Pharmacoeconomic Issues inAntihypertensive Therapy

Thomas D. Giles, MD

Today’s healthcare environment is one of perpetualchange, increasing costs, and scarce resources. Healthcareprofessionals, insurers, and consumers are constantly chal-lenged with balancing healthcare costs and quality of life.With so many antihypertensive agents to choose from,therapies that provide benefits beyond the decreasing ofblood pressure, will become the preferred therapies. How-ever, these agents must also demonstrate a desirable side-effect profile; agents that are effective but not complied

with will neither reduce costs nor improve quality of life.Angiotensin II receptor antagonists have the most favor-able adverse event profile of the antihypertensive agents.These drugs may become the preferred agents of physi-cians who factor indirect costs—less morbidity and greaterproductivity—into their selection of an antihypertensivetherapy. Q1999 by Excerpta Medica, Inc.

Am J Cardiol 1999;84:25K–28K

Adebate over cost versus quality of healthcare ser-vices arises in almost any discussion of treatment

options. Issues such as increasing healthcare costs,limitations of healthcare resources, and the tendencyof managed care organizations to pass financial risk onto others—especially point-of-service physicians—enter into the discussion of pharmacoeconomics.

In 1996, healthcare expenditures accounted for14.2% of the gross domestic product in the UnitedStates, and this percentage is expected to increase.1,2

Scrutiny of all aspects of healthcare, from physicians’salaries to the increasing cost of prescription drugs,require physicians to balance cost-effectivenessagainst quality of life.

ANALYZING COST CONSEQUENCESMany economic models have been developed to

measure cost consequences of the healthcare system.The traditional cost–benefit analysis model includes areview of costs versus outcomes determined in dollarresults (Figure 1). However, the cost–benefit analysismodel does not adequately reflect clinical outcomes(i.e., the effect on the patient).

To add clinical measures to the equation, the cost-effectiveness analysis model was introduced. Thismodel reviews costs versus outcomes defined by clin-ical measures, such as blood pressure reduction. Morerecently, economists have attempted to show the re-lation between costs and effects of illness or treatmenton quality of life by using the cost–utility analysismodel, which is illustrated by the following equation:

Net Costs

Net BenefitsO¡

Dollars

Value

The objective of the cost–utility analysis model is todetermine the impact of total health resource utiliza-tion on costs, measuring outcomes in terms of patientyears adjusted for quality of life (quality-adjusted lifeyears). Clinical, economic, and humane attributes,such as pain and suffering, are factored into the equa-tion for a more “real world” evaluation of the effectsof healthcare intervention.3,4

Quality-adjusted life years are subjective. For ex-ample, they take into account the difference in qualityof life for a person who lives fewer years but has nohealth problems versus a person who lives more yearswhile restricted by serious health problems.

Before the cost–utility analysis model can be usedeffectively, physicians must know the cost of thera-pies and their likely clinical outcomes. Figure 2 illus-trates a method of weighing economic results againstclinical results. The most desirable scenario is the bestclinical outcome at the lowest cost.

COSTS ASSOCIATED WITHHYPERTENSION

The costs of treating cardiovascular diseases havecontinued to increase, resulting in scrutiny of costsversus outcomes. The estimated costs associated withcardiovascular diseases are very high (Figure 3).5

Hospital costs comprise the largest portion of healthexpenditures, followed by frictional losses, such asloss of productive years due to illness or death. Med-ication costs comprise the smallest portion of totaltreatment costs for cardiovascular disease. However,the total cost of hypertension treatment in 1998 wasestimated at $23.3 billion, $7.5 billion of which werepharmaceutical costs.6 The cost of hypertension med-ication is high compared with the medication costs forall cardiovascular diseases.

Despite the amount of money spent to treat hyper-tension, and the availability of many antihypertensiveagents, less than one third of hypertensive adults havetheir blood pressure under adequate control. Accord-ing to phase II of the US National Health and Nutri-tion Examination Survey (NHANES) III (1991–1994),

From the Department of Medicine, Louisiana State University School ofMedicine, New Orleans, Louisiana.

Address for reprints: Thomas D. Giles, MD, Department of Medi-cine, Section of Cardiology No. 331E, Louisiana State UniversitySchool of Medicine, 1542 Tulane Ave, New Orleans, Louisiana70112.

25K©1999 by Excerpta Medica, Inc. 0002-9149/99/$20.00All rights reserved. PII S0002-9149(99)00363-X

awareness of high blood pressure among adults in-creased from 51% in 1976 to 68.4% in 1991. Inaddition, the percentage of patients being treated forhypertension increased from 31% in 1976 to 53.6% in1991. However, actual control of blood pressure inthis same population was 10% in 1976 and only27.4% in 1991.7

APPLYING ECONOMIC MODELS TOANTIHYPERTENSIVE TREATMENT

The economics of hypertension have not been stud-ied extensively because its effects on patients arevariable. Also, the costs related to hypertension, un-like other cardiovascular diseases such as heart fail-ure, are difficult to capture. However, there are exten-

FIGURE 2. Possible results of a study of clinical outcome versus cost.

FIGURE 3. Estimated costs of cardiovascular diseases in the United States as of 1985, showingmedication costs as the smallest portion of total costs. (Adapted with permission from J Hyper-tens Control.5)

FIGURE 1. Types of economic analyses showing costs versus outcomes in dollars and in clinicalmeasures.

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sive data describing the positive effects of controllinghypertension on morbidity and mortality.8,9 Thesepositive outcomes of controlling hypertension alsoproduce economic benefit.

Hypertension is an asymptomatic disease. There-fore, an asymptomatic patient with hypertension whois treated with an antihypertensive agent that causesside effects may perceive a lower quality of life,although blood pressure is controlled. Unfortunately,this scenario contributes substantially to patient non-compliance. Noncompliance, in turn, results in re-bound hypertension and potentially serious cardiovascu-

lar and renal complications. There are costs, then, asso-ciated with the side effects of hypertension medicationand resulting noncompliance with therapeutic regimens.

Ideally, physicians should prescribe medicationsthat effectively lower hypertension and enhance theirpatients’ quality of life. The physician must considernot only the cost of a drug but also the drug’s side-effect profile and the costs associated with treatingthose side effects. In essence, the physician must rely onoutcomes data, as illustrated in the formula in Figure 4,in an attempt to prevent morbid outcomes such as cere-brovascular, cardiovascular, and renal diseases.

FIGURE 4. Value of hypertension treatment: a balance between net costs and net benefits.

FIGURE 5. Telmisartan safety profile: comparison with placebo.

A SYMPOSIUM: ANGIOTENSIN II RECEPTOR ANTAGONISTS 27K

EFFICACY AND SIDE EFFECTS OFANTIHYPERTENSIVES

An extensive literature search shows that efficacyis similar for calcium antagonists,b blockers, angio-tensin-converting enzyme inhibitors, and angiotensinII receptor antagonists. However, each class of anti-hypertensive agents has a different side-effect profile.Common side effects of antihypertensive agents in-clude headache, dizziness, edema, palpitations, cough,and bronchitis. Calcium antagonists are associatedwith a substantially higher frequency of headache,edema, and palpitations, whereas angiotensin-convert-ing enzyme inhibitors are associated with cough,bronchitis, and dermatologic events.

Of all the available antihypertensive agents, angio-tensin II receptor antagonists have the most favorableadverse event profile. Figure 5 compares side effectsof the angiotensin II receptor antagonist, telmisartan,versus placebo.10 However, there is anecdotal evi-dence that the angiotensin II receptor antagonists areassociated with an increased incidence of urinary tractinfection and low back pain.

The direct costs of diuretics,b blockers, and cal-cium antagonists are comparable, whereas angioten-sin-converting enzyme inhibitors are significantlymore costly; the direct costs of angiotensin II receptorantagonists have not been studied. Nevertheless, itmay be the indirect costs associated with a drug—lessmorbidity and greater productivity due to better side-effect profiles—that should be considered when se-lecting antihypertensive therapy.

CONCLUSIONSWhether or not a treatment is cost-effective de-

pends on the perspective of those involved in treat-ment decisions, such as healthcare providers, patients,employers, insurers, and the government. These per-spectives can be based on very different factors and

may even conflict with one another. Physicians areadvised to understand the costs and quality-of-lifeissues necessary to make cost-effective treatment de-cisions while finding the best outcome for patients.Factors may include (1) new treatment versus tradi-tional, standard treatment; (2) monotherapy versuscombination therapy; or (3) diet adjustment versuspharmacologic intervention, to list a few examples.Although any treatment or intervention option costsmoney, using cost-containment strategies alone maylead to adverse outcomes.

Early identification and adequate treatment of pa-tients with hypertension produces measurable benefitsby reducing morbidity and mortality, and improvingthe quality of life. Factoring pharmacoeconomic is-sues into treatment options should result in a betterquality of life for patients.

1. Prescription drugs in the health care system. In: Industry Profile 1998,Executive Summary. PhRMA Publications [serial online]. Available at http://phrma.org/publications/industry/profile98. Accessed March 31, 1999.2. Browning SM. Forces for reforming the US health care system: a review of thecost and access issues.Health Econ1992;1:169–180.3. Jolicoeur LM, Jones-Grizzle AJ, Boyer JG. Guidelines for performing apharmacoeconomic analysis.Am J Hosp Pharm1992;49:1741–1747.4. Reeder CE. Overview of pharmacoeconomics and pharmaceutical outcomesevaluations.Am J Health Syst Pharm1995;52:S5–S8.5. Teeling Smith G. Health economics in hypertension control.J HypertensControl 1992;2:2–4.6. American Heart Association. 1998 Heart and Stroke Statistical Update. Dallas,TX: American Heart Association, 1997.7. Burt VL, Culter JA, Higgins M, Horan MJ, Labarthe D, Whelton P, Brown C,Roccella EJ. Trends in the prevalence, awareness, treatment, and control ofhypertension in the adult US population: data from the health examinationsurveys, 1960 to 1991.Hypertension1995;26:60–69.8. Moye LA, Davis BR, Hawkins CM, Probstfield JL. Conclusions and implica-tions of the Systolic Hypertension in the Elderly program.Clin Exp Hypertens1993;15:911–924.9. Medical Research Council trial of treatment of hypertension in older adults:principal results: MRC Working Party.BMJ 1992:304:405–412.10. Micardis Product Monograph 1999; Boehringer Ingelheim PharmaceuticalsInc., Ridgefield, CT.

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