second study reported that appropriate drug treatment for blood pressure reduced the incidence of stroke by 30% to 40% and the incidence of myocardial infarction by 20% to 25%.⁶ A report on lipid-lowering medications estimated that patients with good adherence reduced their serum levels more than patients with poor adherence (30% vs 11%).⁷ Ho et al observed that patients with diabetes who had good medication adherence had fewer all-cause hospitalizations and reduced mortality.⁸

Despite the accepted importance of high medication adherence as expressed in national guidelines, patients often take medications irregularly, or start and subsequently stop their medications.^9-11 The chronic nature of hypertension, dyslipidemia, and diabetes coupled with the absence of overt symptoms and the costs of medications may contribute to the low adherence. One study of statins for cholesterol control found that only about 60% of patients had high adherence 12 months after starting treatment.¹² Only 26% of the patients remained adherent after 5 years. A study of hypertension medications in 13 managed care organizations reported that a fourth of patients taking drugs for hypertension did not maintain high adherence.13 A review of studies of patients with diabetes reported drug adherence ranging from 36% to 93% depending on the population and the type of medication.¹⁴

A still unresolved issue is whether patients taking a greater number of medications have increased or decreased adherence. Some studies found patients taking more medications were less adherent,^12,15,16 whereas other studies reported that patients taking more medications had the highest adherence.^17-20 Patients with multiple conditions that require long-term management face the greatest challenge in maintaining adherence.

In this study we investigated patients taking medications for hypertension, dyslipidemia, and diabetes. The study population consisted of patients who took drugs for 1 or more of the conditions and who were enrolled with the largest insurer in Hawaii between 2004 and 2008. The objectives were to investigate by the combinations of medications patients were taking (1) trends in adherence over time, (2) relative medication adherence, and (3) the consistency of individual patient adherence from year to year.

METHODS

The study population consisted of patients enrolled with the largest insurer in Hawaii who had hypertension, dyslipidemia, and/or diabetes and who filled a prescription for a medication for 1 or more of the 3 conditions between 2004 and 2008. The insurer covers approximately 650,000 lives, or about half of the state’s nonmilitary population. The study used existing data without patient identifiers and was granted an exemption from review by the University of Hawaii Institutional Review Board.

As a primary outcome, we calculated medication possession ratios, which were defined as the proportion of days enrolled in a year that were covered by a filled prescription. Medical possession ratios were calculated separately for medications for hypertension, dyslipidemia, and diabetes. If more than 1 prescription for a condition was filled on the same day, the day was counted only once toward the numerator. Patients with a medical possession ratio of 80% or higher were considered adherent. This definition has often been used in studies of drug adherence and has been shown to measure adherence with medications that require long-term use.²¹ With administrative data, however, filled prescriptions do not necessarily mean continuous use, as patients may not take all of their purchased medications. Patients were included in analyses for calendar years in which they had no more than a 45-day gap in enrollment. This choice was made to measure adherence among patients enrolled long enough to reflect their usual adherence during the year.

The analyses included regression models adjusted for multiple variables that might explain difference in adherence by the combinations of medications taken. Age, sex, island of residence, and morbidity were included to adjust for patient characteristics. Morbidity was also measured, based on claims submitted during a calendar year using the Johns Hopkins Adjusted Clinical Groups Case-Mix System (www.acg.jhsph.edu). Calendar year was included to adjust for possible temporal trends. Health plan was adjusted for, so that members within the same health plan would be compared.

For analyses, the frequency of adherence was summarized by year and by the combinations of the medications taken. Analyses also summarized the proportion of patients adherent in the current year by whether or not they had been adherent in the past year. Adherence adjusting for patient characteristics was modeled using negative binomial regression to provide relative risks. Interaction terms between age and morbidity with medication cohorts were included in some regression models. Regression models were fit using generalized estimating equations to correct for correlations among repeated measurements within people. Most patients had multiple years of adherence data. The same methodology was used to model adherence in the current year as a function of adherence in the previous year.

RESULTS

A total of 148,119 people qualified for the study. At the start of their first year in the study the population was primarily 35 years and older. Only 2.5% were aged 20 to 34 years, whereas 20.1% were aged 35 to 49 years, 38.7% were aged 50 to 64 years, and 38.7% were 65 years and older. Slightly over half (51.7%) were female, and the majority (73.3%) lived on Oahu, the most populous of the Hawaiian Islands. About one-third had a high morbidity index (32.6%), and 21.6% had heart disease. In their first year in the study, 48.2% of patients were taking medications for a single illness (32.4% antihypertensive medications, 19.7% lipid-lowering medications, and 6.1% medications for diabetes). Of the other participants, 21.8% were taking antihypertensive and lipid-lowering medications, 5.7% were taking antihypertensive and diabetes medications, 3.3% were taking lipid-lowering and diabetes medications, and 11.1% were taking antihypertensive, lipid-lowering, and diabetes medications.

Between 2004 and 2008 the percentage of patients who adhered with medications for hypertension, hyperlipidemia, and diabetes remained nearly constant (

Figure

). Adherence with the individual medications, however, varied from less than 65% to nearly 80% by the combinations of other medications taken. More patients were adherent to diabetes medications than to other medications, and the fewest patients were adherent to lipid-lowering medications. Adherence with antihypertensive medications was intermediate. Among patients taking a particular medication such as an antihypertensive medication, however, adherence varied by what other medications they were taking. Among patients using medications to lower lipid levels, for example, those also taking medications for both hypertension and diabetes had the highest adherence, followed by patients taking hypertensive and lipid-lowering medications. The next highest adherence rate was among patients taking diabetes and lipid-lowering medications, followed by patients taking only medications to control their lipid levels.

As a general observation, patients taking 1 of the 3 types of medication had higher adherence if they also were taking a second type of medication, and the highest adherence if they were taking all 3 types. A group with especially low adherence was patients taking diabetes medications alone; their adherence averaged less than 60%.

The observed differences in adherence might have resulted from demographic factors such as older patients having more prescriptions and being more prone to take their medications. To address this possibility, we analyzed associations between the medications taken and adherence with adjustment for patient characteristics (

Table 1

). The order of adherence by combinations of medications after adjustment remained the same as that observed in the unadjusted frequencies. Of the adjusted results, the highest relative risks occurred with diabetes medications as a consequence of the especially low adherence of the

reference group, patients who were taking medications only for diabetes.

Other analyses examined possible differences in the strengths of associations by comparing members within medication cohorts by age group (65 years and older versus younger ages) and by high compared with low morbidity. The older patients within a medication cohort tended to be adherent less frequently. As an example of one of the stronger differences, patients with hypertension, hyperlipidemia, and diabetes who were younger than 65 years had 11% higher adherence than older patients (95% confidence interval [CI] 8%, 19%). Patients with low morbidity tended to be adherent less frequently than those with high morbidity. For example, patients with hypertension, hyperlipidemia, and diabetes and low morbidity had 8% lower adherence than patients with high morbidity (95% CI 6%, 10%). More than half of the differences by age and morbidity, however, were less than 5%, and not all were statistically significant.

Adherence was examined further by measuring the consistency of adherence of individual patients from year to year (

Table 2

). Results mirrored the results for adherence by calendar year in several respects. Patients taking medicines for more conditions were less likely to stop adherence in the next year if they had been adherent in the past year, and more likely to start adherence if they had not been adherent in the past year. The most favorable pattern was evident among patients taking medications for hypertension, hyperlipidemia, and diabetes. The percentage of patients remaining adherent if they had been adherent in the past year by the various medications taken ranged from 64% to 88%. The percentages for becoming adherent if they had been nonadherent in the past year ranged from 17% to 47%.

Changes in adherence from year to year were examined further in regression models adjusted for patient characteristics (

Table 3

). Patients taking lipid-lowering, antihypertensive, and diabetes medications together were the least likely to stop adhering with any of the medications. Patients taking medications for a single illness were the most likely to stop. Among patients nonadherent in the past year, the largest percentage who did adhere in the current year were those taking all 3 medications and the smallest percentage were those taking medications for a single illness. As with adherence, the strength of associations within medication cohorts was examined by comparing younger and older ages and high versus low morbidity. The only consistent pattern observed was for patients taking medications for diabetes. Healthier members were less likely to become adherent if they had been nonadherent in the past year and more likely to become nonadherent if they had previously been adherent. The magnitude of differences ranged from 10% to 19%.

DISCUSSION

Our results show first that patients had a lower average adherence with lipid-lowing medications than with antihypertensive medications, and had the highest average adherence with medications for diabetes. Trends over time were relatively flat, exhibiting only minor fluctuations regardless of the combinations of medications taken. Among patients taking medications for the same illness, adherence was better when they were also taking medications for 1 or 2 of the other illnesses. Patients taking medications for hypertension, dyslipidemia, and diabetes had the highest adherence. Especially for hypertension and diabetes, patients may often be managing more than 1 medication for the condition simultaneously, although adherence was defined as 1 or more filled prescriptions on a given day. Adherence by combinations of the medications being taken remained in an order that persisted across the study years. The relative rates of adherence by the combinations of medications prescribed remained in the same order after adjusting for patient characteristics.

Patients were more likely to be adherent in the current year if they had adhered in the past year, as one might expect. The extent to which patients stayed adherent from year to year, however, varied by the combinations of prescribed medications, as did the percentage of patients who were nonadherent in the past year and became adherent in the current year. The more illnesses for which patients were taking medications, the more likely they were both to become adherent if nonadherent in the past and to stay adherent if adherent in the past.

A number of other studies have also reported that patients taking more medications have higher adherence. These studies typically investigated adherence with single medications and examined adherence by the total number of other drugs that patients were taking. A study of new users of statins to control lipid levels, for example, found that the more medications patients were taking at the initiation of statin therapy, the better their daily medication adherence.¹⁸ A second study of new statin users observed that patients with a greater medication burden had higher medical possession ratios.¹⁷ A study of newly diagnosed hypertensive patients found those taking multiple drugs for other conditions had better adherence with their antihypertensive medications.

²²

Contrary to these examples, other studies have observed that patients with a greater medication burden have lower adherence. One study of lipid-lowering drugs among patients 65 years and older reported patients with the highest number of medications in the past year had the lowest adherence.¹⁶ A study of patients initiating therapy with both antihypertensive and lipid-lowering medications found that patients taking 6 or more medications were about half as adherent as patients taking 1 or no medication. Adherence in this study was higher with antihypertensive medications than with lipid-lowering medications,¹⁵ a finding similar to ours. A second study of patients initiating concomitant antihypertensive and lipid-lowering therapy reported that adherence among patients taking 0, 1, and 2 other medications was 41%, 35%, and 30%, respectively.²³

The studies that examined adherence by the number of medications taken differ from one another in a number of ways. Some, for example, included all patients taking the study medications, whereas others only enrolled new users. The demographic characteristics of the study populations also varied, as did the medications examined for adherence. As a further issue, the other medications being taken by patients in the studies may have differed, and typically were not characterized. Any combination of these factors may have contributed to the discordant results.

We took the approach of studying adherence specifically among patients for the 3 most common conditions leading to cardiovascular disease. The results suggest patients taking medications for more of the conditions maintained higher adherence. Patients with more chronic illnesses may have a greater sense of vulnerability and a stronger belief that taking medications may protect them from serious adverse events.²⁴ Patients in poor health especially may feel at risk compared with patients with risk factors but without overt disease. One study reported that elderly patients with a history of stroke, congestive heart failure, or hypertension had high statin adherence.¹² The issue of adherence by patient morbidity, however, is likely complex; for example, having a coronary event has been associated with subsequent discontinuation of preventive medications.²⁵ As a further issue, patients taking medications for multiple illnesses may experience drug interactions between drugs in the same category or between drugs in different categories. The relationship of polypharmacy, adherence, and the outcome of polypharmacy requires further study. Patients with more illnesses or greater severity of a single illness may see physicians more often, which in turn may affect medication adherence. Some patients may cut their pills in half to reduce expenses, and this practice might vary by the number of illnesses.

This article has a number of limitations that affect interpretation of the results. The study population only included members of a single insurer in Hawaii, so the results may not generalize to other populations. Patients included in analyses had filled at least 1 prescription during the calendar year; patients who stopped their medication use before the start of a year were excluded. Given the chronic nature of the conditions, however, most patients included in the analyses would be long-term users. The definition of adherence as 80% of days with prescriptions is arbitrary, although a choice frequently used in studies of medication adherence.

It is likely some patients obtained free samples from their physicians; if so, these medications would not be included in the insurer’s pharmacy data. If patients taking medications for more illnesses were more likely to obtain free samples, a bias might result. The severity of illnesses among patients with similar illnesses might affect adherence. If any patients had additional drug insurance with a different insurer, prescriptions billed to the other insurer would not have been known. A further issue is that patients taking multiple medications for the same illness but who failed to fill a prescription for 1 of their medications would be counted as being adherent in this study, although not necessarily following their doctor’s orders. Finally, adherence was based on filled prescriptions; the extent to which patients actually took their medications was unknown.

Our primary conclusion is that patients taking medications for more of the 3 conditions studied (hypertension, dyslipidemia, diabetes) have greater adherence than patients taking medications for fewer of the conditions. With medications for more illnesses, the proportion of patients who adhered in a calendar year was higher, the proportion who became nonadherent if adherent in the previous year was lower, and the proportion who become adherent if they had been nonadherent in the previous year was higher. The results suggest that physicians should not be concerned about negatively affecting adherence by prescribing medications for 2 or all 3 of these conditions. Confirmation of the findings in other populations would strengthen this conclusion.

Of concern is the lower adherence of patients taking drugs for 2 of the 3 conditions, and the especially low adherence among patients with single illnesses. Patients taking medications for single illnesses may require education and support to encourage their medication adherence. Patients with a low frequency of adherence to multiple medications also warrant attention. They face the greatest immediate risks of cardiovascular and other adverse events. The constancy of the trends in adherence across the 5 years of the study emphasizes, however, how difficult changing adherence behavior may be, as well as the importance of developing new intervention strategies.