J. Jaime Caro, MD, and Karen Lee, MA

Atenolol Versus Captopril in Patients with Type 2 Diabetes

Gray A, Clarke P, Adlert A, et al.: An economic evalua-tion of atenolol vs. captopril in patients with type 2 diabetes (UKPDS 24). Diabetic Med 2001,18:438–444.

Rating: •Of importance.

Introduction: Although the effectiveness and the costs ofcaptopril and atenolol have been published, this is the firstdirect economic comparison of the two.

Aims: To compare the net direct costs from a health carepurchaser’s perspective of implementing a tight bloodpressure control policy (< 150/< 80 mm Hg) with captoprilor atenolol in patients with type 2 diabetes.

Methods: This study randomly allocated 758 hypertensivepatients from the United Kingdom Prospective Diabetes Studyto either captopril or atenolol. Resource use data on medica-tion doses and hospital admissions were obtained at each visit,and information on all outpatient health care was obtainedonce and used to develop a predictive model that was thenapplied to estimate outpatient resource use over the entire trial.Costs (in 1997 pounds sterling) were obtained from the cen-ters, trusts, and other local sources. Survival was derived using amodel assuming identical hazards beyond the trial.

Results: Only the costs of hospitalizations differed, lead-ing to a savings of about 1000 pounds per patient withatenolol. As expected given the methods, there was no esti-mated difference in survival.

Discussion: The study provides evidence for the use ofatenolol on a cost basis over captopril. Sensitivity anal-ysis showed that even drastic reductions in captoprilprice would not alter the results. Potential explanationsfor the reduction in hospitalizations with atenololwere discussed.

Editor’s comments

The strengths of this study are the randomized allocationand the actual collection of resource use data; the mainweakness is the unspecified amounts of missing data.Although there was no difference in the predeterminedhealth outcomes, the difference in hospitalizations pointsto an effectiveness disparity, which will require further elu-cidation. The resulting economic advantage seems compel-ling, but atenolol’s adverse effect of glycemic control couldhave longer term harmful consequences. The extrapolationof survival in this study was superfluous.

Efficacy and Safety of a Therapeutic Interchange from High-dose Calcium Channel Blockers to a Fixed-dose Combination of Amlodipine/Benazepril

Hilleman DE, Reyes AP, Wurdeman RL, Faulkner M: Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. J Hum Hypertens 2001, 15:559–565.

Rating: •Of importance.

Introduction: Reduction of higher blood pressure lev-els often requires high-dose monotherapy or combina-

tion treatment, and a fixed-dose combination may bean attractive alternative.

Aims: To evaluate the efficacy, safety, and cost ofswitching from a high-dose calcium channel blockertherapy (amlodipine, felodipine, or nifedipine-GITS)to a fixed dose combination of amlodipine andbenazepril in patients with controlled hypertension.

Methods: Seventy-five patients were switched withouttapering to combination therapy and followed for 1

418 Antihypertensive Therapy: Compliance, Quality of Life, and Pharmacoeconomics

year. All direct costs in US dollars (year 2000 implied)were assessed following the switch. The study imposedseveral (unclear how many) visits.

Results: The majority of patients, 88%, were success-fully switched, with fewer side effects than had beenexperienced with calcium channel blockers, and overallsavings of $214 because of lower drug price (those orig-inally on felodipine incurred a cost of $26).

Discussion: The study confirms that switching to a lowerpriced fixed-dose combination brings savings. The short-comings of the study (not blinded, retrospective collection

of calcium channel blocker data, lack of a washout period)were mentioned but not discussed.

Editor’s comments

The results of this study are not surprising, since drug price isoften the strongest determinant of net cost. The savings areprobably an underestimate because all the resource use subse-quent to the switch was counted, but none counted before-hand. Some savings may be generated by the switch, but not allof it. Neither funding of the study nor compliance with ethicalprecepts were mentioned.

Pharmacoeconomic Evaluation of a Pharmacist-managed Hypertension Clinic

Okamoto MP, Nakahiro RK: Pharmacoeconomic evaluation of a pharmacist-managed hypertension clinic. Pharmacotherapy 2001, 21:1337–1344.

Rating: •Of importance.

Introduction: Although intervention by a pharmacist hasbeen shown to improve outcomes in hypertension man-agement, its cost effectiveness has not been assessed.

Aims: To compare clinical, economic, and “humanistic”outcomes in a pharmacist-managed hypertension clinicwith those in a physician-managed clinic.

Methods: Three hundred–thirty adult patients receivingdrugs for essential hypertension were randomized to eithermanagement of hypertension drug therapy by a pharmacistor to continue routine physician management. Blood pres-sure and health status scores (Short Form 36) wereobtained at baseline and 6 months, while data on healthcare resources used (emergency room visits, hospitaliza-tions, clinic visits) were obtained retrospectively at 6months. Costs were obtained directly from the managedcare organization in 1998 US dollars.

Results: Blood pressure decreased significantly in thepharmacist-managed patients but not in those continuingphysician care, and the difference was statistically signifi-cant. In addition, the quality of life of pharmacist-man-

aged patients improved while it decreased in physiciancare. Drug costs and emergency department visit frequencywere lower but clinic visit costs were higher in pharmacist-managed patients, leading to no significant cost difference.Incremental cost-effectiveness ratios of $1.18/mm Hgreduction in systolic blood pressure and $2.52/mm Hg indiastolic blood pressure were obtained.

Discussion: The study demonstrated that pharmacistscan produce better blood pressure control with littleimpact on costs. The inability to lower costs was due to thegreater number of visits. The authors acknowledged somelimitations (not focusing on newly diagnosed patients,inclusion of only the more expensive antihypertensives,attribution of costs to hypertension).

Editor’s comments

This is a very well conducted and reported study indicatingthat pharmacist management of chronic drug therapy mayyield better results, though somewhat surprisingly, notlower costs. The authors minimize the quality-of-life effectsbut the numbers are favorable. The cost-effectivenessratios, however, are rather meaningless as they are quotedin terms of mm Hg reductions rather than a more telling“success” (mean blood pressures just don’t say much). Alarge proportion of patients were either not deemed eligi-ble for or did not participate in the study.

Clinical Trials Report 419

Pharmacoutilization of Antihypertensive Drugs

Degli Esposti E, Sturant A, Degli Esposti L, et al.: Pharmacoutilization of antihypertensive drugs: a model of analysis. Int J Clin Pharmacol Ther 2001, 39:251–258.

Rating: •Of importance.

Introduction: The importance of compliance with antihy-pertensive medications, and its failings in actual practice, havebeen recognized.

Aims: To identify indicators of adherence using an auto-mated dispensing database.

Methods: A retrospective analysis was conducted ondispensing data from 1997 (and possibly 1998) fromRavenna, Italy. Patients receiving amlodipine, atenolol,fosinopril, indapamide, or losartan for the first timewere included and classified as discontinuers, continu-ers, or switchers based on their dispensing pattern. Thedirect costs in 1998 Italian Lira were calculated basedon local market prices.

Results: Two thirds of patients discontinued treatment andanother 10% switched. After a steep early drop, there was aslow deterioration in compliance, with losartan significantlybetter than the rest. The cost of treatment was significantlylower for those starting on indapamide or atenolol.

Discussion: The study evaluated the behavior of patientsstarting antihypertensive treatment with one of five drugs repre-senting the major classes. Compliance was shown to be verypoor. The analyses demonstrate the possibility of using auto-mated databases to study compliance.

Editor’s comments

The study replicates work done by others in this area and con-firms that compliance with antihypertensive drugs is poor. It isinteresting to see that the angiotensin II receptor antagonistperforms better, as predicted in earlier studies. The costsincluded solely those of the drugs, an important lapse becausethere can be significant costs associated with monitoring andswitching medications (eg, physician or clinic visits).