BRIEF OBSERVATIONS

Use of Cholesterol-lowering Medications inthe United States from1991 to 1997David Siegel, MD, MPH, Julio Lopez, PharmD,Joy Meier, PharmD

The benefits of cholesterol-lowering medication inhypercholesterolemic patients was first suggestedby the long-term follow-up of the Coronary Drug

Project, which studied the use of niacin in men with pre-vious myocardial infarction (1). Since that study, severalsecondary prevention trials using different 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)have found even greater benefit in these patients (2,3),including men and women with average serum choles-terol levels (4). Benefits have also been shown in a pri-mary prevention trial among men with hypercholesterol-emia (5). In 1988, the National Cholesterol EducationProgram (NCEP) issued recommendations for the detec-tion and control of hypercholesterolemia (6). Subse-quently, there has been increased use of cholesterol-low-ering medications (7,8), although several studies indicatethat these drugs are underutilized (9 –11).

Several investigators have studied the patterns of use ofcholesterol-lowering medications by geographic region,physician specialty, and type of health care insurance(9,11), and there have also been studies of adherence andadequacy of dosage (12–14). None of these reports eval-uated a national sample to determine whether the pat-terns of cholesterol-lowering therapy have changed withtime, in terms of class of medication or use of specificmedications. To provide information on these questions,we examined national trends in prescribing patterns forcholesterol-lowering medications from 1991 through1997.

METHODS

US retail prescription data were obtained from Scott-Levin, Inc, Newton, Pennsylvania. Data from about 2.3billion prescriptions per year (about 70% of all prescrip-tions dispensed by retail pharmacies), dispensed by al-most 35,000 retail pharmacies representing all 50 states,were used to project retail prescription sales (15,16). Re-tail pharmacies dispense approximately 68% of all phar-maceutical and diagnostic medications in the UnitedStates.

We obtained information about all brands and doses of

medications used to treat dyslipidemias for each calendaryear from 1991 through 1997, including the name of themedication (or its generic name if available from morethan one source), strength, estimated number of retailprescriptions, and total number of units dispensed. Foreach medication, data were aggregated for all doses andconsolidated by medication class (statin, bile-acid bind-ing resin, niacin, fibrate, and probucol). Treatment-yearsfor each medication class were estimated by dividingunits dispensed by daily frequency times 365. The cost ofone pill or tablet (unit price) was based on the averagewholesale price of medications (17) dispensed in lots ofeither 90 or 100 pills, depending upon manufacturerpreference. The annual cost per preparation was calcu-lated as the unit price multiplied by the estimated numberof units dispensed. Costs were aggregated for each medi-cation and for each class of medication, as well as for thetotal wholesale cost of cholesterol-lowering medicationsdispensed by retail pharmacies. We used 1997 prices tocompare costs by year.

RESULTS

The estimated total number of prescriptions (both newand refill) for cholesterol-lowering medications that weredispensed by US retail pharmacies increased from 22.5million in 1991 to 39.9 million in 1997 (Table 1). Thisrepresents an increase from 2.25 million treatment-yearsin 1991 to 5.46 million treatment-years in 1997. Therewas a steady increase in the use of statins as a proportionof cholesterol-lowering medication, from 47% in 1991 to78% by 1997, at which time they accounted for 4.72 mil-lion treatment-years. While the use of fibrates remainedapproximately the same, their use as a proportion of allcholesterol-lowering medications decreased from 27% in1991 to 11% in 1997. The use of bile-acid binding resinsdecreased both absolutely and as a proportion of pre-scribed cholesterol-lowering medications.

The patterns of use of statins changed after the intro-duction of new agents in this class (Table 2). In 1991,lovastatin was the only available statin, and it accountedfor 1.21 million treatment-years of prescriptions. Prava-statin was introduced in late 1991, simvastatin in 1992,fluvastatin in 1994, and atorvastatin in 1997. Simvastatinbecame the most frequently prescribed statin in retailpharmacies in 1996, a position it maintained in 1997,during which time its use accounted for 1.52 milliontreatment-years. During its introductory year in 1997,atorvastatin was the third most frequently prescribedmedication in this class, accounting for 0.75 million treat-ment-years.

In 1991, US pharmacies spent about $3.03 billion oncholesterol-lowering medications. This amount in-

496 q2000 by Excerpta Medica, Inc. 0002-9343/00/$–see front matterAll rights reserved. PII S0002-9343(00)00319-3

creased yearly, reaching $5.03 billion in 1997. During thisperiod, statins increased from 32% ($1.05 billion) to 78%($4.0 billion) of the total cost, while the amount thatpharmacies spent on bile-acid binding resins decreasedfrom $1.42 to $0.62 billion, and the amount spent onfibrates decreased from $0.52 to $0.41 billion. Also dur-ing this period, the amount spent on niacin decreasedfrom $9.6 to $2.2 million, and the amount spent on pro-bucol decreased from $32.1 million to only $34,000.

DISCUSSION

Changes in the use of cholesterol-lowering medicationsbetween 1991 and 1997 included both an absolute in-crease in the use of these agents, as well as a proportionateincrease in the use of statins. Despite the increased use ofcholesterol-lowering medications, there are millions ofpatients in the United States who should be receivingthese medications but are not. Retail pharmacies dis-pensed the equivalent of 5.46 million years of cholesterol-lowering medications in 1997. If 68% of prescriptionswere filled in retail pharmacies (18), and patients actuallytook 64% of prescribed statins and 37% to 60% of theother cholesterol-lowering medications (13), then ap-proximately 13 million people received prescriptions forthese agents in 1997. However, approximately 38 millionadults in the United States have serum total cholesterollevels of 240 mg/dL or greater, and 96 million have levelsgreater than 200 mg/dL. In addition, there are 13.9 mil-

lion patients with coronary artery disease (19 –21). Rec-ommendations from different expert organizations vary,but based on NCEP guidelines (22), many of these pa-tients should be treated with cholesterol-lowering medi-cations.

We observed a substantial increase in the use of statins,from 47% of cholesterol-lowering medications dispensedin 1991 to 78% in 1997. These trends antedated the pub-lication of the results from randomized trials that dem-onstrated their beneficial effects on morbidity and mor-tality from coronary artery disease, and may reflect theirbetter tolerability compared with niacin or bile-acidbinding resins (13). The types of statins changed after theintroduction of new agents, perhaps because of percep-tions that these newer medications had different effectson lipid levels. All statins, however, have a good dose-response curve for lowering low-density lipoprotein(LDL) cholesterol. Recent evidence indicates that an80-mg dose of atorvastatin, lovastatin, or simvastatinlowers LDL-cholesterol levels by approximately 50%(23,24). Thus, the switch from lovastatin to simvastatincannot be explained by differences in potency of the med-ications. Since the same pharmaceutical company mar-kets both drugs, changes in promotion practices to stressthe use of the newer agent may be responsible. Anotherpossible explanation is that simvastatin and atorvastatinare also approved by the Food and Drug Administrationfor the treatment of elevated triglyceride levels.

There are several limitations to our study. Our datawere based on prescriptions; we did not have clinical in-

Table 1. Patterns of Use of Cholesterol-lowering Medications, as Dispensed by US Retail Pharmacies from 1991 to 1997

Class of Medication

1991 1992 1993 1994 1995 1996 1997

Treatment-Years in Thousands (Percentage for That Year)

Statins 1,211 (53.8) 1,544 (62.2) 1,820 (67.6) 2,231 (71.7) 2,738 (75.8) 3,478 (80.2) 4,716 (86.3)Fibrates 620 (27.5) 609 (24.5) 592 (22.0) 622 (20.0) 635 (17.6) 640 (14.8) 576 (10.5)Bile-acid binding

resins284 (12.6) 231 (9.3) 202 (7.5) 194 (6.2) 186 (5.2) 180 (4.2) 145 (2.7)

Niacin 64 (2.8) 53 (2.1) 46 (1.7) 42 (1.3) 34 (0.9) 31 (0.7) 26 (0.5)Probucol 75 (3.3) 48 (1.9) 31 (1.2) 23 (0.7) 17 (0.5) 4 (0.1) 0 (0.0)Total 2,254 2,484 2,691 3,111 3,610 4,334 5,464

Table 2. Trends in Use of Statins from 1991 to 1997*

1991 1992 1993 1994 1995 1996 1997

Treatment-Years in Thousands (Percentage of Statin Use in That Year)

Simvastatin 84 (5.4) 250 (13.8) 432 (19.4) 704 (25.7) 1,166 (33.5) 1,520 (32.2)Pravastatin 2 (0.1) 168 (10.9) 366 (20.1) 521 (23.4) 605 (22.1) 789 (22.7) 1,049 (22.3)Atorvastin 754 (16.0)Lovastatin 1,210 (99.9) 1,292 (83.7) 1,203 (66.1) 1,178 (52.8) 1,062 (38.8) 951 (27.3) 738 (15.6)Fluvastatin 100 (4.5) 366 (13.4) 572 (16.5) 655 (13.9)All statins 1,211 1,544 1,820 2,231 2,738 3,478 4,716

* Based on prescriptions dispensed by US retail pharmacies.

Brief Observations

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formation about the treated patients. However, the med-ications that we studied are used almost exclusively forthe treatment of dyslipidemias; thus, our analysis of thepatterns of use should be valid. We did not have informa-tion about patterns of use of these medications in healthmaintenance organizations that do not use retail phar-macies. It will be of interest to compare the results ofother analyses of the patterns of use of cholesterol-lower-ing medications in other settings, and using other meth-ods such as chart review or provider surveys of prescrib-ing patterns, with our findings.

Another limitation is that we could not distinguishnew and refill prescriptions. This does not affect the ma-jor findings of the study, which are the overall increase inthe use of cholesterol-lowering medications, as well as thechange in the pattern of the classes of medications. Fi-nally, between 1991 and 1997 there was a small decrease(about 1%) in the proportion of medications dispensedby retail pharmacies, primarily due to an increase in med-ications dispensed by mail order pharmacies (25). Thischange would result in an underestimation of the in-crease in the use of cholesterol-lowering medications inour study.

While there remains considerable debate about who isan appropriate candidate for cholesterol-lowering medi-cation (26 –29), our results indicate that these medica-tions are underutilized, even based on the narrowest in-dications for use. As with the treatment of hypertension,for which national guidelines had little effect on prescrib-ing patterns of antihypertensive medications (16), greaterattention must be paid to educating health care providers,as well as to making system-wide changes, so that treat-ments of proven benefit are implemented.

REFERENCES1. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in

coronary drug project patients: long-term benefit with niacin.JACC. 1986;8:1245–1255.

2. Scandinavian Simvastatin Survival Study Group. Randomised trialof cholesterol lowering in 4444 patients with coronary heartdisease: the Scandinavian simvastatin survival study (4S). Lancet.1994;344:1383–1389.

3. Byington RP, Jukema JW, Jukka TS, et al. Reduction in cardiovas-cular events during pravastatin therapy. Circulation. 1995;92:2419 –2425.

4. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin oncoronary events after myocardial infarction in patients with averagecholesterol levels. NEJM. 1996;335:1001–1009.

5. Shepherd J, Cobbe ST, Ford I, et al. Prevention of coronary heartdisease with pravastatin in men with hypercholesterolemia. NEJM.1995;333:1301–1307.

6. Expert Panel on Detection, Evaluation, and Treatment of HighBlood Cholesterol in Adults. Report of the National CholesterolEducation Program Expert Panel on Detection, Evaluation, andTreatment of High Blood Cholesterol in Adults. Arch Intern Med.1988;148:36 – 69.

7. Nieto FJ, Alonso J, Chambless LE, et al. Populations awareness and

control of hypertension and hypercholesterolemia. Arch InternMed. 1995;155:677– 684.

8. Pieper RM, Arnett DK, McGovern PG, et al. Trends in cholesterolknowledge and screening and hypercholesterolemia awareness andtreatment, 1980 –1992. Arch Intern Med.1997;157:2326 –2332.

9. Stafford RS, Blumenthal D, Pasternak RC. Variations in cholesterolmanagement practices of U.S. physicians. JACC. 1997;29:139 –146.

10. Lemaitre RN, Furberg CD, Newman AB, et al. Time trends in theuse of cholesterol-lowering agents in older adults. Arch Intern Med.1998;158:1761–1768.

11. McBride P, Schrott HG, Plane MB, et al. Primary care practiceadherence to national cholesterol education program guidelines forpatients with coronary heart disease. Arch Intern Med. 1998;158:1238 –1244.

12. Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation ofantihyperlipidemic drugs. Do rates reported in clinical trials reflectrates in primary care settings? NEJM. 1995;332:1125–1131.

13. Avorn J, Monette J, Lacour A, et al. Persistence of use of lipid-lowering medications. JAMA. 1998;279:1458 –1462.

14. Marcelino JJ, Feingold KR. Inadequate treatment with HMG-Co Areductase inhibitors by health care providers. Am J Med. 1996;100:605– 610.

15. The top 200 drugs. Am Drug. 1998;215:46 –53.16. Siegel D, Lopez J. Trends in antihypertensive drug use in the United

States. JAMA. 1997;278:1745–1748.17. 1997 Drug Topics Redbook. Montvale, NJ: Medical Economics;

1997.18. Hough J. IMS hospital pharmacy review: leading dollar volume

pharmaceuticals. Hosp Pharm. 1998;1997:33:498 –522.19. American Heart Association. Heart and Stroke Facts, 1994 Statistical

Supplement. Dallas: Am Heart Assocation; 1994.20. Gartside PS, Glueck CJ. Relationship of dietary intake to hospital

admission for coronary heart and vascular disease: the NHANES IInational probability study. J Am Col Nutr. 1993;12:676 – 684.

21. Gartside PS, Glueck CJ. The important role of modifiable dietaryand behavioral characteristics in the causation and prevention ofcoronary heart disease hospitalizations and mortality: the prospec-tive NHANES I follow-up study. J Am Col Nutr. 1995;14:71–79.

22. Expert Panel on Detection, Evaluation, and Treatment of HighBlood Cholesterol in Adults. Summary of the second report of theNational Cholesterol Education Program (NCEP) Expert Panel ondetection, evaluation, and treatment of high blood cholesterol inadults (Adult Treatment Panel II). JAMA. 1993;269:3015–3023.

23. Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol.1997;79:38 – 42.

24. Jones P, Kafonek S, Hunninghake D. Comparison dose efficacystudy of atorvastatin, versus simvastatin, pravastatin, lovastatin,and fluvastatin in patients with hypercholesterolemia (theCURVES study). Am J Cardiol. 1998;81:582–587.

25. 1998 Industry Profile and Healthcare Factbook. Reston, Vir: NationalWholesale Druggists’ Association; 1998:109.

26. Garber AM, Browner WS, Hulley SB. Cholesterol screening inasymptomatic adults, revisited. Ann Intern Med. 1996;124:518–531.

27. LaRosa JC. Cholesterol agonistics. Ann Intern Med. 1996;124:505–508.

28. Forrester JS, Sha PK. Using serum cholesterol as a screening test forpreventing coronary heart disease: the five fundamental flaws of theAmerican College of Physicians guidelines. Am J Cardiol. 1997;79:790 –792.

29. Grundy SM, Balady GJ, Criqui MH, et al. When to start cholesterol-lowering therapy in patients with coronary heart disease: a state-ment for healthcare professionals from the American Heart Asso-ciation task force on risk reduction. Circulation. 1997;95:1683–1685.

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498 April 15, 2000 THE AMERICAN JOURNAL OF MEDICINEt Volume 108

From the Medical Service (DS), Department of Veterans Affairs, NorthernCalifornia Health Care System, Mather, California; the Center for HealthServices Research in Primary Care and Department of Medicine (DS),University of California, Davis; the Pharmacy Service (JL, JM), Depart-ment of Veterans Affairs, Northern California Health Care System, Mar-tinez, California; and the School of Pharmacy (JL, JM), University of thePacific, Stockton, California.

The views expressed in this paper do not necessarily represent the views ofthe Department of Veterans Affairs or of the United States Government.

Correspondence should be addressed to David Siegel, MD, Chief, Med-ical Service (111), Department of Veterans Affairs NCHCS, 10535 Hospi-tal Way, Mather, California 95655.

Manuscript submitted August 20, 1999, and accepted in revised formDecember 28, 1999.

Effective Teaching forPreceptors of AmbulatoryCare: A Survey ofMedical StudentsWalter N. Kernan, MD, Mary Y. Lee, MD,Sarah L. Stone, MD, Kimberly A. Freudigman, PhD,Patrick G. O’Connor, MD

Faculty development has emerged as a major strat-egy for optimizing the quality of instruction in pre-doctoral ambulatory care training in internal med-

icine. The appropriate curriculum for faculty develop-ment, however, is uncertain because research has notadequately identified effective teaching behaviors for thissetting (1). Based on the theory that students are a validsource of ideas for educational strategy, we conducted asurvey among experienced medical students to ascertaintheir opinions on effective teaching behaviors.

MATERIAL AND METHODS

At Yale and Tufts Universities, we convened nine focusgroups of third-year medical students who had com-pleted 1-month rotations in ambulatory care internalmedicine (2). Students were asked to identify teachingbehaviors that facilitated their learning; from transcriptsof these sessions, we identified 94 such behaviors, whichwere divided into seven domains of teaching by the con-sensus of the investigators. The 94 behaviors were used toconstruct a survey that was administered to students whohad completed 1-month internal medicine ambulatoryrotations at Yale, Tufts, and the University of Massachu-setts. For each behavior, students were asked two ques-tions. The first was, “Do you recommend preceptors usethe behavior?” The five response options were “yes,strongly,” “yes, somewhat,” “not sure,” “no, somewhat,”and “no, strongly.” The second was “How important isthe behavior to your learning?” The five response options

were “extremely important,” “very important,” “some-what important,” “not very important,” and “not at allimportant.”

For each behavior, we calculated the percentage of stu-dents who recommended it “strongly” or “somewhat”and rated it “extremely” or “very” important. We defineda behavior as “effective” and “valued” if the percentagewas $75%, “possibly valued” for 25% to 74%, and “notvalued” for ,25%.

RESULTS

Of the 150 students who volunteered to complete thesurvey, 122 (81%) returned it. Their mean (6 SD) agewas 26 6 3 years. Fifty-six percent were female and 26%were minority (African-American [5%], Hispanic [3%],or Asian/Pacific Islander [18%]).

Among the 94 teaching behaviors listed in the survey,51 met our criteria for being considered as effective (Ta-ble 1). More than half involved teaching clinical skills andknowledge. Teaching clinical skills included many behav-iors that preceptors can use to maintain a student’s inde-pendent involvement in patient care. They also reflectstudents’ desire to practice skills they are attempting tomaster. These behaviors include assuring that the studentsees and examines patients alone, asking for the student’sassessment and plan before giving one’s own, delegatingresponsibility to the student for the wrap-up discussionwith the patient, and delegating responsibility to the stu-dent for ascertaining and interpreting test results. Otherbehaviors related to teaching clinical skills involve en-couraging students to reason with clinical information.Students recommended that preceptors guide students indevising a plan of care, ask questions to lead students totheir own diagnosis or treatment, and challenge studentsto explain their choices. Students also recommended thatpreceptors observe students’ techniques of physical ex-amination and demonstrate findings on patients whomstudents may not be caring for. A common complaintduring focus groups was that preceptors did not teachphysical diagnosis.

Within the domain of teaching knowledge, there werefive recommended behaviors about asking questions.These include questioning to probe a student’s knowl-edge and to improve a student’s understanding of partic-ular issues, and asking questions that focus on importantmatters rather than trivia. Two other behaviors includedexplaining the science and pathophysiology behind diag-noses and procedures, and explaining therapeuticchoices. Preceptors were encouraged not to assume thestudent knows too much.

Several recommended behaviors involved the timingof feedback. Students wanted preceptors to give feedbackpromptly during or after patient visits, before students

Brief Observations

April 15, 2000 THE AMERICAN JOURNAL OF MEDICINEt Volume 108 499