PREVENTIVE CARDIOLOGY FALL 2003204

Despite the large burden of cardiovascular disease onsociety, abnormal lipid levels, which are associatedwith an increase in coronary heart disease mortality,are not being adequately managed in many individu-als. Poor patient compliance with therapeutic lifestylechanges and lipid-modifying therapies contribute tothis treatment gap. If management of lipid levels is toreduce cardiovascular mortality effectively, poor com-pliance with treatment needs to be understood andaddressed. Educating and motivating patients to under-stand the need for compliance with continued therapyis an important step for ensuring that the benefits oflipid management cited in clinical trials are translatedto the general population. This will require a proactiveapproach from both patients and physicians. Well-tol-erated and effective therapies may also help complianceby reducing the incidence of side effects and the needfor complex dosing regimens. Suboptimal treatment oflipid levels is currently limiting the effectiveness of pri-mary and secondary prevention of coronary heart dis-ease; methods for improving compliance should be akey strategy to overcoming this problem. (Prev Cardiol.2003;6:204–213) ©2003 CHF, Inc.

Many deaths from cardiovascular disease can beprevented if the risk factors contributing to the

disease are identified quickly and treated successful-ly. More than 75% of coronary patients receive someor all of their treatment in primary care.1 Becauseprimary-care physicians are the principal healthcare

contact for most patients, they are ideally positionedto identify those with cardiovascular risk factors andensure that approaches to prevent coronary heartdisease (CHD) are implemented and maintained.

Abnormal lipoprotein profiles (elevated total cho-lesterol and low-density lipoprotein cholesterol[LDL-C], elevated triglycerides, reduced high-densi-ty lipoprotein cholesterol [HDL-C]) are recognizedas important risk factors for the development ofCHD, and national guidelines for their managementhave been developed.2 However, despite the obviousbenefits in prevention of death and disability, man-agement of cardiovascular risk factors, such as ele-vated cholesterol levels, is currently inadequate.3,4

Several factors, including poor patient compliancewith treatment and a lack of adherence to guidelinesby physicians, are thought to contribute to this treat-ment gap.5,6 The aim of this review is to highlightthe current climate of undertreatment of CHD, dis-cuss the role of noncompliance in underminingeffective lipid management, and outline measuresthat may be used to increase compliance.

CURRENT LIPID MANAGEMENTPRACTICESEpidemiologic studies have shown an associationbetween elevated cholesterol levels and increased car-diovascular mortality.7,8 Furthermore, numerouslarge-scale clinical trials of both primary9,10 and sec-ondary11–14 prevention have demonstrated that low-ering LDL-C reduces cardiovascular events and mor-tality. In addition, patients with hypertension andaverage or below-average cholesterol levels have beenshown to benefit from a reduction in cardiovascularevents with lipid-lowering therapy.15 To reduce theburden of CHD, the National Cholesterol EducationProgram Adult Treatment Panel (NCEP ATP) guide-lines have been developed to recommend lipid levelsand treatment options depending on the risk status ofthe patient. These guidelines have recently beenupdated and the categories of risk extended (Table I),2resulting in an increase of just over 10 million in thenumber of patients eligible for lipid-lowering therapyin the United States (Table I).16

Bridging the Treatment Gap: ImprovingCompliance With Lipid-Modifying Agentsand Therapeutic Lifestyle ChangesThomas Pearson, MD, PhD;1 Laurie Kopin, MS, RN, ANP2

CME PAPER

From the Department of Community and PreventiveMedicine,1 and The Strong Heart Center,2 University ofRochester Medical Center, Rochester, NYAddress for correspondence:Laurie Kopin, The Strong Heart Center, 2400 South ClintonAvenue, Building H, Suite 130, Rochester, NY 14618E-mail: laurie_kopin@urmc.rochester.eduManuscript received May 19, 2003;revised June 25, 2003;accepted July 10, 2003

www.lejacq.com ID: 2663

FALL 2003 PREVENTIVE CARDIOLOGY 205

There are several approaches to lowering choles-terol levels. Therapeutic lifestyle changes form thebackbone of lipid management, and all individualswith elevated lipid levels are encouraged to increasephysical activity and reduce dietary intake of satu-rated fat (<7% of total calories), cholesterol (<200mg/d), and total calories.2 Should this approachprove inadequate for reducing cholesterol, morestringent lifestyle changes, including the addition ofstanol/sterol ester margarines and fiber, would bebeneficial. Diets very low in total fat17 or very highin protein have not been proven safe and effectiveover extended periods of time and are therefore notrecommended for lipid modification. A reduction intotal fat intake to <10% could prove beneficial.17 Iflifestyle changes are insufficient to reduce LDL-C torecommended levels in high-risk or CHD patients,drug therapy should be considered. After meetinggoals for LDL-C, other lipoprotein particles thatmay foster atherosclerosis can be addressed.Triglyceride-rich lipoprotein particles (e.g., very-

low–density lipoprotein cholesterol) and their rem-nants are considered to be atherogenic. Because allatherogenic lipoprotein particles, including LDL-C,very-low–density lipoprotein cholesterol, andtriglyceride-rich lipoprotein remnants, are encom-passed within the term “non-HDL-C,” the NCEPATP III guidelines recommend controlling non-HDL-C levels when triglyceride levels are elevated(>200 mg/dL) (Table I).2

Hydroxymethylglutaryl coenzyme A reductaseinhibitors (statins) are well tolerated and effectivelipid-modifying agents.18 Consequently, NCEP ATPIII guidelines recognize statins as the first-line drugsin lipid management.2 The currently availablestatins—lovastatin, fluvastatin, simvastatin, pravas-tatin, and atorvastatin—and a recent addition tothe statin class, rosuvastatin, all vary in their abilityto lower LDL-C levels (Figure 1).19,20 Other agentsavailable for modifying lipid levels include bile acidsequestrants (resins), nicotinic acid (niacin), andfibrates, which can reduce LDL-C by 15%–30%,

Table I. Changes in Treatment Decisions from NCEP ATP II to NCEP ATP III Increases the Number of Patients Eligible forTreatment

NCEP ATP II NCEP ATP III

RISKCATEGORY

TREATMENTLEVEL**

(MG/DL)

LDL-CTARGET(MG/DL)

CHANGE IN RISKCATEGORY

TREATMENTLEVEL**

(MG/DL)

LDL-CTARGET(MG/DL)

NON-HDL-CTARGET†

(MG/DL)

PATIENTS NEWLYELIGIBLE FORTREATMENT*

(MILLION)

No CHD, <2riskfactors††

≥190 <160 No change ≥190 <160 <190 0

No CHD, 2+riskfactors††

≥160 <130 And 10-year risk‡

≤20%

i) 10-year risk‡

10%–20%≥130 <130 <160 4.108

ii) 10-year risk‡

<10%≥160 <130 <160 0

CHD ≥130 <100 Or CHD riskequivalent‡‡, 10-year risk‡ >20%

≥130(100–129

mg/dL) ***

<100 <130 6.101

NCEP ATP=National Cholesterol Education Program Adult Treatment Panel; LDL-C=low-density lipoprotein cholesterol;non-HDL-C=non high-density lipoprotein cholesterol; CHD=coronary heart disease; *data from Am J Cardiol.2002;89(suppl):8C–22C.16 **LDL-C level at which lipid-lowering treatment is recommended; †non-HDL-C targets arerecommended for patients with elevated triglyceride levels (>200 mg/dL); ††risk factors include age (≥45 years for men; ≥55years for women), family history of premature CHD (in a first-degree male relative <55 years or first-degree female relative<65 years), current cigarette smoking, hypertension (blood pressure ≥140/90 mm Hg) or antihypertensive treatment, and lowHDL-C (<40 mg/dL); ‡10-year risk of CHD is calculated according to the Framingham risk assessment algorithm, which isincluded as part of the NCEP ATP III guidelines. Risk factors used to determine the Framingham risk score are age, totalcholesterol, HDL-C, systolic blood pressure, treatment for hypertension, and cigarette smoking; ‡‡CHD risk equivalentsinclude diabetes, a global 10-year risk >20%, or other clinical forms of atherosclerosis, for example peripheral artery disease,an ankle brachial index <0.9, or a prior transient ischemic attack or cerebrovascular event; ***lipid-lowering therapy optional ifpatients fail to meet LDL-C targets with lifestyle changes.2

5%–25%, and 5%–20%, respectively.2 Fibrates areprimarily indicated for lowering triglyceride levelswhen concentrations exceed 1000 mg/dL.21 Niacinmay also be used to lower triglyceride levels andelevate HDL-C levels by up to 30%.22 Ezetimibe, arecently approved cholesterol absorption inhibitor,has been shown to reduce LDL-C by approximate-ly 17%.23 These agents can also be used in combi-nation with statins to further modify lipid levelsand help patients achieve guideline targets.

BENEFITS OF MEETING GUIDELINETARGETS AND THE CURRENTTREATMENT GAPAggressively lowering LDL-C levels to guideline lev-els or below is associated with clinical benefits24 andis advocated in the NCEP-ATP III report.2 Despitethe reported benefits of lowering LDL-C to belowtarget levels, a large proportion of patients (62%)receiving lipid management are still not meetingtheir cholesterol goals3 (Table II). With an increase inthe number of patients eligible for lipid-loweringtherapy, this is unlikely to improve unless the causesof undertreatment are addressed. The failure ofpatients to achieve their lipid targets may be a resultof several factors, including an inappropriate choiceor dose of a lipid-modifying agent, a lack of effec-tiveness of a lipid-modifying agent, a lack of follow-up to reassess treatment, a lack of awareness of treat-ment guidelines by the physician, or poor patientcompliance.3,6,25,26 Although each of these factorsshould be addressed individually, the problem ofpoor compliance is of particular concern. A studyhas shown that 60% of patients discontinue lipid-lowering therapy within the first year.27

Endothelial function can be improved or impairedquite rapidly by LDL apheresis28 or a high-fatmeal,29 respectively. However, lipid lowering needsto be maintained if it is to provide clinical benefits.Lipid-lowering therapy can reduce the signs ofischemia after 6 months,30 but the benefits in regardto cardiovascular events and mortality only becomeapparent after 1–1.5 years of continuous treat-ment,9–13 indicating that long-term compliance iscrucial. Furthermore, good treatment compliance isrequired for clinical benefits. In an analysis of theWest of Scotland Coronary Prevention Study,

patients with ≥75% compliance with pravastatintreatment were shown to have a reduced risk ofCHD death, nonfatal myocardial infarction (MI),and all-cause mortality, compared with patients whowere poor compliers.31 Clearly, if lipid managementis to be effective at reducing cardiovascular events,poor compliance with treatment needs to be under-stood and improved.

CAUSES OF NONCOMPLIANCEIt is evident that patients with chronic and asympto-matic diseases, such as dyslipidemia or hypertension,often have problems complying with treatment.Patients who do not perceive any physical harm fromtheir disease or immediate benefit from medicationmay believe therapy is not necessary and may bepoorly motivated to comply with treatment.Furthermore, patients may have incomplete or incor-rect information about CHD and its treatments,thereby contributing to noncompliance with theirtherapy.6 In the Lipid Treatment Assessment Project(L-TAP) survey, patients with a higher level ofeducation were more likely to reach recommendedlipid levels,3 possibly because they had a greaterunderstanding of their disease. Simons et al.27

reported that patients treated with other cardiovas-cular medications were 31% more likely to be com-pliant with lipid-lowering therapies. This may reflect

PREVENTIVE CARDIOLOGY FALL 2003206

Table II. Patients Reaching NCEP ATP II Goals in the Lipid Treatment Assessment Project*

PATIENT CATEGORY

LOW RISK HIGH RISK CHD

N 1143 2285 1460

NCEP ATP II LDL-C target <160 mg/dL <130 mg/dL <100 mg/dL

Patients at target (%) 68 37 18

*Adapted from Int J Cardiol. 2000;74(suppl):S23–S281; NCEP ATP=National Cholesterol Education Program AdultTreatment Panel; CHD=coronary heart disease; LDL-C=low-density lipoprotein cholesterol

0

10

20

30

40

50

60

70

Atorvastatin*

Fluvastatin*

Lovastatin*

Pravastatin*

Simvastatin*

Rosuvastatin**

Dose (mg/d)

10 20 40 80

Red

uct

ion

in

LD

L-C

(%

)

Figure 1. Comparison of low-density lipoprotein choles-terol (LDL-C) lowering with the current statins; *Am J Cardiol. 1998;81:582–58719**Am J Cardiol. 2001;88:504–508.20

a greater awareness of their disease and requirementfor treatment in these patients.

There are other patient-related causes for poorcompliance with lipid-lowering therapy. For exam-ple, some elderly patients may have poorer cogni-tive abilities and be less likely to comply with treat-ment regimens.32 The lack of a social support sys-tem, such as having no spousal support, also playsan important role in noncompliance.

Choice of therapy and dosing regimens can alsoaffect treatment compliance. In general, adherenceto treatment is worse for therapies that are poorlytolerated. Although resins are effective at reducingserum cholesterol levels, they are associated withundesirable side effects, such as bloating and con-stipation,21 and therefore suffer from high discon-tinuation rates (Figure 2).33 Similarly, flushing, aside effect common with niacin, may contribute tothe poor continuation rates observed with this ther-apy.33 The statins are well-tolerated therapies,which may explain why compliance rates aregreater for these agents compared with other treat-ments.34 Complex dosing regimens, such as thoseused in combination therapy, may also contributeto poor compliance.35

MODIFYING PATIENT BEHAVIOR TOPROMOTE COMPLIANCEThere are several approaches physicians can use topromote treatment compliance in patients. Thesemethods require a proactive approach from thephysician to engender compliant behavior.

EducationPatient education can play a large role in promot-ing compliant behavior and improving lipid man-agement. A patient’s perception of their diseaseaffects their motivation to comply with treatment.Adherence to medication is related to the balancebetween a patient’s belief about the necessity oftreatment and their concerns about adverse

events.36,37 Therefore, by reinforcing the need fortreatment and addressing a patient’s apprehen-sions, physicians can improve compliance.

Poorly informed patients may become noncom-pliant because they are unaware of the risks associ-ated with dyslipidemia and the need for continuedtreatment. For example, patients reaching choles-terol targets may consider themselves “cured” anddiscontinue treatment. Because primary care physi-cians are considered one of the most crediblesources of health care information,6 they are in agood position to help educate their patients aboutCHD and impress upon them the importance ofmaintaining pharmacologic therapy and lifestylechanges. Patients may not be able to recall all theinformation provided during a consultation,35 so itis important to reiterate key points, supply writteninformation where appropriate, and provide ade-quate follow-up care.

MotivationIn addition to educating patients, a personalizedexample of the affects of CHD can provide moti-vation to comply with therapy. For example, imag-ing techniques may be used to demonstrate the pro-gression of atherosclerotic disease within thepatient’s own arteries. However, a recent study hasreported that screening for coronary calcificationby electron beam tomography failed to motivatepatients to improve modifiable cardiovascular riskfactors.38 This may be due to the patient not recog-nizing the importance of coronary calcification as arisk factor. The importance of blood flow may bemore easily understood by patients and thereforedemonstrating stenosis by angiography could pro-vide an impetus to comply with lipid management.Unfortunately, the effectiveness of such anapproach has yet to be studied extensively andcould also be limited by the cost and availability ofappropriate health care resources.

Experience of a cardiovascular event can moti-vate individuals and, following an acute MI, 80% ofpatients reported having made spontaneous changesto deleterious lifestyle habits.39 Furthermore, initia-tion of statin therapy before discharge from the hos-pital following a cardiovascular event is associatedwith improved long-term compliance (after 1 year)compared with postdischarge initiation (77% vs.40%, respectively).40

Motivation can also be improved by encourag-ing the active involvement of patients in their owncare. For example, use of cholesterol tests in anambulatory care pharmacy program has beenshown to promote compliance, with rates as high as90% after 2 years of lipid-lowering therapy.41

Regular follow-up appointments to track changesin cholesterol levels may also motivate patients tocomply with treatment. For example, awareness ofpersonal cholesterol levels can promote lifestylechanges and reduce dietary fat intake.42

FALL 2003 PREVENTIVE CARDIOLOGY 207

0

10

20

30

40

50

60

70

80

90

Niacin Resin Statin

1 year

4 years

Pati

ents

Dis

con

tin

uin

g T

reatm

ent

(%)

Figure 2. Discontinuation rates reported for three com-mon classes of lipid-lowering agents Adapted from Am J Manag Care. 1999;5:437–444.33

SupportPatients receiving lipid management would benefitfrom the support of family, friends, and physicians.Family members can help remind patients to takemedications, attend appointments, and encouragetherapeutic lifestyle changes. Physicians can use fol-low-up appointments to ascertain whether treat-ment targets are being achieved and as an opportu-nity to monitor compliance, answer questions, con-tinue education, or provide motivation. Failure toachieve targets may be discouraging for some indi-viduals, and follow-up offers an opportunity to con-sider alternative pharmacologic treatments or dosetitration of ongoing therapies and to provideencouragement and positive reinforcement.

With continued education, motivation, and sup-port, it is hoped that compliance with therapy willbecome habitual. It has been observed that compli-ance rates are higher once patients have beenadherent with treatment for more than a year.43

PROMOTING COMPLIANT BEHAVIORIN PRACTICERates of compliance are notably higher in clinicaltrials and specialized lipid clinics compared with thegeneral population.34,44 This may be a result ofincreased physician involvement in clinical trials andof lipid clinics having more specialized experienceto draw on, or more time to educate and motivatepatients.34 Educating and motivating patients cantake time, and primary-care physicians are oftenbusy. This lack of time may also mean that primarycare physicians are less likely than specialists to beaware of new developments or to fully implementguidelines. However, other health care profession-als, such as advanced practice nurses, can help pri-mary-care physicians improve management of lipidlevels. For example, 98% of patients randomized toa nurse case-management program were compliantwith therapy 6 months after an MI compared with17% of patients receiving usual care.45 Even after 1year, compliance with the nurse case-managementprogram was greater than with usual care (90% and21%, respectively). A pharmacy counseling pro-gram, using weekly follow-up telephone calls topatients in the first 12 weeks of therapy, has alsoshown significant improvements in compliance andlipid profiles for up to 2 years compared withpatients receiving “usual care.”46 Similarly, a coach-ing program performed by a dietitian with a back-ground in education has been shown to improvetreatment, such that more patients reach recom-mended cholesterol levels (Table III).47 In the HeartProtection Study, more than 80% of patients in thestatin group were still adhering to their originalmedication after 5 years.14 This was attributed to acombination of approaches, that is, commitment ofnurses, clinician support for patients, and a highlevel of patient education throughout the trial.Adoption of these approaches in general practice

should help improve adherence to lipid-loweringtherapy. However, this may not always be feasiblebecause institutions or health care/managed careproviders may restrict resources or the availabilityof personnel that could help physicians to improvecompliance.

Support provided by family and friends is impor-tant for all patients who are engaged in therapeuticlifestyle changes or lipid-lowering therapy, particular-ly for those patients with impaired cognitive ability.By encouraging this, physicians may aid compliance.

TREATMENT TOLERABILITY, EFFICACY,AND COMPLIANCEConcerns about adverse events can negatively affectadherence to therapy.36,37 Lipid-lowering agentsassociated with frequently reported side effects, forexample niacin and resins, have poorer adherencerates than better-tolerated agents such as thestatins.33,34 The most common adverse effect withniacin is flushing of the skin, and this can proveintolerable to many patients.21 Resins are associatedwith gastrointestinal adverse effects, such as bloatingor constipation, that can occur in up to 30% ofpatients.21 Statins are considered to be well-toleratedlipid-modifying agents; however, the recent with-drawal of cerivastatin, due to several cases of fatalrhabdomyolysis, has attracted attention to statin-associated myopathy and prompted a clinical adviso-ry recommending cessation of therapy when musclepain or weakness is associated with creatine kinaseelevations 10 times the upper limit of normal.48 Therisk of fatal rhabdomyolysis with most statins is verylow (less than 1 death/million prescriptions) but wasfar greater for cerivastatin, particularly when used athigh doses or in combination with gemfibrozil, thanfor the other statins.48 However, the risk of rhab-domyolysis is outweighed by the clear benefits of thecurrently available statins for preventing cardiovas-

PREVENTIVE CARDIOLOGY FALL 2003208

Table III. The Effect of Coaching* on TotalCholesterol Levels after 6 Months in Patients Engaged inLipid-Lowering Therapy**

LIPID-LOWERING THERAPY

YES NO

With coaching 185 mg/dL(n=67)

208(n=40)

Without coaching 209 mg/dL(n=67)

222 mg/dL(n=45)

*Patients were contacted at 6 weekly intervals viatelephone call by a dietitian with a background ineducation and in working with individuals withcardiovascular diseases. Patients were coached to beaware of, and take responsibility for, the achievement andmaintenance of target cholesterol levels. **Adapted fromJ Clin Epidemiol. 2002;55:245–252.47

cular events, and their appropriate use should not bediscouraged.48 Indeed, the reports of rhabdomyoly-sis could dissuade more informed patients fromadhering to therapy. With patients aware of the myo-pathic potential of statins, physicians need to explainthis small risk of rhabdomyolysis in context with thelarge benefits associated with statin therapy. Theincidence of less serious adverse myopathic effects,such as nonspecific muscle aches without creatinekinase elevations (myalgia), are generally reported tobe about 5% in clinical trials, although this is not sig-nificantly different from that reported with placebo-treated patients.48 Physicians should be alert to thesigns and symptoms of myopathy and to whichpatient populations are at risk. Myopathy is morelikely to occur at higher statin doses than low onesand with certain concomitant medications like gem-fibrozil. Patients who are frail, of advanced age, orwho have multisystem diseases like renal insufficien-cy are at increased risk of statin-induced myopathy.48

However, many of these patients are at risk of devel-oping myopathy independently of statin therapy andmay mistakenly attribute muscle pain to the statinand discontinue treatment. Myopathy can also occurwith the use of fibrates, with a similar incidence tothat reported with statins.21

High-risk patients or those with established CHDoften find it harder to reach lipid targets comparedwith low-risk individuals,3 possibly because theirNCEP ATP III LDL-C targets are lower or their pre-treatment cholesterol levels are more elevated abovetarget. To help these individuals reach their LDL-Cgoal, high doses of lipid-modifying agents and/orcombination therapy may be required. However,both these approaches have the potential to increaseboth side effects and the complexity of dose regi-

mens, which may negatively affect compliance.Rosuvastatin, a recent addition to the statin class, ispromising, as it has been demonstrated to be moreefficacious than the current statins at reducing LDL-C and could enable more patients to achieve treat-ment goals, thereby reducing the need to titratedoses (Table IV).49 Additional compounds like eze-timibe23 and better-tolerated resins like coleseve-lam50 have also been developed to help improvetreatment and compliance.

CONCLUSIONTreatment of elevated cholesterol levels is impor-tant to reduce the burden of cardiovascular mor-bidity and mortality. However, despite the obviousbenefits of lowering lipid levels to those recom-mended by national guidelines, substantial numbersof patients are failing to reach their targets.

Poor patient compliance with lipid-loweringtherapies may be a major factor in the undertreat-ment of hyperlipidemia, and it can severely reducethe effectiveness of treatment. Promoting compli-ance with treatment is important if lipid levels areto be managed effectively. Primary-care physicianscan help to improve compliance and help moreindividuals reach guideline-recommended LDL-Clevels by educating and motivating patients them-selves and/or enlisting the support and expertise ofother specially trained health care providers such asnurse case managers and registered dietitians.Prescribing potent, efficacious, well-tolerated lipid-lowering agents may help many patients achievetheir recommended levels of LDL-C.Disclosure: Thomas Pearson, MD, has received funding fromAstraZeneca, Bristol-Myers Squibb, Johnson & Johnson, KOSPharmaceuticals, Merck, Novartis, Pfizer, and Schering Plough.

FALL 2003 PREVENTIVE CARDIOLOGY 209

Table IV. Comparison of Rosuvastatin and Atorvastatin at Achieving Treatment Targets and Needing Dose Titration*

ROSUVASTATIN ATORVASTATIN

STARTING DOSE (MG/D) 5** 10** 10**

12 weeks

Reduction in LDL-C (%) 46 50 39

Patients achieving targets (%)† 86 89 73

52 weeks

Reduction in LDL-C (%) 47 53 44

Patients achieving targets (%)† 88 98 87

Patients requiring dose titration (%) NA 18 41

Mean dose (mg/d) 9.3 13.4 20.8

*Adapted from Am Heart J. 2002;144:1044–1051.49 LDL-C=low-density lipoprotein cholesterol; NA=not available; **startingdose was maintained for 12 weeks; following the initial 12 weeks there was a 40-week titration period where individuals notachieving their National Cholesterol Education Program Adult Treatment Panel II target had the dose of study drugsequentially doubled until targets were attained; †National Cholesterol Education Program Adult Treatment Panel II targets

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33 Hiatt JG, Shamsie SG, Schectman G. Discontinuation ratesof cholesterol-lowering medications: implications for pri-mary care. Am J Manag Care. 1999;5:437–444.

34 Tsuyuki RT, Bungard TJ. Poor adherence with hypolipidem-ic drugs: a lost opportunity. Pharmacotherapy.2001;21:576–582.

35 Eraker SA, Kirscht JP, Becker MH. Understanding andimproving patient compliance. Ann Intern Med. 1984;100:258–268.

36 Horne R. Patients’ beliefs about treatment: the hiddendeterminant of treatment outcome? J Psychosom Res.1999;47:491–495.

37 Horne R, Weinman J. Patients’ beliefs about prescribedmedicines and their role in adherence to treatment in chron-ic physical illness. J Psychosom Res. 1999;47:555–567.

38 O’Malley PG, Feuerstein IM, Taylor AJ. Impact of electronbeam tomography, with or without case management, onmotivation, behavioral change, and cardiovascular risk pro-file. JAMA. 2003;289:2215–2223.

39 Shepherd J, Alcalde V, Befort P-A. International comparisonof awareness and attitudes towards coronary risk factorreduction: the HELP study. Heart European Leaders Panel.J Cardiovasc Risk. 1997;4:373–384.

40 Muhlestein JB, Horne BD, Bair TL, et al. Usefulness of in-hos-pital prescription of statin agents after angiographic diagnosisof coronary artery disease in improving continued complianceand reduced mortality. Am J Cardiol. 2001;87:257–261.

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41 Bluml BM, McKenny JM, Cziraky MJ. Pharmaceutical careservices and results in project ImPACT: hyperlipidemia. JAm Pharm Assoc (Wash). 2000;40:157–165.

42 Aubin M, Godin G, Vezina L, et al. Hypercholesterolemiascreening. Does knowledge of blood cholesterol level affectdietary fat intake? Can Fam Physician. 1998;44:1289–1297.

43 Avorn J, Monette J, Lacour A, et al. Persistence of use oflipid-lowering medications: a cross-national study. JAMA.1998;279:1458–1462.

44 Yates S, Annis L, Pippins J, et al. Does a lipid clinic increasecompliance with National Cholesterol Education ProgramTreatment Guidelines? Report of a case-matched controlledstudy. South Med J. 2001;94:907–909.

45 DeBusk RF, Miller NH, Superko HR, et al. A case-manage-ment system for coronary risk factor modification afteracute myocardial infarction. Ann Intern Med. 1994;120:721–729.

46 Faulkner MA, Wadibia EC, Lucas BD, et al. Impact of phar-macy counseling on compliance and effectiveness of combi-

nation lipid-lowering therapy in patients undergoing coro-nary artery revascularization: a randomized, controlledtrial. Pharmacotherapy. 2000;20:410–416.

47 Vale MJ, Jelinek MV, Best JD, et al. Coaching patients withcoronary heart disease to achieve the target cholesterol: amethod to bridge the gap between evidence-based medicineand the “real-world”—randomised controlled trial. J ClinEpidemiol. 2002;55:245–252.

48 Pasternak RC, Smith SC, Bairey-Mertz CN. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. JAm Coll Cardiol. 2002;40:567–572.

49 Olsson AG, Istad H, Luurila O, et al. Effects of rosuvastatinand atorvastatin compared over 52 weeks of treatment inpatients with hypercholesterolemia. Am Heart J. 2002;144:1044–1051.

50 Davidson MH, Dillon MA, Gordon B, et al. Colesevelamhydrochloride (cholestagel): a new, potent bile acid seques-trant associated with a low incidence of gastrointestinal sideeffects. Arch Intern Med. 1999;159:1893–1900.

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CME QUESTIONS AND ANSWERS

ACCREDITATION: The University of California, Davis, Health System is accredited by the Accreditation Council for Continuing MedicalEducation (ACCME) to sponsor continuing medical education for physicians.

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the ACCME through the joint spon-sorship of Oakstone Medical Publishing and Continuing Medical Education, UC Davis Health System. This CME activity was planned in accor-dance with the ACCME essentials for enduring materials. Length of time has been determined to be 1 hour. Please read the date of releaseand date of approval. This activity is approved for two years from the date of original release: November 2003.PHYSICIAN CREDIT: Continuing Medical Education at the University of California, Davis, Health System designates this continuing med-ical education for 1 hour in Category 1 of the Physician’s Recognition Award of the American Medical Association and the CertificationProgram of the California Medical Association. No partial credit is allowed for this CME activity.FACULTY DISCLOSURE: In accordance with standards of the ACCME and the guidelines of the Association of American Medical Colleges,the authors of this material have been asked to disclose any real or apparent conflicts of interest which may have a direct bearing on the subjectmatter presented. Authors are expected to disclose: 1) any significant financial interests or other relationships with manufacturers of commer-cial products and/or providers of commercial services discussed in their presentations; and 2) any “off-label” uses for pharmaceutical or medicaldevice products discussed in their materials. The intent of this disclosure is not to prevent authors with significant financial or other relationshipsfrom making presentations, but rather to provide participants with information with which they can make their own judgments. AUTHOR DISCLOSURE: T. Pearson is an advisor/consultant for Bristol-Myers Squibb, AstraZenca, KOS Pharmaceuticals, and J&J Merck;has recieved research grants from AstraZeneca, Merck, KOS Pharmaceuticals, and Bayer; and is a member of the speakers bureau of Bristol-MyersSquibb, AstraZeneca, J&J Merck, Pfizer, Bayer, KOS Pharmaceuticals, Merck, and Schering-Plough Merck. L. Kopin is a member of the speak-ers bureau of Pfizer, KOS Pahrmaceuticals and Merck.HOW TO OBTAIN CME CREDIT: To obtain CME credit, the University of California, Davis, Health System, Continuing MedicalEducation requires that you complete and return the answer sheet and program evaluation form with a check for $25, or you may fax thematerials with Visa/MasterCard information for payment. Checks should be made payable to Regents of the University of California and mailedto: Continuing Medical Education, UC Davis Health System, 3560 Business Drive, Suite 130, Sacramento, CA 95820.

To pay by Visa/Mastercard, please complete the entire application to include credit card number, expiration date and name of cardholder.You may fax this information to (916) 736-0188.

Upon completion of the above, your certificate of credit will be mailed to you within 4 weeks. All required information for enduringmaterials are located at the Office of Continuing Medical Education, UC Davis Health System, 3560 Business Drive, Suite 130, Sacramento,CA 95820. Any questions about this process may be directed to Pamela Stotlar-McAuliffe at (916) 734-5393; pamela.stotlar-mcauliffe-@ucdmc.ucdavis.edu.FACULTY ADVISOR: Ezra A. Amsterdam, MD, Professor of Medicine, Division of Cardiovascular Medicine, University of California,Davis, School of Medicine, and Director, Cardiac Care Unit, University of California, Davis, Medical Center, Sacramento, CA OBJECTIVE AND TARGET AUDIENCE: All primary care physicians and cardiologists are eligible to receive credit. At the conclusionof this activity, participants should be able to: 1) summarize the important points discussed in the paper reviewed; 2) identify patients to whomthe paper is relevant; 3) modify management practices as new information is learned; and 4) identify deficiencies in their knowledge base.

1. All of the following statements regarding currentlyavailable lipid-lowering drugs are true except:A. The risk of fatal rhabdomyolysis is <1 per mil-

lion patients treatedB. The risk of myopathy with statins is dose

relatedC. The risk of myopathy is increased with com-

bined statin and fibrate therapyD. It is currently recommended to stop statin ther-

apy if blood creatine kinase level increases tofive-fold normal

E. The risk of myopathy with statins is increasedin patients with renal failure

2. All of the following statements are true except:A. Fewer than 50% of all hypercholesterolemic

individuals currently achieve recommendedlow-density lipoprotein cholesterol goals

B. A higher proportion of patients without coro-nary heart disease than with coronary heartdisease are at low-density lipoprotein choles-terol goal

C. It has been reported that a majority of patientsdiscontinue statin therapy after 1 year

D. Education level has been shown to correlatewith compliance with lipid-lowering therapy

E. Measurement of coronary artery calciumscore by electron beam computed tomogra-phy has been shown to improve compliancewith lipid-lowering therapy

3. All of the following statements are true except:A. Lipid-lowering therapy reduces evidence of

myocardial ischemia within 6 monthsB. Lipid-lowering therapy improves endothe-

lial functionC. A single high-fat meal can impair endothelial

functionD. Cardiac events are reduced after 2 years of

lipid-lowering therapyE. Lipid-lowering therapy has not been associat-

ed with reduction of all-cause mortality

Insert your answers on the response page

FALL 2003 PREVENTIVE CARDIOLOGY 213

(Please check the single BEST answer)

1. A___ B___ C___ D___ E___2. A___ B___ C___ D___ E___3. A___ B___ C___ D___ E___

PROGRAM EVALUATION1. Did the material presented in this educational activity

meet the stated learning objectives?[ ] Yes [ ] No

2. Please rate the contents of this activity using the fol-lowing scale:1=Poor; 2=Fair; 3=Good; 4=Very Good; 5=Excellent

(circle the response for each question)Poor Excellent

Timely and up to date? 1 2 3 4 5Practical? 1 2 3 4 5Relevant to your practice? 1 2 3 4 5

3.Are there any other topics you would like to have seenaddressed in this activity?[ ] Yes (please specify): ______________________________[ ] No

4.Please describe any changes you plan to make in yourclinical practice based on the information presented inthis program. _________________________________________________________________________________________

5.Did you detect any commercial bias in this activity?[ ] Yes [ ] NoIf yes, please describe: _________________________________________________________________________________________________________________________________________________

6. Any other comments/suggestions for future education-al activities relating to preventive cardiology?_____________________________________________________________________________________________________________________________________________________________________

POST-TEST RESPONSES

Please type or print clearly:Re: Pearson T, Kopin L. Bridging the treatment gap: improving compliance with lipid-modifying agents and therapeutic

lifestyle changes. Prev Cardiol. 2003;6:204–213.

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INSTRUCTIONS:In order to complete this educational activity successfully, you must:[ ] Complete the post-test.[ ] Complete the program evaluation form.[ ] Enclose a check for $25 payable to: Regents of the University

of Californiaor[ ] Submit Visa/MasterCard information.

[ ] Mail or fax your completed answer sheet and check to: ContinuingMedical Education, UC Davis Health System, 3560Business Drive, Suite 130, Sacramento, CA 95820

In order to receive CME credit, the answer sheet must be receivedby November 2005.

Thank you.