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Hypertension. 1995;25:1045-1051

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(Hypertension. 1995;25:1045-1051.)
© 1995 American Heart Association, Inc.

Articles

Trends in Medication Choices for Hypertension in the Elderly

The Decline of the Thiazides

Mark Monane; Robert J. Glynn; Jerry H. Gurwitz; Rhonda L. Bohn; Raisa Levin; Jerry Avorn

From the Program for the Analysis of Clinical Strategies, Gerontology Division, and the Preventive Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; and the Claude Pepper Geriatric Research and Training Center, Harvard Medical School, Boston, Mass.

Correspondence to Mark Monane, MD, MS, Program for the Analysis of Clinical Strategies, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115.


*    Abstract
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 *Abstract
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 down arrowMethods
 down arrowResults
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Abstract We studied the evolution in choice of antihypertensive therapy in the elderly over a seven-year period and defined factors associated with such prescribing. To accomplish this, we performed a retrospective analysis of 8428 enrollees older than 65 years of age in the New Jersey Medicaid and Medicare programs newly begun on antihypertensive therapy between 1982 and 1988. Diuretics were the most common agents prescribed (51%), followed by calcium channel blockers (14%), ß-blockers (13%), central adrenergic antagonists (11%), and angiotensin-converting enzyme inhibitors (5%). However, the use of diuretics declined sharply during the latter part of the time interval studied. Using logistic regression modeling, we determined that the odds of a subject being started on a diuretic compared with any other antihypertensive drug decreased from 1.0 during the referent years 1982 to 1984 to 0.75 in 1985 to 1986 and to 0.41 in 1987 to 1988, after controlling for demographics, comorbidity, and hospital and physician visits (P<.001). The relative odds of diuretic use were significantly increased (P<.05) for the oldest subjects (odds ratio, 1.28 for age 85 and older versus ages 65 to 74 odds), women (odds ratio, 1.15), and blacks (odds ratio, 1.14). Despite the growing evidence during the study interval of the efficacy of diuretics in treating hypertension in the elderly, diuretic use diminished throughout this period in relation to other antihypertensive drugs. Subject characteristics (oldest subjects, women, and blacks) were important determinants of physicians' choice of antihypertensive therapy.


Key Words: aging • antihypertensive agents • diuretics • elderly • epidemiology


*    Introduction
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 *Introduction
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 down arrowResults
 down arrowDiscussion
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More than half of the population older than 65 years of age has hypertension, the most important reversible risk factor for cardiovascular complications such as myocardial infarction and stroke. Nonetheless, surprisingly little attention has been focused on the gerontological aspects of hypertension research.1 Treatment of hypertension is the most common reason for patients to visit a physician and to receive medications.2 3

The selection of the most appropriate therapy for a given patient remains a controversial issue. The Joint National Committee (JNC) report in 19774 and 19805 recommended a step care approach using diuretics as initial therapy; in 1984,6 ß-blockers were added to the list. The 1988 JNC report7 recommended thiazides or ß-blockers in addition to calcium channel blockers (CCBs) or angiotensin-converting enzyme (ACE) inhibitors for first-line therapy in the management of hypertension. More recent studies have affirmed the role of treating isolated systolic hypertension as well as elevated blood pressure in those individuals older than 80.8 9 10 11 12 Current recommendations (JNC 1993) have renewed emphasis on the use of thiazides and ß-blockers as first-line agents, unless there are special indications for other drugs.13 14

About half of patients with hypertension will respond to monotherapy with a low to moderate dose of any of the more than 100 available agents.15 16 17 18 However, diuretics and ß-blockers (and, to a lesser extent, reserpine) are the only drugs that have been shown to prevent the long-term consequences of essential hypertension; such outcomes data for CCBs and ACE inhibitors have not been studied adequately. Costs for antihypertensive medication, 70% to 80% of the total expenditure for treating hypertension,14 19 range from $5 per year for thiazides to more than $1400 per year for an ACE inhibitor.20

Surveys performed in two New England communities,21 among Tennessee Medicaid elderly,22 and using a national prescription database23 during the early 1980s found that the prevalence rates of diuretics and ß-blockers declined markedly, with sharp increases in CCBs and ACE inhibitors. In a recent study by Psaty et al24 involving a large community sample of elderly patients, new users of antihypertensive agents were about 40% less likely to receive a diuretic or ß-blocker. Despite this previous work, an information gap remains on overall antihypertensive use in the elderly. Most of these studies covered a time period before the formal introduction of CCBs and ACE inhibitors. Little information is available on incident antihypertensive use, which is important as it represents the physician's initial therapeutic decision; while the Psaty study did examine incident treatment, it covered a 1-year period only (1990 to 1991) and thus was unable to examine changes in incidence over time.

Our objectives were to examine the choice of initial antihypertensive therapy from 1982 through 1988 among a population-based sample of elderly subjects and to define factors associated with such prescribing in the elderly. We focused on drugs prescribed for newly diagnosed cases of hypertension because of our interest in the initial choice of therapy rather than switching patterns among the various antihypertensive drugs.


*    Methods
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 *Methods
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Sources of Data
The study population was drawn from the New Jersey Medicaid and Medicare programs for the years 1982 through 1988. We studied this interval because of the availability of complete and accurate data from the New Jersey Medicaid and Medicare programs during this 7-year span. For all data, personal identifiers were removed from claims records, with individuals represented only by untraceable code numbers. Demographic characteristics including age, gender, and race as well as data on nursing home residency and date of death were ascertained from the Medicaid enrollment file. Medication use information was extracted from the Medicaid paid claims pharmacy file, representing all prescriptions filled for outpatients and nursing home residents. Each pharmacy record contains information on the dispense date, National Drug Code (NDC) number, quantity dispensed, number of days supplied, cost, pharmacy identification number, and prescriber identification number.

Prior hospital and nursing home stays in subjects older than age 65 were defined by linking Medicaid data to Medicare claims (parts A and B). All outpatient physician visits were also identified for the population studied, along with information regarding dates of each visit and the provider identification number.

Selection of Study Subjects
We first identified all participants in the New Jersey Medicaid program aged 65 or older who filled a prescription for any antihypertensive medication between 1982 and 1988. The date of the first prescription for any antihypertensive medication was defined as the index date. New users of antihypertensive medications were required to have previously filled no prescriptions for an antihypertensive agent; drug claims were searched back to 1981 to ensure that study subjects had not previously filled a prescription for this drug category. We required that each study subject have continuous Medicaid eligibility in the 12 months preceding and 12 months following the first antihypertensive claim. Active system use was further required as reflected in the filling of any prescription for at least one drug of any kind during the periods 1 to 119 days and 120 to 365 days before and after the index date. We excluded subjects initiated on multiple antihypertensive drugs on the index date (n=484). These criteria defined a cohort of new antihypertensive users that included 8428 study subjects.

For the purposes of this study, antihypertensive medications were divided into the following categories: thiazide and related diuretics, ß-adrenergic blockers, CCBs, ACE inhibitors, central adrenergic agonists, peripheral adrenergic antagonists, and vasodilators (eg, hydralazine and minoxidil). We also collected information on patient demographics such as age, gender, and race. We measured health services–related variables such as year of initiation of antihypertensive therapy as well as total number of prescriptions filled, and comorbidity variables such as number of physicians visited and hospital or nursing home admission.

Statistical Analysis
Study subjects were characterized according to the initial antihypertensive drug therapy received. The frequency of antihypertensive use was measured using simple descriptive techniques in terms of drug class and individual generic entity. For the outcome of diuretic initiation, we used {chi}2 tests for categorical variables and t tests for continuous variables. In addition, we estimated the relative risk of initiation of diuretic therapy through the odds ratio (OR) calculated with unconditional logistic regression25 using the SAS CATMOD program26 and derived 95% confidence intervals for the ORs and significance tests for differences from the null value using the estimated standard errors.27 Binary variables were calculated with a 0/1 classification in all testing.28 Tests for possible interactions among independent variables were performed.29

Potential predictors of diuretic use in the logistic regression model included age (65 to 74, 75 to 84, 85 years and older), race (white, black, other), gender, and year of initiation of therapy (1982 to 1984, 1985 to 1986, 1987 to 1988). As noted, descriptions of intensity of medical care in the 120 days before the first antihypertensive prescription included number of prescriptions filled (0 to 3, 4 to 7, 8 or more), number of physician visits (0 to 3, 4 to 7, 8 or more), and hospital or nursing home stay.


*    Results
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Subject Characteristics
Table 1 summarizes the characteristics of the study population (n=8428). Subjects had a mean age of 77 years, with approximately one fifth of the population 85 years and older, and were predominantly female. Whites represented 68% of the population; blacks accounted for 16%.


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  		Table 1. Characteristics of the Study Population Taking Antihypertensive Medications

These subjects were active users of the health care system in the 120 days before the first antihypertensive prescription. Over this 120-day period, the average number of different prescriptions filled was approximately seven. Subjects made an average of more than three visits to physicians, and more than a third had either a hospital or nursing home stay during this interval.

Secular Trends in Antihypertensive Choices
As a whole, diuretics were the most commonly prescribed initial agents, accounting for 4321 (51%) of first prescriptions, followed by CCBs (14%), ß-adrenergic blockers (13%), central adrenergic agonists (11%), ACE inhibitors (5%), peripheral adrenergic antagonists (4%), and vasodilators (2%). However, examination of trends of new prescriptions of antihypertensive medication over the 7-year study interval demonstrated marked changes in the frequency of use of each drug class (Fig 1). The proportion of prescriptions for diuretics decreased from 59% of all new antihypertensive agents in 1982 to 33% by 1988. During this period, there was a fourfold increase in prescriptions for CCBs (7% to 28%). A similar increase occurred in the prescription of ACE inhibitors (0.3% in 1982 to 2% in 1984 to 16% in 1988), which were indicated for hypertension management in 1984. The proportion of first prescriptions for ß-blockers did not change essentially throughout the study period, although there was a clear switch from noncardioselective ß-blockers to cardioselective agents: the proportion of prescriptions for propranolol decreased from 8.3% in 1982 to 5.3% in 1988, and initial prescriptions for the cardioselective drugs atenolol and metoprolol increased from 2.8% to 4.4%.



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  		Figure 1. Graph shows frequency distribution of new prescriptions for antihypertensive agents by class for each year over the study interval 1982 through 1988. CCBs indicates calcium channel blockers; B-BLOCKERS, ß-adrenergic blockers; ACE INHIB, angiotensin-converting enzyme inhibitors; PERIPH ANTAG, peripheral adrenergic antagonists; and VASODIL, vasodilators.

As indicated in Fig 2, the decreased use of diuretics as first-line therapy occurred at the same time as the appearance of several key articles in the peer-reviewed literature confirming the efficacy of this class of drugs to treat hypertension in elderly as well as in nonelderly populations.



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  		Figure 2. Graph shows proportion of new antihypertensive prescriptions for diuretics by year in relation to the publication of peer-reviewed articles in the literature. Studies presented to the left of the graph were published before the 1982 to 1988 interval examined in the present article. Abbreviations to the left: VA indicates Veterans Administration Cooperative Study Group on Antihypertensive Agents (1967)30 ; JNC I, Joint National Committee Report on Detection, Evaluation, and Treatment of High Blood Pressure (1977)4 ; USPHS, US Public Health Service Hospitals Cooperative Study Group (1977)31 ; HDFP, Hypertension Detection and Follow-up Program Cooperative Group (1979)32 ; JNC II, Joint National Committee Report on Detection, Evaluation, and Treatment of High Blood Pressure (1980)5 ; OSLO, Oslo Study (1980)33 ; and AUST, Australian Therapeutic Trial in Mild Hypertension (1981).34 Abbreviations within the graph: HDFP indicates Hypertension Detection and Follow-up Program Cooperative Group (1982)35 ; VA, Veterans Administration Cooperative Study Group on Antihypertensive Agents (1982)36 ; JNC III, Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (1984)6 ; EWPHE, European Working Party on High Blood Pressure in the Elderly Trial (1985)37 ; MRC, Medical Research Council Working Party (1985)38 ; WG, Working Group on Hypertension in the Elderly (1986)39 ; COOPE, Coope and Warrender (1986)40 ; WIKSTRAND, Wikstrand et al (1986)41 ; and JNC IV, Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (1988).7

Factors Related to Antihypertensive Choice
We found significant relationships between several independent variables and diuretic use after adjusting for potential confounding through logistic regression modeling (Table 2). Older age was associated with greater diuretic use: the oldest subjects (those 85 and older) were 1.28 times more likely (P<.0001) than those 65 to 74 to be initiated on a diuretic agent. Women were more likely than men to receive diuretics (OR 1.15, P<.001). Race was another important factor determining diuretic use: while whites and those subjects classified as "other" (mostly Hispanic) had comparable rates of diuretic initiation, blacks were more likely (OR 1.14, P<.05) to be prescribed a diuretic.


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  		Table 2. Odds Ratio for the Initiation of Diuretic Therapy

The strongest predictor of diuretic use was year of initiation of antihypertensive therapy, with declining trends noted throughout this time interval. Compared with the referent years 1982 to 1984, the odds of starting a diuretic were 0.75 (P<.0001) in 1985 to 1986 and 0.41 (P<.0001) in 1987 to 1988. These figures are adjusted for demographics, nursing home and hospital stay, and number of physician visits and medications in the drug regimen.

In some of the subjects studied, several of the drugs may have been used primarily to treat coronary artery disease or congestive heart failure rather than hypertension. We therefore repeated the analysis after removing all subjects with any evidence of diagnoses or drug treatments for either of these two disorders; this resulted in 4424 remaining new users of antihypertensive medication. Trends in diuretic use among this cohort were very similar to those seen in the larger group of antihypertensive users: the odds of diuretic initiation were 0.83 (P<.0001) in 1985 to 1986 and 0.42 (P<.0001) in 1987 to 1988 versus the referent years 1982 to 1984. Other significant associations with diuretic use remained essentially unchanged as well.


*    Discussion
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 up arrowAbstract
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 up arrowResults
 *Discussion
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Efficacy, side effects, and cost considerations are key components of decision making in prescribing an antihypertensive agent. Thiazide and related diuretics have the longest and best-established track record of all antihypertensive drugs.16 While effective in treating high blood pressure,42 43 44 45 46 CCBs and ACE inhibitors have not been subjected to the same large-scale, long-term clinical trials required to demonstrate their efficacy in preventing stroke and other cardiovascular end points in the elderly or any other age group.47 Despite this, over the period studied, thiazides declined from 59% of all new antihypertensive prescriptions in 1982 to 33% in 1988. ß-Blocker use remained relatively constant, despite the capacity of these drugs to reduce cardiovascular morbidity and mortality in trials involving thousands of hypertensive individuals.33 38 48 Subject characteristics were also important determinants of physicians' choice of antihypertensive therapy. The oldest subjects were more likely to receive a diuretic agent, as were women and blacks.

During the 1980s, substantial changes occurred in attitudes about and approaches to the treatment of hypertension in the elderly. At the beginning of the decade, newly diagnosed elderly hypertensive patients were far less likely to receive any treatment than their middle-aged counterparts.22 Reasons for hesitation in initiating treatment included concern about increased side effects of antihypertensive drugs in the elderly and skepticism about the value of such treatment, because early clinical trials included few elderly patients. However, during this period, results of the Hypertension Detection and Follow-up Program,32 35 49 Australian trial,34 and European Working Party on High Blood Pressure in the Elderly study37 as well as other studies30 31 33 36 38 40 41 50 indicated the benefits of treating elevated diastolic pressure in the elderly. More recently, the National Blood Pressure Education Program Working Group Report on Hypertension in the Elderly released guidelines for clinicians, including the use of diuretic therapy as the preferred initial drug unless there is a reason to favor other agents.51 Yet, the prescribing patterns we have documented do not conform to the regimens used in the above-mentioned trials or the recommendations of the JNC reports published in 1977,4 1980,5 and 19846 or the Working Group on Hypertension in the Elderly.39 While the 1988 consensus7 expanded the first-line treatment options to include CCBs and ACE inhibitors as well, this report was published at the end of the interval studied and influenced our data minimally. By 1993, the JNC had moved closer to its earlier positions by reinforcing the utility of thiazide and ß-blocker therapy as first-line pharmacological approaches to high blood pressure.14 52

We found a substantial rise in the use of CCBs and ACE inhibitors in the treatment of hypertension during the 1980s, with a fourfold increase in the use of CCBs over the time interval studied. While the cost of medications had not previously played a major role in the development of guidelines for antihypertensive therapy, the JNC did address this issue for the first time in its 1988 report7 and echoed these statements in the 1993 report as well.14 The cost of therapy may be a barrier to controlling hypertension for both the patient and society. Two surveys found that approximately 25% of patients reported problems in paying for medications to treat their high blood pressure.53 54 The Rand Health Insurance Study found that hypertension was one of only two conditions for which a difference was found in health outcomes between patients receiving free care and those who paid out-of-pocket.55 56 The rapidly increasing use of newer and more expensive drugs such as CCBs and ACE inhibitors documented in our data are likely to increase substantially the cost of care of the hypertensive patient.22 57 This may paradoxically worsen outcomes for patients prescribed more expensive agents that they cannot afford, leading to poorer blood pressure control and increasing the incidence of hypertension-related sequelae.

Is the increased cost of the newer antihypertensive agents balanced by a greater therapeutic effect and decreased adverse drug reaction profile? One study addressed this issue by modeling the long-term cost-effectiveness of various antihypertensive regimens in a younger population with diastolic pressure greater than 95 mm Hg.58 This study assumed beneficial effects in morbidity and mortality of the newer antihypertensive agents that were equal to those of thiazide diuretics and ß-adrenergic blockers, although the data to support this do not exist. Over a projected 20-year interval, propranolol and hydrochlorothiazide were estimated to be the most cost-effective regimens, with other drugs (eg, captopril) costing up to 74 times more per year of life saved. Several major investigations on the treatment of mild hypertension showed no important differences in blood pressure control, side effects, or quality of life,18 59 60 61 although other trials have come to different conclusions.62 63 64 While it is the goal of the clinician to encourage compliance with the therapeutic regimen, limited income as well as restricted health insurance benefits make it hard for elderly patients to acquire prescribed medications.51 Since there is no evidence that the newer agents result in improved health outcomes, the increased costs associated with their widespread use cannot be justified on a population-wide basis.

Certain caveats must be considered in interpreting the present study findings. Because of the potential incompleteness of outpatient diagnostic clinical information in Medicaid files, we could not be certain of the diagnosis of hypertension in all subjects. Several antihypertensive drugs have other indications, and prescriptions for these agents may not all represent treatment of hypertension.24 However, when we repeated the analyses excluding subjects with evidence of other cardiovascular medication use or diagnoses, we found very similar trends in diuretic use and factors associated with the prescribing of this drug class. In addition, the 1982 to 1988 period represented an era during which thiazides and ß-blockers were used primarily for the management of high blood pressure; CCBs and ACE inhibitors were first introduced as antihypertensive agents and only later (ie, in the late 1980s and beyond) was their use extended to other cardiovascular diagnoses.

Because subjects' medical histories before 1981 or before Medicaid eligibility were unknown, some cohort members could have had instances of remote antihypertensive use that were not evident. Nonetheless, even if these subjects used antihypertensive drugs previously, reinitiation of therapy would represent a significant clinical event that parallels initial therapy. Out-of-system use of antihypertensive medications would not have been captured in our database. However, this problem is very uncommon, because all medications are provided free of charge to these indigent individuals through the Medicaid program. Our earlier experience with these data for studies of medication use indicates that the methods outlined above represent a practical and efficient means for the investigation of such questions in very large populations.65 66 67 68 We were limited to studying strategies in the pharmacological therapy of hypertension in the elderly and were unable to document trends in the nonpharmacological management of this disorder. Applegate et al69 recently demonstrated that weight loss and sodium restriction were effective in lowering diastolic pressure in a sample of patients aged 60 to 85 years.

Since we did not have denominator data on the base population of elderly Medicaid patients over time, we reported frequencies rather than rates of antihypertensive use and thus did not estimate incidence rates of antihypertensive use in this population. Nonetheless, our data are representative of typical prescribing patterns in the elderly; prescribing reimbursement through Medicaid tends to reflect physicians' prescribing for patients in their practice as a whole. Continuous monitoring of an entire population allowed us to identify all first prescriptions written for this very large group of "free-living" subjects.

Further studies are needed to validate these findings and to address prescribing influences affecting clinicians treating the elderly. In contradiction to growing concern about costs53 70 and the role of the scientific literature in influencing physician prescribing practices,71 72 73 74 trends in prescribing toward the more expensive CCBs and ACE inhibitors in the face of equal antihypertensive efficacy among agents present a concern relevant to policymakers, physicians, and patients alike.


*    Acknowledgments
 
This work was supported by a grant (AG08812) from the National Institute on Aging, Bethesda, Md, and by a Grant-in-Aid (94012980) from the American Heart Association, Massachusetts Affiliate. Dr Monane is a recipient of a Clinical Investigator Award (K08 AG00642) from the National Institute on Aging, as is Dr Gurwitz (K08 AG00510). The authors wish to thank Rita Bloom and Sharon Hawley for their assistance in the preparation of the manuscript.

Received November 30, 1994; first decision December 23, 1994; accepted January 26, 1995.


*    References
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *References
 

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