lipid-lowering interventions in managed care settings

Lipid-lowering Interventions in Managed CareSettings

Joseph Fox, MD, Kenneth Jones, MD

Effective screening, treatment, and follow-up of pa-tients with elevated serum lipid levels is importantbecause of the very strong association between thiscondition and coronary heart disease (CHD). Screen-ing of patients with and without CHD for hyperlipid-emia is not generally carried out properly by man-aged care organizations (MCOs) or in other settings.Primary and secondary prevention are inadequate inmost patients with this condition; even in patientswho are treated, lipid-lowering therapy is often notused to its full potential. These trends have beenconfirmed by findings in the first of a three-phasehyperlipidemia outcomes management program car-ried out at 27 US MCOs. The efficacy of lipid-lower-ing therapy can be enhanced by physician educationand comprehensive, integrated quality improvementprograms. The cost-effectiveness of such treatmentcan be improved by individualizing both drug anddose to achieve National Cholesterol Education Pro-gram goals at the lowest drug acquisition cost. Thequality improvement program described and otherslike it have the potential to reduce the morbidity andmortality associated with CHD while decreasing thehuge economic burden associated with this disease.Several such programs have been undertaken atMCOs, some with more success than others. Inter-ventions and assessments of the type planned inphases 2 and 3 of this program can help to reducethe cost of lipid-lowering therapy without compro-mising cholesterol goal achievement. Am J Med.2001;110(6A):24S–30S. © 2001 by Excerpta Medica,Inc.

Athree-phase hyperlipidemia outcomes manage-ment program that has been described in earlierarticles of this supplement1,2 is being carried out

at 27 US MCOs. The findings from phase 1 (see Latts2)provide encouragement about the effectiveness of lipid-lowering therapy in the managed care setting, but theyalso show areas in need of improvement; these will beaddressed in the subsequent phases of the study. Onesuch area requiring significant improvement is docu-mentation of the effects of antihyperlipidemic treatment.The program enrolled and obtained sociodemographicdata on 7,619 patients, including 3,018 with CHD. How-ever, follow-up information about lipid levels after ther-apy was started was recorded for only 6,045 (79%) ofthese patients. Thus, .1 in 5 patients were not being ef-fectively followed up after the initiation of therapy. Fur-thermore, only 46% of patients had both baseline andfollow-up data on file. This is an important deficiency inthe management of patients with hypercholesterolemia.

A more positive finding was that lipid-lowering ther-apy with statins was effective in meeting National Cho-lesterol Education Program (NCEP) targets for low-den-sity lipoprotein cholesterol (LDL-C) in a relatively largefraction of patients. On-treatment LDL-C levels for the79% of enrolled patients who were observed indicatedthat 64% achieved their NCEP targets for LDL-C. Thus,nearly two thirds of patients treated and observed canexpect a significant reduction in cardiovascular risk.3

Another important finding of phase 1 was that the per-centage of patients achieving their NCEP-defined goalsdecreased as the target became more stringent. Targetswere reached by 87% of patients whose goal was forLDL-C levels to be ,160 mg/dL (those without CHD andwith less than two NCEP risk factors), 65% of those witha goal of ,130 mg/dL (no CHD but at least two riskfactors), and only 44% of those with a goal #100 mg/dL(those with CHD present). This pattern of increasing goalattainment with higher LDL-C target levels also occurredin the Lipid Treatment Assessment Project (L-TAP). Inthat study, however, the percentages of patients achievingthe goals of 160, 130, and 100 mg/dL with lipid-loweringtherapy were, respectively, 68%, 37%, and 18% (Figure1), lower than those in our study.4

Phase 1 results also indicated a substantial negative re-lation between the percent reduction in LDL-C requiredto achieve goal and the number of patients reaching tar-gets. Overall, 66% of patients who met their treatment

From M-Plan, Indianapolis, Indiana, USA (JF), and University of Flor-ida, Jacksonville, Florida, USA (KJ).

Requests for reprints should be addressed to Joseph Fox, MD, M-Plan, 8802 N Meridian Street, Indianapolis, Indiana 46260.

24S © 2001 by Excerpta Medica, Inc. 0002-9343/01/$20.00All rights reserved. PII S0002-9343(01)00675-1

goals required no more than a 25% reduction in LDL-C.This was true for only 24% of those who did not achievetheir targets. In contrast, only 8% of the patients whoachieved their goals required more than a 40% reductionin LDL-C. This was the case for 36% of patients who didnot achieve their targets.

Phase 1 further showed that statins are probably notbeing used as cost-effectively as possible by prescribers inthe participating health plans. The results of several phar-macoeconomic studies have indicated that fluvastatinmay be the most cost-effective drug in its class for man-agement of patients requiring modest (,30%) reduc-tions in LDL-C to meet their NCEP treatment goals.5–7

These findings are generally consistent with the phase 1results, which showed that the percentage reduction inLDL-C achieved with the lowest dose of fluvastatin (20mg/day) was very similar to those obtained with all dosesof all other statins, with the exception of high doses ofatorvastatin and simvastatin.

A key objective of phase 2 of this hyperlipidemia out-comes management program is to develop and imple-ment educational interventions that will address the de-ficiencies described above in patient follow-up and druguse. Previous attempts by MCOs and other groups toidentify candidates for lipid-lowering therapy, treatthem, and observe them during therapy have had variablesuccess.

ISSUES IN HYPERLIPIDEMIATREATMENT

Identifying Patients Who Will Benefit fromTreatmentThe first step in the effective management of patients withhyperlipidemia is identification of these individuals.However, current screening for both primary and sec-ondary prevention by MCOs generally falls far short ofthe NCEP recommendations of measurement of total se-rum cholesterol and high-density lipoprotein cholesterol(HDL-C) once every 5 years in adults .20 years old.3

In the realm of primary prevention, one recent surveyof 1,200 MCOs by Amonkar et al8 indicates that choles-terol screening is very limited (Table 1). Almost no pa-tients ,30 or .70 years of age underwent routine cho-

Figure 1. Patients reaching National Cholesterol Education Program (NCEP) treatment goals in the hyperlipidemia outcomesmanagement program versus in the Lipid Treatment Assessment Project (L-TAP).4

Table 1. Cholesterol Screening Among Adults Aged 18 to 69in a Typical Managed Care Organization

Age (yr)Patients Receiving

Cholesterol Screening (%)

18–29 0.730–39 2040–49 4950–59 2960–69 0.7

Adapted from J Community Health.6

A Symposium: Lipid-lowering Interventions in Managed Care Settings/Fox and Jones

April 16, 2001 THE AMERICAN JOURNAL OF MEDICINEt Volume 110 (6A) 25S

lesterol screening. Screening was carried out in only 20%of patients 30 to 39 years of age, 49% of those 40 to 49years old, and 29% of those 50 to 59 years of age. Davis etal9 found that screening for primary prevention at oneMCO was somewhat more effective. They reviewed therecords of 1,004 members (aged 40 to 64 years) of a singlehealth plan and found that 84% had at least one totalcholesterol level recorded over the previous 6 years. Inthis group of patients, the rate of cholesterol screeningwas highest among patients with hypercholesterolemia(99%), hypertension (96%), and diabetes (94%) andamong patients 60 to 64 years of age (94%). One limita-tion of the study was that the investigators were unable tofind the records of 20% of the patients enrolled during theperiod evaluated. If none of these patients had beenscreened, the overall percentage would fall to 67%.

Given that secondary prevention involves hyperlipid-emic patients with documented CHD who, in manycases, had already had a CHD-related cardiovascularevent, it is remarkable that screening for these patientsappears to be no better than that for primary prevention.Majumdar et al10 evaluated screening and treatment forsecondary prevention in a review of 2,938 records from37 community-based hospitals. Of the patients whoserecords were reviewed, 622 had previously establishedcoronary artery disease and hyperlipidemia (their totalcholesterol was .200 mg/dL or they were receiving treat-ment with lipid-lowering drugs). Only 65% of the pa-tients being treated with lipid-lowering drugs had serumlipids evaluated. Another recent study showed that 33%of patients with cardiovascular disease being treated in aprimary care setting were not screened with lipid pan-els.11 Finally, Flanagan et al12 evaluated a cohort of 1,015men and women with documented CHD who were beingtreated in a primary care setting. Only 18% of the menand 26% of the women had serum cholesterol measure-ments in their medical records.

Beyond measuring LDL-C levels regularly, physiciansmust take into account the patient’s CHD risk factors.Sometimes patients do not have LDL-C levels that reachthe recommended drug initiation level but still exceed theNCEP goal level, even with dietary therapy. The NCEPrecommendations call for physicians to exercise clinicaljudgment in determining appropriate therapy for thesepatients.3 Good risk factor management will indicate cer-tain patients whose lipid levels do not reach the drug ini-tiation level but who will still benefit from drug therapy.That some patients in the hyperlipidemia outcomes man-agement program were receiving such treatment eventhough they did not need it to reach goal levels indicatesthat the prescribing physicians were using their clinicaljudgment to determine the best course of treatment giventhe patients’ risk factors.

Administering TreatmentGotto13 has updated the analysis of Sempos et al14 usingrecent population data and the results of Air Force/TexasCoronary Atherosclerosis Program Study (AFCAPS/Tex-CAPS).15 He concluded that only 7% of the more than 21million US citizens eligible for lipid-lowering therapy arecurrently being treated. Furthermore, only 4% of patientseligible for primary prevention and 14% for secondaryprevention are receiving therapy.11 These findings areconsistent with results from more detailed, but smaller-scale, analyses.

Other primary prevention studies are consistent withthese results. Wicklmayer et al16 evaluated a cohort of 234patients with hypertension who were receiving regularmedical care; 26% of these patients had previously un-known diabetes, and 41% had impaired glucose toler-ance. The mean total serum cholesterol in the patientswith previously known diabetes was 276 mg/dL and thatin patients with normal glucose tolerance was 260 mg/dL.None of these patients was receiving lipid-lowering ther-apy. Results from a somewhat older study are similar.Hudson et al17 reviewed the records of 450 patients beingtreated in three different community practice settings.Only 47% of patients with total cholesterol .200 mg/dLand 64% of those with total cholesterol .240 mg/dL werereceiving any intervention.

Treatment of hyperlipidemia in patients with CHD isalso relatively rare. Majumdar et al10 reported that only37% of a cohort of patients with coronary artery diseaseand hyperlipidemia were receiving lipid-lowering drugs.McBride et al11 reviewed the records of 603 patients withcardiovascular disease and noted that 55% were receivingdietary counseling and only 33% were being treated withcholesterol-lowering medications. Ostor et al18 evaluatedtreatment of 546 patients with CHD, 46% of whom hadtotal serum cholesterol over 213 mg/dL. Only 22% of thetotal patient sample (less than one half of those withclearly elevated total cholesterol) were being treated withlipid-lowering drugs. Hoerger et al19 reported that 82%of adults with CHD are not at their NCEP goal of LDL-Cunder 100 mg/dL, a major reason being that 65% receiveno treatment. Most surprisingly, Khan et al20 recentlyreported that only 9% of patients hospitalized for a vali-dated acute myocardial infarction were discharged with aprescription for lipid-lowering drugs.

Making Treatment EffectiveEven when patients are identified and treated, most donot reach their NCEP goals for LDL-C. The L-TAP study4

determined how many patients taking lipid-loweringdrugs were meeting NCEP treatment goals. A total of4,888 patients from five US regions were included in theevaluation. As noted above, the success rates for the pa-tients in the three NCEP-defined risk categories—lowrisk, high risk, and established CHD—were 68%, 37%,


26S April 16, 2001 THE AMERICAN JOURNAL OF MEDICINEt Volume 110 (6A)

and 18%, respectively. A smaller-scale study that ob-served 90 randomly selected patients from a Veterans Ad-ministration Medical Center for 1 year found that only33% achieved treatment goals despite the fact that all ofthem were being treated with statins.21

Thus, all of these results indicate a need for programsto improve screening, treatment, and follow-up of pa-tients with hyperlipidemia. Several such interventionshave been carried out in MCO and other settings.

PROGRAMS TO IMPROVEMANAGEMENT OF HYPERLIPIDEMIAA number of approaches have been taken to improvescreening, treatment, and follow-up of patients with hy-perlipidemia. Results from several studies have docu-mented the effectiveness of physician education pro-grams in improving treatment of hypercholesterolemia.Casebeer et al22 reported an intervention designed to in-crease physicians’ use of adherence-enhancing strategiesin patients with hyperlipidemia conducted among 28physicians and 222 of their outpatients. The interventionconsisted of three audio conferences and chart remind-ers. Several measures indicated that the intervention waseffective in improving patient care. Patients whose phy-sicians were involved in the intervention reported signif-icantly increased knowledge of their hyperlipidemia andsignificantly reduced consumption of dietary fats. Mostimportant, the male patients in this group experienced asignificant reduction in serum cholesterol 9 months afterthe initiation of the intervention.

Ockene et al23 evaluated the effectiveness of a trainingprogram for physician-delivered nutrition counselingwith or without a structured office practice environmentfor nutrition management. The results showed that thecombination of physician counseling and an office envi-ronment geared toward nutrition management signifi-cantly enhanced implementation of the nutrition coun-seling sequence. The effect of this intervention on patientcholesterol levels was not assessed.

Keyserling et al24 used a randomized controlled designto compare standard care of patients with hyperlipidemiaversus care after use of a physician training program de-signed to encourage a structured assessment and treat-ment protocol. At the end of 1 year of follow-up, patientstreated by the trained physicians experienced a 4-mg/dLgreater reduction in total cholesterol than the controlgroup.

Thus, physician education programs can significantlyimprove the management of hyperlipidemia. The aim ofphase 2 of the hyperlipidemia outcomes managementprogram described by Patel and Perez1 is to implementeducational interventions for physicians that will im-prove their identification and treatment of hyperlipid-emic patients. A key aspect of this intervention will beinforming treaters of existing deficiencies in patient treat-

ment, follow-up, and drug use. Other programs that haveused this approach have documented significant im-provements in physician performance, particularly withrespect to drug use.25

Other programs take a highly integrated approach topatient care and generally involve a wider range of health-care professionals.26 These programs can include multi-disciplinary outpatient clinics, nurse- or pharmacist-ledoutpatient clinics, laboratory-centered programs, andeven Web-based programs.26 –30 Management programsaimed at lowering serum cholesterol and decreasing car-diovascular risk in patients with hyperlipidemia have metwith varying degrees of success.

Rutledge et al31 reported results from a program thatfocused on lifestyle modification to reduce the risk ofcardiovascular events in patients with documented CHD.They found significant reductions in body weight, totalcholesterol, and LDL-C over 2 years of follow-up. Therewas also a modest 2% reduction in cardiovascular events.Nola et al27 reported a pharmacist-directed lipid manage-ment program that included 51 patients who failed tomeet NCEP targets for LDL-C. Patients enrolled had areduction in LDL-C, whereas the control group had anincrease. In addition, 32% of the patients in the manage-ment program reached treatment goals versus 15% in thecontrol group. Risk factor prediction scores also im-proved in the program patients but worsened in controlsubjects.

In contrast to the above positive results, Jolly et al32

reported little positive effect of an integrated heart careproject among 597 patients (422 with myocardial infarc-tion and 175 with newly diagnosed angina). After 1 yearof follow-up there were no significant differences be-tween groups with respect to serum cholesterol (224 ver-sus 229 mg/dL) or other risk factors, including smokingcessation, fitness, and body mass index.

In summary, all of these types of programs have thepotential to improve physician performance and treat-ment outcomes for patients with hyperlipidemia. How-ever, this is not invariably the result. The effects of allinterventions must be carefully assessed to determinewhether program aims are met.

DRUG USE

More effective primary and secondary prevention in in-dividuals with hyperlipidemia will entail a very large in-crease in the number of patients receiving pharmacother-apy for this condition. Given the potentially huge in-creases in drug acquisition cost associated with effectivecholesterol-lowering therapy, MCOs must pay particularattention to treating patients in the most cost-effectivemanner. This necessitates attention to two key questions.



Should Primary Prevention Be Carried Out?There is no universal agreement that primary preventionis cost-effective in the managed care setting. For example,Pharoah and Hollingworth33 concluded that lipid-lower-ing therapy in middle-aged or elderly male patients withelevated serum cholesterol (.251 mg/dL) but no CHDwould not be cost-effective, the cost being £136,000 peryear of life saved (YOLS). However, other analyses indi-cate that primary prevention is cost-effective.

Jacobson32 reviewed the literature regarding the cost ofprimary and secondary prevention in patients with ele-vated serum lipid levels. This review showed that cost-effectiveness of different approaches to cardiovascularprevention varied widely in cost per YOLS (Table 2).Most importantly, the cost-effectiveness of primary pre-vention with statin therapy was much lower than that oftreatment of CHD and its consequences. Additional anal-yses have demonstrated that the cost per YOLS for pri-mary prevention falls well within the range of generallyimplemented medical therapies.35 Hay et al36 also con-cluded that intervention with statin therapy is cost-effec-tive in any patient with risk for coronary artery diseasethat exceeds 1% per year, which would include all pa-tients with existing coronary artery disease or diabetesmellitus, many more patients than would be treated un-der existing NCEP guidelines.

How Can We Improve Drug Use?Drug use for the management of hyperlipidemia can besubstantially improved by individualizing the agent anddose to meet the needs of each patient. Treatment shouldbe aimed at attaining each patient’s NCEP goal. Under-treatment that does not significantly reduce cardiovascu-lar risk is ineffective; any funds used for such therapy will

be wasted. Conversely, overtreatment resulting in LDL-Creductions in excess of those required to meet NCEP tar-gets might not provide any additional risk reduction35;excess funds spent on these patients could be used to treatothers. The results from phase 1 of the hyperlipidemiaoutcomes management program suggested that statinswere not being used in the most cost-effective mannerpossible. Certainly, treatment was not guided to choosethe least costly agent and dose compatible with theLDL-C reduction required. Indeed, failure to make use ofthe most cost-effective drugs available is a common prob-lem among health plans.38

For many years, managed care plans have been imple-menting drug formularies to administer pharmaceuti-cals. One health maintenance organization (HMO), Kai-ser Permanente of Colorado, found the use of a formularyto be a good way to control drug costs and provide qualitycare for their patients.39 Formularies are considered to benot merely a cost-cutting measure, but rather a way toimprove drug utilization by encouraging use of the mostappropriate drug for the patient.40 Another HMO foundthat the pharmacy and therapeutics committee that over-sees the formulary was able to decrease inappropriateprescribing of antimicrobials by performing drug useevaluations and developing treatment algorithms,41 stepsthat will also be taken in subsequent phases of this hyper-lipidemia outcomes management program. Also similarto this program, one HMO found that physician educa-tion initiatives combined with formulary revision weresuccessful in making prescribing more cost-effectivewithout restricting physicians or patients.42

MCOs often fail to incorporate pharmacoeconomicdata into formulary decision making.43 In fact, one recent

Table 2. Cost-effectiveness of Different Approaches to Cardiovascular Prevention

InterventionCost per Quality-Adjusted

Life Year (US $)

Highly cost-effectiveSmoking-cessation counseling (50-yr-old man) 1,300b-blocker after myocardial infarction 3,600Cholesterol reduction (population strategy) 3,200Coronary artery bypass graft (left main disease) 9,200Statin therapy (secondary prevention) 12,000

Relatively cost-effectiveExercise (asymptomatic 35-yr-old man) 22,400Hypertension therapy (hydrochlorothiazide) 25,400Statin therapy (primary prevention) 20,000–40,000Renal dialysis (benchmark index) 40,000

Least cost-effectiveCoronary artery bypass graft (mild angina, 1-vessel disease) 72,000Cardiac care unit (low probability of myocardial infarction) 88,700Heart transplant (50 yr of age, terminal disease) 100,000Electrocardiogram testing (asymptomatic 40-yr-old man) 124,000

Reprinted with permission from Curr Opin Lipidol.32



survey indicated that only 37% of plans employ an indi-vidual whose primary function is drug assessment.44 Onepotentially effective approach to optimizing drug treat-ment and reducing formulary costs is to employ a phar-macy benefit manager, as many MCOs do. Such an indi-vidual can promote cooperation among the differentconstituencies within an MCO, including physicians,pharmacists, patients, and payers.45 Most pharmacy ben-efit managers look for quality when making formularydecisions, seeking drugs that are effective and safe whilealso saving costs.25 One survey of pharmacy benefit man-agers found that their use of cost-effectiveness studies waslimited by the fact that the populations studied are oftendifferent from the ones they treat.46 Therefore, qualityimprovement programs such as the one we describemight serve as a model for using data from a plan’s ownpatients to guide formulary decisions.

In phases 2 and 3 of this program, results from phase 1will be analyzed to provide such information about drugquality. The comparable efficacy found among all statinsstudied indicates that consideration of drug acquisitioncosts can be a valid parameter in hyperlipidemia. Promo-tion of individually optimized lipid-lowering therapy isone of the goals of subsequent phases of the hyperlipid-emia outcomes management program.

CONCLUSIONS

Epidemiologic data clearly indicate that hyperlipidemiaaffects a large portion of the patients enrolled in anyMCO. Improved screening, the aging of the populationand subsequent increases in CHD risk,47 and increasedneed for antihyperlipidemic therapy mean that MCOswill need to develop cost-effective strategies for the med-ical management of this condition. Phase 1 of the hyper-lipidemia outcomes management program described7 in-dicated two important limitations in the treatment of pa-tients in the 27 participating plans. First, .20% ofhyperlipidemic patients are not being effectively moni-tored during treatment. Second, statin therapy is not be-ing optimized for each patient to achieve target LDL-C atthe lowest cost. Thus, quality improvement programs areneeded to enhance overall management of this diseaseand to optimize formulary drug use. Phases 2 and 3 of thisprogram will aim to improve these aspects of hyperlipid-emia treatment.

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lipid-lowering interventions in managed care settings

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