N A T I O N A L I N S T I T U T E S O F H E A L T HN A T I O N A L H E A R T , L U N G , A N D B L O O D I N S T I T U T E

N a t i o n a l C h o l e s t e r o l E d u c a t i o n P r o g r a m

CHOLESTEROL

LOWERING IN

THE PATIENT

WITH CORONARY

HEART DISEASE

PHYSICIAN

MONOGRAPH

100

LDL

CHOLESTEROL LOWERING IN THE

PATIENT WITH CORONARY HEART DISEASE

PHYSICIAN MONOGRAPH

NAT I O N A L IN S T I T U T E S O F HE A LT H

National Hear t , Lung , and Blood In s t i tu t e

Nat ional Cho l e s t e r o l Educat i on Program

NIH PU B L I C AT I O N

NO. 97-3794

SE P T E M B E R 1997

iii

Cholesterol and the CHD Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Review of the Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Recent Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Scandinavian Simvastatin Survival Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Cholesterol and Recurrent Events Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Post Coronary Artery Bypass Graft Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Meta-Analysis of Previous Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Review of Angiographic Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Unstable Plaque . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Magnitude of the Benefit From Cholesterol Lowering in CHD Patients . . . . . . . . . . . . . . . . . 4

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Overview of the ATP II Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Management of Cholesterol Levels In CHD Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Dietary Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Step II Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

How To Make the Step II Diet Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Physical Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Weight Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Diet Initiation, Monitoring, and Followup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Drug Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

When To Initiate Drug Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Drug Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Monitoring and Followup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

CONTENTS

iv

Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Role of the Physician . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Role of the Nurse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Role of the Registered Dietitian . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Role of the Pharmacist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Strategies To Enhance Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Summing Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Patient Handouts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Patient Instructions for Taking Statins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Patient Instructions for Taking Resin Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Patient Instructions for Taking Nicotinic Acid (Niacin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Additional Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Order Form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

CHOLESTEROL AND THE CHD PATIENT

Recent clinical trials have proven conclusivelythat lowering low density lipoprotein (LDL) cho-lesterol levels in patients with established coro-nary heart disease (CHD) sharply reduces therisk of myocardial infarction (MI), death fromCHD, and death from all causes. The benefit ofcholesterol-lowering therapy extends even topatients with average cholesterol levels. Thegoal for cholesterol lowering in CHD patients isan LDL-cholesterol of 100 mg/dL or less.

In light of the evidence, cholesterol loweringshould be a routine feature of the clinical man-agement of CHD. Unfortunately, many CHDpatients are receiving inadequate or no therapyto lower cholesterol.

This monograph was developed to help physi-cians improve the health and prolong the lives ofpatients with CHD. It aims to do four things:(1) review the evidence that cholesterol loweringis highly beneficial in CHD patients, (2) summa-rize the basic Adult Treatment Panel II (ATP II)1

guidelines as they pertain to CHD patients, (3) provide guidance on initiating diet and drugtreatment, and (4) offer practical advice on waysto improve adherence.

REVIEW OF THE EVIDENCE

The presence of established CHD confers a highrisk for the occurrence of subsequent coronaryevents and CHD mortality. Men and womenwith CHD have about five to seven times therisk of developing a myocardial infarction asthose with no previous clinical manifestations ofcoronary disease. Recent observational studies

have shown that LDL-cholesterol levels are sig-nificant predictors of future MI in patients withestablished CHD. This relationship holds evenfor CHD patients with cholesterol levels in therelatively low range.

Over the past three decades, the medical commu-nity has been accumulating evidence regardingcholesterol lowering in patients with CHD.Three recent clinical trials—4S,2 CARE,3 andPost CABG4—that achieved large reductions incholesterol levels through the use of statin drugshave provided unequivocal evidence that lower-ing cholesterol produces large benefits in CHDpatients. These trials, in conjunction with meta-analyses of previous clinical trials and angio-graphic studies, support the National CholesterolEducation Program (NCEP) recommendationthat aggressive cholesterol lowering should be astandard element in the care of patients withCHD.

Evidence of the Benefits of LDL-Cholesterol Lowering in CHD Patients• Recent randomized clinical trials (4S,

CARE, and Post CABG)

• Meta-analysis of previous clinical trials

• Angiographic trials

Recent Clinical Trials

Scandinavian Simvastatin Survival Study

The Scandinavian Simvastatin Survival Study(4S)2 was a randomized placebo-controlled clinical trial involving 4,444 patients who had a history of angina pectoris or MI and serum

1

CHOLESTEROL LOWERING IN THE

PATIENT WITH CORONARY HEART DISEASE

2

cholesterol levels between 213 and 310 mg/dL.The patients (81 percent male, 19 percent female,ages 35 to 70 years at enrollment) were placed ona cholesterol-lowering diet and were randomizedto double-blind treatment with either the statindrug simvastatin or a placebo. The primary end-point was total mortality.

Over the median 5.4 years of followup, simva-statin therapy resulted in a mean lowering of 25 percent in total cholesterol and 35 percent inLDL-cholesterol. The treatment group experi-enced a 34 percent reduction in major coronaryevents, a 42 percent reduction in CHD mortality,a 37 percent reduction in revascularization proce-dures (coronary artery bypass surgery or angio-plasty), and a 30 percent reduction in total mor-tality. Older patients (≥65 years old) and womenalso showed a reduction in CHD morbidity andmortality with cholesterol lowering. In thisstudy, a very large degree of cholesterol loweringproduced no increase in noncardiovascular mor-tality—in particular, no increase in deaths fromcancers or from suicide, homicide, or accidents.

Key Findings From 4SCholesterol levels

25% ↓ in total cholesterol

35% ↓ in LDL-cholesterol

Endpoints

34% ↓ in major coronary events

42% ↓ in CHD mortality

37% ↓ in revascularization procedures

30% ↓ in total mortality

Cholesterol and Recurrent Events Trial

The Cholesterol and Recurrent Events (CARE)trial,3 a 5-year double-blind study, documentedfor the first time a benefit of cholesterol loweringin CHD patients with average cholesterol levels.The CARE study enrolled 4,159 patients (86 per-cent male, 14 percent female) ages 24 to 75 whohad suffered an MI in the 2 years before studyenrollment. Total cholesterol levels of partici-

pants averaged 209 mg/dL at study initiation.Pravastatin was used to lower cholesterol levels inthe treatment group, and the primary endpointwas death from CHD or symptomatic nonfatal MI.

Pravastatin therapy resulted in a mean reduction of 20 percent in total cholesterol and 28 percent in LDL-cholesterol. The treatment group had a 24 percent reduction in fatal CHD and nonfatal MIand a 27 percent reduction in revascularization procedures. Women and older patients (≥60 yearsof age) showed even greater reductions in majorcoronary events. As in 4S, the large reductions incholesterol levels produced no significant increasein noncardiovascular mortality, including deathsfrom cancers or from suicide, homicide, or acci-dents. Although there were more breast cancercases in the pravastatin group, no previous or ongoing trials with pravastatin or other statins have shown this connection. This study demon-strates the benefits of cholesterol lowering in CHDpatients whose cholesterol is average.

Key Findings From CARECholesterol levels

20% ↓ in total cholesterol

28% ↓ in LDL-cholesterol

Endpoints

24% ↓ in CHD mortality and nonfatal MI

27% ↓ in revascularization procedures

Post Coronary Artery Bypass Graft Trial

The Post Coronary Artery Bypass Graft (PostCABG) trial4 was a multicenter, double-blind, ran-domized, controlled trial of 1,351 patients (92 per-cent male, 8 percent female) ages 21 to 74 yearswith existing saphenous vein coronary bypass grafts(SVG) placed 1 to 11 years previously, with LDL-cholesterol levels between 130 and 175 mg/dL.This study compared the efficacy of aggressive versus moderate LDL-cholesterol-lowering therapyin delaying the progression of SVG atherosclerosisas measured by angiography after 4 to 5 years ontherapy.

3

Through the use of a combined regimen of lovastatin and cholestyramine resin, the aggres-sive cholesterol-lowering group achieved a meanLDL-cholesterol of 93 to 97 mg/dL, and the moderate cholesterol-lowering group achieved amean LDL-cholesterol of 132 to 136 mg/dL.

In the Post CABG trial, aggressive LDL-cholesterol lowering (to a mean level of 93 to 97 mg/dL) produced a 31 percent reduction inthe progression of atherosclerosis in the grafts, ascompared to moderate LDL-cholesterol lowering,and reduced the need for repeat revascularization.The results of this study support the NCEP rec-ommendation to lower LDL-cholesterol in CHDpatients to 100 mg/dL or less.

Key Findings From Post CABGCholesterol levels

LDL-cholesterol 93–97 mg/dL with aggressivelowering (vs. 132–136 mg/dL with moder-ate lowering)

Endpoints

31% ↓ in plaque progression

29% ↓ in revascularization procedures(p=0.03: not statistically significant whencorrected for multiple testing)

Meta-Analysis of Previous Trials

The 4S, CARE, and Post CABG trials provideconclusive proof of the benefits of cholesterol low-ering in CHD patients, but they are not the firststudies to demonstrate these effects. Their resultsare consistent with earlier trials that typicallyachieved lesser degrees of cholesterol lowering(approximately 10 percent in most cases). A1993 meta-analysis* by Rossouw, which appearsin the ATP II report1 and is based on earlieranalyses5,6 of secondary prevention trials, showedthat cholesterol lowering to a more modest extent

than in 4S, CARE, and Post CABG reduced nonfatal MI by approximately 26 percent, fatalMI by about 14 percent, and total mortality byabout 9 percent.

Meta-Analysis of Previous TrialsCholesterol levels

Modest cholesterol lowering (approximate-ly 10%)

Endpoints

26% ↓ in nonfatal MI

14% ↓ in fatal MI

9% ↓ in total mortality

Review of Angiographic Trials

Angiographic studies14 have shown that, inpatients with coronary atherosclerosis, intensivecholesterol lowering—often to LDL-cholesterollevels of 100 mg/dL or below—retards the rateof progression and in some patients leads toregression of atherosclerotic lesions. Favorableresults have been observed whether cholesterollowering was achieved by lifestyle modification(dietary therapy and physical activity), drugtherapy, or partial ileal bypass surgery. In thesestudies, relatively small improvements in lumendiameter were observed; these are unlikely toaccount for the quite large reductions thatoccurred in the incidence of clinical CHD events.The fact that these significant reductions havebeen observed in the treated groups after only 2 years of treatment most likely indicates thatthe instability of plaques (which leads to fissur-ing, thrombosis, and intramural hemorrhage) isreduced as well. A reduction in CHD eventsresulting from cholesterol intervention has beenobserved even in patients who were not selectedbecause of high cholesterol levels but had pre-treatment levels in the so-called “normal” range.

* Studies included in the 1993 meta-analysis: Medical Research Council’s low-fat diet trial,7 Medical Research Council’s soya-bean oil trial,8 Scottish Society of Physicians’ clofibrate trial,9 Stockholm Ischaemic Heart Disease Secondary PreventionStudy,10 Coronary Drug Project’s clofibrate trial,11,12 Coronary Drug Project’s niacin trial,11,12 and Program on the SurgicalControl of the Hyperlipidemias.13

4

Angiographic TrialsCholesterol levels

• Intensive LDL ↓ – often to 100 mg/dL orbelow

Results

• Slowed progression of plaque

• Regression of plaque in some patients

• Reduced CHD events

Unstable Plaque

To understand how modest regression in a smallnumber of lesions can be associated with a largeand relatively rapid reduction in the frequency ofclinical events, it is necessary to review the char-acteristics of the unstable lesion that typicallyprecipitates a clinical event.

Most patients who die from an MI have a throm-bosed arterial segment associated with a fissuredfibrous cap of an atherosclerotic plaque. Thistype of lesion constitutes only 10 to 20 percent ofall atherosclerotic lesions but accounts for 80 to90 percent of acute clinical events. Fissuring isassociated with a large accumulation of core lipidin the plaque and with a high density of lipid-laden macrophages in its thinned fibrous cap. Inthe clinical setting, intensive cholesterol loweringgreatly reduces the likelihood that plaques willundergo rupture and lead to clinical events suchas sudden death, MI, or worsening angina requir-ing coronary artery bypass graft or angioplasty.

The reduction of clinical events seen in theseangiographic trials can be best explained by the

relationship betweenthe lipid and foamcell content of theplaque and its likeli-hood of fissuring andby the effects of cho-lesterol lowering onplaque morphology.Trial results supportthe hypothesis that

cholesterol-lowering therapy selectively depletesor regresses that relatively small but dangerous

subgroup of fatty lesions containing a large lipidcore and dense clusters of intimal macrophages.As a result, these lesions are stabilized, their ten-dency to rupture is reduced, and the clinicalevent rate is decreased accordingly.

Magnitude of the Benefit From CholesterolLowering in CHD Patients

CHD patients have been shown in clinical trialsto experience large benefits from cholesterol low-ering. In 4S, CHD mortality was reduced by 42 percent and total mortality by 30 percent.Major coronary events were reduced by 34 per-cent in 4S and by24 percent inCARE. Estimatesfrom the CAREstudy suggestthat aggressivecholesterol-lower-ing treatment of1,000 CHDpatients over 5 years can be expected to avert153 cardiovascular events if the patients are sim-ilar to those in CARE, 207 if they are all over60, and 228 if they are all women. Estimatesderived from the work of the 4S authors suggestthat treatment of 1,000 CHD patients over 6 years can be expected to preserve the lives of40 of the 90 patients who would otherwise diefrom CHD, prevent 70 of the expected 210 non-fatal MIs, and avoid revascularization proceduresin 60 of 190 patients. Among the approximate-ly 3.5 million Americans with CHD and elevatedcholesterol levels similar to those of 4S patients,cholesterol lower-ing should preventabout 140,000deaths, 270,000MIs, and 585,900hospitalizations forCHD. An evengreater impact onthe lives and health of the 12 to 13 million people with CHD can be expected from extend-ing the eligibility criteria for aggressive therapyto those used in the CARE study.

Through cholesterol lowering, unstable lesionsare stabilized, their tendency to rupture isreduced, and the clinicalevent rate is decreasedaccordingly.

Treating only the 3.5 million 4S-like patients prevents 140,000 deaths, 270,000 MIs, and 585,900 hospitalizations

Extending the criteria for aggressive therapy tothose used in CARE willproduce an even greaterimpact.

5

Clearly, cholesterol lowering offers CHD patientsimpressive benefits. The trial data suggest thatthese effects are as large as, if not larger than,those from aspirin or beta-blockers. It should berecognized, however, that as worthwhile as it isto lower cholesterol in established CHD, oncethe extent of atherosclerosis in the coronaryarteries is as great as it is in CHD patients,plaque stabilization through cholesterol loweringcan go only so far. Thus, in 4S, the 42 percentreduction in CHD mortality means that 58 per-cent was left untouched. Given the very highbaseline rate of CHD death in patients withestablished CHD, the 58 percent that remainsafter cholesterol-lowering therapy is still anunacceptably high rate of CHD death. Withnewer agents that promise to lower LDL-choles-terol by 50 to 60 percent, the reduction in CHDrisk will probably be larger, but even so, theresidual morbidity and mortality from CHD isstill likely to be greater than in the populationwithout CHD. This implication of the clinicaltrial data reinforces the need for a strong com-plementary program of primary prevention tohelp reduce the burden of atherosclerosis in oursociety and prevent the development of CHD inthe first place.

Conclusion

Clinical trial evidence from the 4S, CARE, andPost CABG trials, as well as from meta-analysisof earlier trials and angiographic studies, showsthat aggressive cholesterol lowering in CHDpatients will reduce the risk for a future MI andCHD death, thereby improving the health andprolonging the lives of many CHD patients.The overall body of evidence supports the NCEPrecommendation to lower LDL-cholesterol inCHD patients to 100 mg/dL or less.

OVERVIEW OF THE ATP II GUIDELINES

The NCEP ATP II guidelines call for aggressivecholesterol lowering in patients with CHD orother clinical atherosclerotic disease—namely,MI, angina, CABG or angioplasty, peripheralarterial disease, abdominal aortic aneurysm, orsymptomatic carotid artery disease (see Table 1).These patients all have a very high risk for CHDevents and thus require intensive treatment tolower cholesterol levels. The goal of cholesterol-lowering therapy in patients with CHD or otheratherosclerotic disease is an LDL-cholesterol level≤100 mg/dL.

In CHD patients, the LDL goal is ≤100 mg/dL.

Table 1. Atherosclerotic Disease:Candidates for Aggressive LDL-Cholesterol LoweringCoronary Heart Disease

– Myocardial infarction

– Angina pectoris

– Unstable angina

– Stable angina

– Coronary artery procedures

– Coronary artery bypass surgery

– Angioplasty

Other Forms of Atherosclerotic Disease

– Peripheral arterial disease

– Abdominal aortic aneurysm

– Symptomatic carotid artery disease

All men and women who have established CHDshould have a fasting lipoprotein analysis forLDL-cholesterol determination on at least twooccasions, 1 to 8 weeks apart (see Figure 1). Ifthe two LDL-cholesterol values differ by morethan 30 mg/dL, a third test should be performed;

6

the average of all three would then be used.Blood samples should be collected from patientswho have fasted for at least 9 to 12 hours (i.e.,nothing by mouth of caloric value).

Table 2 summarizes the cutpoints for initiatingdietary therapy and, when appropriate, addingdrug treatment. If the LDL-cholesterol is higherthan 100 mg/dL, maximal dietary therapy with

the Step II diet (see page 8), together with physi-cal activity and weight control, should be initiat-ed. For many patients, this will be sufficient. Formany others, however, it will be necessary to adddrug treatment, since the goal LDL-cholesterol of100 mg/dL is quite low. If and when it becomesapparent that the target LDL-cholesterol cannotbe reached by diet and life habit changes alone,drug therapy should be considered.

Figure 1. Secondary Prevention in Adults With Evidence of CHD:Classification Based on LDL-Cholesterol

Do clinical evaluation(history, physical exam, and laboratory tests)

Evaluate for secondary causes(when indicated)

Evaluate for familial disorders(when indicated)

Consider influences of age, sex, and other CHD risk factors

Lipoprotein analysis*fasting, 9–12 hours

Average of 2 measurements1–8 weeks apart**

Higher than optimalLDL-cholesterol>100 mg/dL

OptimalLDL-cholesterol≤100 mg/dL

Individualize instruction on dietand physical activity level

Repeat lipoprotein analysis annually

Initiate therapy (see Table 2)

* Lipoprotein analysis should be performed when the patient is not in the recovery phase from an acute coronary or other medical event that would lower their usual LDL-cholesterol level.

** If the first two LDL-cholesterol tests differ by more than 30 mg/dL, a third test should be obtained within1–8 weeks and the average value of the three tests used.

7

In general, if the patient’s stable baseline LDL-cholesterol is ≥130 mg/dL, it is not likely to belowered to ≤100 mg/dL with dietary therapyalone, and a combination of diet and drug treat-ment is warranted. If the baseline LDL-choles-terol is 100 to 129 mg/dL, diet therapy should betried for 6 weeks. Whether to initiate drug ther-apy for patients whose LDL-cholesterol remainsbetween 100 and 129 mg/dL after intensivedietary therapy depends on a variety of factorsand must be left to the judgment of the physi-cian. Many authorities believe it is prudent toinitiate drug therapy to maximize reduction ofLDL-cholesterol levels, but the physician willhave to consider the potential side effects andcosts of drug therapy in arriving at a decision.Likewise, if the LDL-cholesterol level is between100 and 129 mg/dL after single-drug therapy, adecision to raise the dose or add a second drugwill have to be based on clinical judgment.

All CHD patients should be encouraged to main-tain life habit changes (diet, physical activity, andweight control) even when on drug therapy.These changes will not only help maximize thereduction in LDL-cholesterol and minimize thedose of medication but will also reduce CHD riskby other mechanisms, such as raising high densitylipoprotein (HDL) and lowering very low densitylipoprotein (VLDL) levels, lowering blood pres-sure and improving glucose tolerance, and lessen-ing the danger of acute coronary thrombogenesis.

MANAGEMENT OF CHOLESTEROL

LEVELS IN CHD PATIENTS

Measurement

The recommended lipoprotein analysis (see page 5)should be performed when the patient is metaboli-cally stable. If the patient has had an acutemyocardial infarction, cholesterol levels may belower than usual for up to 12 weeks thereafter, but a preliminary measurement of cholesterol during the acute phase provides an approximationthat can assist with initial management decisions.Any acute insult, such as an acute MI, can set into motion a series of metabolic responses.Mobilization of free fatty acids leads to elevatedtriglyceride levels and the depression of LDL- andHDL-cholesterol levels. If possible, a lipoproteinprofile should be obtained immediately on admis-sion (within a few hours of the MI), before thesemetabolic effects have accumulated and while lev-els may still reflect a patient’s pre-event cholesterolstatus. In addition, a lipoprotein profile should beobtained at a time close to discharge. If the LDL-cholesterol at discharge is ≥130 mg/dL, relativelyfirm decisions about cholesterol-lowering treat-ment can be made then, since the LDL level willlikely be higher later when the patient has notonly recovered from the acute event but reestab-lished normal habits.

CHD patients who have not had a recent acute MI but who are acutely ill, or those with recenttrauma, surgery, acute infection, a change in usual diet, weight loss, or pregnancy, should berescheduled for lipid testing because the lipid lev-els in such patients may not be representative oftheir usual levels.

Table 2. LDL-Cholesterol-Lowering Therapy in CHD Patients

Initiate Dietary Add DrugTherapy Treatment Goal

LDL-cholesterol level >100 mg/dL ≥130 mg/dL ≤100 mg/dL

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The choice of a laboratory is an important issuebecause there is variability in the accuracy andreliability with which laboratories measure cho-lesterol. The physician should seek a laboratorythat participates in a reliable standardization pro-gram, preferably one that has its lipid assaysstandardized through one of the NationalNetwork Laboratories of the Centers for DiseaseControl and Prevention.

To minimize the effects of posture, which canalter the cholesterol value by changing plasmavolume, venipuncture should be carried out inpatients who have been sitting for at least 5 min-utes, and the tourniquet should be used for asbrief a period as possible. It is preferable to col-lect the blood in tubes without anticoagulant (forserum) since NCEP ATP II cutpoints are serumvalues, but it is acceptable to use tubes contain-ing EDTA (ethylenediaminetetraacetic acid, forplasma). To convert plasma values to serum,multiply the plasma values by 1.03.

If the fasting triglyceride value is below 400 mg/dL, this value can be divided by 5 toestimate the VLDL-cholesterol level. Because the total cholesterol level is the sum of LDL-cho-lesterol, HDL-cholesterol, and VLDL-cholesterol,LDL-cholesterol can be calculated as follows:

For patients with triglyceride values of more than 400 mg/dL, estimation of LDL-cholesterolin this way is not accurate, and ultracentrifuga-tion in a specialized laboratory is required foraccuracy.

All patients with CHD and an LDL-cholesterol>100 mg/dL should be evaluated thoroughly toguide cholesterol management. The clinical eval-uation—history, physical examination, and labo-ratory tests—has several aims. The first is todetermine whether the elevated LDL-cholesterolis secondary to another condition, such as:

• Diabetes mellitus

• Hypothyroidism

• Nephrotic syndrome

• Obstructive liver disease

• Drugs (e.g., progestins, anabolic steroids, corti-costeroids, and certain antihypertensive agents)

A second aim is to determine whether a geneticdisorder is present. A family history and choles-terol measurement in the patient’s first-degreerelatives may uncover additional patients with agenetic dyslipidemia who need therapy beforethey develop clinical CHD. A third aim is to beable to use information about the patient’s overallCHD risk status, including age, sex, and otherCHD risk factors, in establishing a treatment pro-gram directed at the lipid problems.

Dietary Therapy

Dietary therapy is an essential element in thetreatment of all CHD patients whose LDL-choles-terol level is >100 mg/dL. Dietary therapyaddresses the major contributors to an elevatedLDL-cholesterol level: excess intakes of saturatedfat and cholesterol, and an imbalance betweenenergy expenditure and caloric intake leading toobesity. Accordingly, a program of dietary thera-py and life habit modification reduces the intakesof saturated fat and cholesterol, increases physicalactivity, and seeks to restore caloric balance tocontrol weight. The goal is not a temporary“diet,” but a permanent change in eating pat-terns, accompanied by increased physical activityappropriate for the patient’s cardiac status.

Step II Diet

The cornerstone of dietary therapy for the CHDpatient is the Step II diet (see box, page 9).Reduction of saturated fat intake is crucial, sincesaturated fat raises LDL-cholesterol more thanany other dietary component. Reduction of totalfat facilitates a decrease in saturated fat andcaloric intake but does not lower LDL-cholesterolper se. Dietary cholesterol raises the serum

LDL-=

Total–

HDL-–

TriglyceridesCholesterol Cholesterol Cholesterol 5

All quantities are in mg/dL.

9

cholesterol level in many people, and epidemio-logic studies suggest that it increases risk forCHD beyond its serum cholesterol-raising effect.Caloric balance is important for achieving desir-able weight; correcting obesity, even in mildlyoverweight patients, helps lower LDL-cholesterol,reduce VLDL-cholesterol and triglycerides, andraise HDL-cholesterol levels.

Step II DietSaturated fat <7 percent of total calories

Total fat ≤30 percent of total calories

Cholesterol <200 mg/day

Total calories To achieve and maintaindesirable weight

Dietary equations predict that the Step II dietwill reduce LDL-cholesterol levels by about 10 to20 percent in CHD patients who are consumingan average American diet. Many CHD patients,however, have higher intakes of saturated fat andcholesterol and higher serum cholesterol levelsthan average and will thus achieve an evengreater reduction in LDL levels.

How To Make the Step II Diet Work

The Step II diet should meet the RecommendedDietary Allowances while providing a variety offoods from all food types. Generally, dairy andmeat products should be of the low-fat or nonfatvariety, and meats should be lean. It is generallynot necessary or desirable to eliminate dairyproducts or meats (or any major food group, forthat matter) from a cholesterol-lowering eatingpattern. A variety of nutritious and palatablefoods can be consumed as part of a fat-modifieddiet aimed at lowering serum cholesterol levelsand reducing CHD risk. This overall eating pat-tern also may help prevent other diet-relatedchronic diseases.

To decrease the intake of saturated fat, total fat, andcholesterol, the emphasis of the Step II diet should be onconsumption of:

• fruits and vegetables

• breads, cereals, rice, legumes, and pasta

• skim or 1 percent milk and nonfat or low-fatmilk products

• lean meat, poultry, and fish

The following tips will help your patients choosefoods for the Step II diet. Deliver at least a fewof the most salient points yourself; the remaindercan be conveyed by a registered dietitian, otherqualified nutritionist, or member of your officestaff. Assistance from a dietitian can be particu-larly helpful in facilitating maintenance of theStep II diet in CHD patients.

To cut back on saturated fats, advise patients to choose:

• Poultry, fish, and lean cuts of meat. Removethe skin from chicken and trim the fat frommeat before cooking.

• Skim or 1 percent milk instead of 2 percent orwhole milk.

• Cheeses with no more than 3 grams of fat perounce. Cut down on full-fat processed, natur-al, and hard cheeses (like American, brie, andcheddar).

• Low-fat or nonfat yogurt, sour cream, andcream cheese instead of the high-fat varieties.

• Liquid vegetable oils that are high in unsatu-rated fat (these include canola, corn, olive, andsafflower oil).

• Margarine made with unsaturated liquid veg-etable oil as the first ingredient rather thanhydrogenated or partially hydrogenated oil.Choose tub or liquid margarine or vegetableoil spreads. The softer the margarine, themore unsaturated it is. If sodium intake needsto be controlled, try unsalted margarine. Use the food label to choose margarines withthe least amount of saturated fat.

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• Fewer commercially prepared and processedfoods (e.g., cakes, cookies, and crackers) madewith saturated or hydrogenated fats or oils.

• Foods high in starch and fiber such as wholewheat breads and cereals instead of foods highin saturated fats.

Reducing saturated fat intake will also help controldietary cholesterol since foods high in saturated fat areoften, but not always, high in cholesterol. Two addi-tional points for patients to remember when cutting backon dietary cholesterol are:

• Strictly limit organ meat (such as liver, brain,and kidney).

• Eat a total of two or fewer egg yolks a week (aswhole eggs or in prepared foods). Try substi-tuting two egg whites for each whole egg inrecipes, or using an egg substitute.

Foods high in starch and fiber are excellent substitutesfor high saturated fat foods. To help patients includemore foods high in starch and fiber, advise them tochoose:

• More vegetables and fruits. It is recommendedthat Americans eat 5 servings of fruits and veg-etables every day. They are low in saturated fatand total fat and have no cholesterol. Fruitsand vegetables are good sources of starch, fiber,vitamins, and minerals and are low in sodium.They are also low in calories (which helps withweight control) except for avocados and olives,which are high in both fat and calories. Manyfruits and vegetables are also high in antioxi-dants such as vitamin C, vitamin E, and beta-carotene. A diet high in these fruits and veg-etables may also help lower risk for heart dis-ease.

• Whole grain breads and cereals, pasta, rice,and dry peas and beans.

Patients should also be advised to use low-fat methods ofcooking:

• Bake, broil, microwave, poach, or roast insteadof breading and frying.

• When roasting, place the meat on a rack so thefat can drip away.

Physical Activity

Physical activity is important for all CHDpatients, whether they are overweight or not. To be effective, an exercise program should beindividualized with respect to the patient’s physical fitness, cardiac status, and desired formsof activity. Ongoing group exercise programssuch as cardiac rehabilitation, when available, are very conducive to adherence to increasedphysical activity, as is the support of an exercisecompanion.

Many CHD patients, especially those recoveringfrom an acute event, will need additional instruc-tion and monitoring when initiating a physicalactivity program. Cardiac rehabilitation pro-grams can meet this need by providing moni-tored exercise facilities, trainers, and instructionon life habit changes.

A physical activity program should be prescribedfor the CHD patient by the physician, takinginto account the patient’s cardiac status. Whenaerobic activity is appropriate, activities such asbrisk walking, jogging, swimming, bicycling,and tennis that place moderate stress on the car-diorespiratory system can be included. The pre-scription should include the amount, intensity,and frequency of desired activities. In CHDpatients, the intensity and duration of activityshould be increased gradually by the physicianover a few weeks or, in the case of obese or verysedentary patients, over several months and reg-ulated by their physician. Available data indi-cate that higher levels of activity will lead togreater rates of weight loss and greater degreesof LDL reduction and HDL increase.

Once an overweight patient has achieved thedesired body weight, it is most important that aregular exercise program be maintained perma-nently as caloric intake is liberalized. Thus, anaverage adult man weighing 150 pounds may beable to resume a 2,500-calorie diet after weightloss provided that a higher level of energy expen-diture is maintained. Experience has shown that weight loss is unlikely to be maintained inpersons who resume their original low level ofenergy expenditure.

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Although brisk walking for 20 to 30 minutesthree times a week can improve cardiorespiratoryfitness, this level of activity may be insufficient toprevent weight regain. Increased physical activitynevertheless is desirable in nonobese patientsbecause persons who maintain a moderately highlevel of physical activity are less likely to gainweight as they age and are therefore likely tomaintain lower levels of atherogenic lipoproteins,including LDL, and a higher HDL level.

Successful long-term reduction in CHD risk willdepend on the patient’s ability to integrate physi-cal activity into his or her life. Continued supportand encouragement of new behaviors, as well asacknowledgment of beneficial risk reductions, arepart of the physician’s role.

Weight Control

Weight reduction in overweight patients isextremely important for blood cholesterol control.Weight reduction even in small amounts canenhance the LDL-cholesterol lowering that can beachieved by reducing intakes of saturated fat andcholesterol. For example, 5 to 10 pounds ofweight loss can double the LDL-cholesterol reduc-tion achieved by reducing saturated fat and cho-lesterol. Both weight reduction and exercise notonly promote reduction of cholesterol levels buthave other benefits (see Figure 2). Thus, theyreduce risk for CHD in several ways in addition tolowering LDL-cholesterol levels.

A weight loss program slated for long-term suc-cess should include both calorie restriction andregular physical activity. The goal is to achieve arealistic weight loss rather than a marked reduc-tion of weight that cannot be sustained. Very-low-calorie diets (500 to 800 calories/day) are inef-fective for achieving long-term weight loss formost patients and are not recommended as thestandard approach to weight loss.

Weight reduction may be needed in more patientsthan are initially identified as being overweightfrom height-weight tables. This is particularlytrue for patients with predominant visceral obesitythat can be detected by a high waist-to-hip ratio.

Visceral obesity (“pot belly”) usually can be rec-ognized by visual inspection without the need forratio measurements.

A reasonable weight reduction plan for manypatients is one that reduces the typical caloricintake by 500 calories per day, although thereduction may vary according to the patient’sframe size. Caloric restriction should achieve agradual weight loss of 1/2 to 1 pound per week.If a patient is severely overweight, a greatercaloric restriction may be required, but as statedpreviously, very-low-calorie diets are not appro-priate for most patients. In addition to caloricrestriction, regular physical activity is often help-ful to achieve and especially to maintain weightloss.

Involvement of the patient in developing appro-priate behavior strategies is crucial for successfuldietary change and long-term adherence to therecommended diet. Techniques of behavior mod-ification have been helpful for promoting weightreduction, and may be instituted for overweightpatients. These techniques focus on unconsciouseating habits, compulsive behavior, binge eating,lack of resistance to social pressures for eating

Figure 2.

Physical WeightActivity Reduction

↓↓ Total cholesterol

↓ LDL-cholesterol

↑ HDL-cholesterol

↓ Triglycerides

↓ Blood pressure

↓ Risk for diabetes

↓Reduced risk for CHD

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cholesterol-raising foods, use of eating to relieveanxiety and depression, and lack of will power orself-control. The dietary counselor can explore allthese areas with the patient and guide him or herin overcoming these eating problems.

Diet Initiation, Monitoring, and Followup

In the outpatient setting, dietary therapy shouldbe initiated when the LDL-cholesterol level hasbeen confirmed to be above 100 mg/dL. At thetime of an acute MI, LDL levels frequently areabove 100 mg/dL, despite the fall in cholesterollevels caused by the acute event. If the LDL isabove 100 mg/dL, the period of hospitalization isa propitious time to begin the Step II diet.

On the Step II diet, a lipoprotein profile shouldbe obtained and adherence to the diet assessedafter about 6 weeks. If the goal LDL is notreached in 6 to 12 weeks, there is the option for the motivated patient to further reduce satu-rated and total fat intakes. If the goal LDL(≤100 mg/dL) is attained in 6 to 12 weeks, long-term monitoring can begin. The lipoprotein profile should then be repeated periodically (e.g.,every 3 to 6 months), depending on the observedstability of the patient’s LDL levels and cardiacstatus. If the LDL-cholesterol level remains 100 to 129 mg/dL after 6 to 12 weeks, the physician will have to exercise clinical judgmentto determine whether drug treatment should beconsidered.

Dietary therapy, including physical activity andweight control, should be continued even if drugs

are prescribed. The primary aim of dietary ther-apy is to reduce LDL-cholesterol levels, and itwill both enhance the LDL-lowering efficacy andminimize the dose of the prescribed medication.In addition, dietary modification and increasedphysical activity decrease CHD risk in otherways. Weight reduction and increased physicalactivity will reduce VLDL and raise HDL levels;weight reduction (combined with decreased saltand alcohol intake) will often lower blood pres-sure and improve glucose tolerance; and lowintakes of saturated fats and cholesterol probablyreduce the danger of acute coronary thromboge-nesis. Finally, a diet high in fruits, vegetables,grain products, and fish may supply substances(such as antioxidants) that protect against CHD.Thus, the broad range of mechanisms by whichdietary modification reduces risk for CHD makesit advisable to continue efforts to follow the rec-ommended diet and life habit changes even ifdrugs are prescribed.

Drug Treatment

When To Initiate Drug Treatment

Generally, drug treatment is indicated in patientswith established CHD if the stable baselineLDL-cholesterol level is 130 mg/dL or greater(Table 3). At these levels, LDL is not likely tofall to 100 mg/dL or less with dietary and lifehabit changes alone. If the baseline level is inthe range of 100 to 129 mg/dL, clinical judg-ment that weighs potential benefit, possible sideeffects, and costs must be used in the decision fordrug treatment.

Table 3. Drug Treatment in CHD Patients

LDL-Cholesterol Levels Diet and Life Habit Changes Drug Therapy

≤100 mg/dL Yes (LDL monitoring only annually) No

100–129 mg/dL Yes Clinical judgment

≥130 mg/dL Yes Yes

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CHD patients with LDL-cholesterol ≥130 mg/dLat the time of hospital discharge should be start-ed on cholesterol-lowering drug therapy becauseLDL levels are likely to rise as patients becomemetabolically stable.

Drug Selection

Selection of an appropriate cholesterol-loweringmedication for the CHD patient is often impor-tant to achieve adequate LDL reduction to reachthe goal of 100 mg/dL. The major drugs pre-scribed for this purpose are statins, bile acidsequestrants, and nicotinic acid. Based on thepositive results of clinical trials with statins,including 4S, CARE, and Post CABG, and thelarge degree of LDL-cholesterol lowering pro-duced by these agents, statins are considered thedrug of choice to lower LDL-cholesterol inpatients with CHD. Bile acid sequestrants andnicotinic acid are also used, often as part of combination therapy (see Combination DrugTherapy, page 16). Nicotinic acid is useful forraising low HDL levels, a problem frequentlyencountered in CHD patients. Gemfibrozil can

also be used in combination with statins in select-ed patients with combined elevations of choles-terol and triglycerides. Reproducible patienthandout sheets for statins, bile acid sequestrants,and nicotinic acid are provided on pages 22 to 26.

StatinsAs a drug class, statins (the short-hand term forHMG CoA reductase inhibitors) produce thegreatest LDL-cholesterol lowering (Table 4).There are currently five statins on the market inthe United States: lovastatin, pravastatin, sim-vastatin, fluvastatin, and atorvastatin. Statins areused in patients who require significant reductionof their LDL-cholesterol levels. These drugslower cholesterol by inhibiting HMG-CoA reduc-tase, a key rate-limiting enzyme in the pathwayfor cholesterol biosynthesis. To meet the intracel-lular requirements for cholesterol in the face ofthis inhibition of cholesterol synthesis, LDLreceptor function is upregulated, primarily in theliver, thereby lowering serum LDL-cholesterollevels. Treatment with statins in the 4S, CARE,and Post CABG studies produced large reduc-

Table 4. Summary of Statins (HMG CoA Reductase Inhibitors)

Available drugs Lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin

Major use To lower LDL-cholesterol

Lipid/lipoprotein effects LDL-cholesterol: ↓ 20–60 percent

HDL-cholesterol: ↑ 5–15 percent

Triglycerides: ↓ 10–40 percent

Contraindications Active or chronic liver disease

Use with caution Concomitant use of cyclosporine, gemfibrozil, or niacin—increasedrisk of myopathy

Reduce CHD risk Yes

Long-term safety Evidence from about 10 years of extensive clinical use and in 5-year controlled trials

Major side/adverse effects Elevated hepatic transaminase, myopathy, upper and lower gastrointestinal complaints

Statin + anticoagulant may increase prothrombin time

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tions in LDL-cholesterol levels and significantbenefits in terms of reduced nonfatal MIs andCHD deaths (4S, CARE), reduced total mortality(4S), decreased need for revascularization (4S,CARE, Post CABG), and decreased progressionof atherosclerosis in grafted vessels (Post CABG).

The statins are usually given in a single dailydose and should be taken with the evening mealor at bedtime to maximize LDL reduction. Thestatins are well tolerated by most patients.Occasionally patients have gastrointestinal sideeffects including dyspepsia, flatus, constipation,and abdominal cramps. These symptoms usuallyare mild to moderate and generally subside astherapy continues. Infrequent side effects includeelevated transaminases and myopathy. Elevatedhepatic transaminases occur in approximately 1 percent or less of cases. Myopathy occurs inabout 0.1 percent of cases; its frequency isincreased when statins are given withcyclosporine, gemfibrozil, or nicotinic acid.Myopathy is rapidly reversible if diagnosed earlyand treated with discontinuance of drug andhydration, but if the drug is not discontinued,severe myopathy (rhabdomyolysis) can progressto myoglobinuria and acute renal failure. Allpatients started on statins should be instructed to

report muscle discomfort and weakness or brownurine immediately, and a creatine kinase mea-surement should be done to check for myopathy.

Bile Acid Sequestrants Bile acid sequestrants (also called resins) (Table 5)bind with cholesterol-containing bile acids in theintestinal lumen, interrupting the enterohepaticcirculation of bile acids and promoting conver-sion of cholesterol into bile acids in the liver.Reduction of liver cholesterol content stimulatesthe formation of LDL receptors, which enhancesLDL removal from the circulation and lowersserum LDL levels. The major effect of bile acidsequestrants is to lower LDL-cholesterol by about10 to 20 percent. In some patients, bile acidsequestrants may increase serum triglycerides.Experience with the sequestrants indicates thattheir long-term use is safe. These drugs are notabsorbed from the gastrointestinal tract and lacksystemic toxicity. Bile acid sequestrants are use-ful in patients with moderately elevated LDL-cholesterol levels. Bile acid sequestrants are alsohighly effective when used in combination withstatins for more marked LDL reduction as aresult of their additive mechanisms.

Table 5. Summary of Bile Acid Sequestrants

Available drugs Cholestyramine, colestipol

Major use To lower LDL-cholesterol

Lipid/lipoprotein effects LDL-cholesterol: ↓ 10–20 percent

HDL-cholesterol: ↑ 3–5 percent

Triglycerides: may increase, or no effect

Contraindications Familial dysbetalipoproteinemia

Triglycerides >500 mg/dL

Use with caution Triglycerides >200 mg/dL

Reduce CHD risk Yes

Long-term safety Yes

Major side/adverse effects Upper and lower gastrointestinal complaints

Decrease absorption of other drugs

Pancreatitis in patients with hypertriglyceridemia

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Cholestyramine and colestipol, the two main bileacid sequestrants, are available as powders ortablets. Bile acid sequestrant powders must bemixed with water or fruit juice and taken once or twice (rarely three times) daily with meals.Tablets must be taken with large amounts of fluids to avoid gastrointestinal symptoms.Sequestrant therapy may produce a variety ofsymptoms, including constipation, bloating, epigastric fullness, nausea, and flatus.

Although sequestrants are not absorbed, theymay interfere with the absorption of other medi-cines if taken at the same time. Therefore, othermedications should be taken at least 1 hourbefore or 4 to 6 hours after the sequestrant.

Nicotinic AcidNicotinic acid (niacin) (Table 6) is a water-solubleB vitamin that can produce favorable effects onall lipids and lipoproteins when given in doseswell above the vitamin requirements. Nicotinicacid lowers LDL-cholesterol levels by 10 to 25percent and triglycerides by 20 to 50 percent,while raising HDL-cholesterol levels by 15 to 35percent. It can also lower lipoprotein(a) levels,up to 30 percent in some cases. Niacin has been

shown to lower the rate of recurrent MI in CHDpatients in the Coronary Drug Project; the treat-ed group also had reduced total mortality in a15-year followup of that study. All patients tak-ing nicotinic acid to lower serum cholesterolshould be closely monitored by trained healthprofessionals to avoid complications from drugtoxicity.

Nicotinic acid therapy is especially useful inpatients with moderately elevated LDL-choles-terol, elevated triglycerides, and low HDL-cho-lesterol. Patients on nicotinic acid are usuallystarted on low daily doses (e.g., 125 mg twicedaily) and gradually increased to an average dailydose of 1.5 to 3 g per day (crystalline form).

The most common side effect of nicotinic acid isflushing. Most patients develop a tolerance toflushing, and in some patients, it can bedecreased by taking the drug during or aftermeals or by taking aspirin or a nonsteroidal anti-inflammatory drug (NSAID). A variety of gas-trointestinal symptoms, including nausea, indi-gestion, flatus, vomiting, diarrhea, and the acti-vation of peptic ulcers, have been seen with theuse of nicotinic acid. Other major adverse effectsinclude hepatotoxicity, hyperuricemia and gout,

Table 6. Summary of Nicotinic Acid

Available drugs Crystalline nicotinic acid

Sustained-release (or slow-release) nicotinic acid (not FDA-approved)

Major use Useful in most lipid and lipoprotein abnormalities

Lipid/lipoprotein effects LDL-cholesterol: ↓ 10–25 percent

HDL-cholesterol: ↑ 15–35 percent

Triglycerides: ↓ 20–50 percent

Contraindications Chronic liver disease

Use with caution Non-insulin-dependent diabetes mellitus, gout, or hyperuricemia

Reduce CHD risk Yes

Long-term safety Yes for crystalline form; uncertain for sustained-release form

Major side/adverse effects Flushing, hepatotoxicity (especially for sustained-release form),hyperglycemia, hyperuricemia or gout, and upper gastrointestinalcomplaints

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and hyperglycemia. Risk of these effects increas-es as the dose of nicotinic acid is increased. Rareside effects are toxic amblyopia, acanthosis nigri-cans, and myopathy.

FibratesThe cholesterol-lowering drugs called fibrates(fibric acid derivatives) are used primarily inpatients with high triglyceride levels.Gemfibrozil is the fibrate most commonly used inthe United States. Fibrates are primarily effec-tive in lowering triglycerides and, to a lesserextent, in increasing HDL-cholesterol levels.Gemfibrozil is not recommended by the Foodand Drug Administration as single drug therapyfor patients with CHD.

Fibrates are usually given in two daily doses 30 minutes before the morning and eveningmeals. The reductions in triglycerides generallyare in the range of 20 to 50 percent, withincreases in HDL-cholesterol of 10 to 15 percent.Gemfibrozil generally reduces LDL-cholesterol by10 to 15 percent in patients whose only abnor-mality is elevated LDL; however, LDL-cholesterolmay be increased in patients with elevatedtriglycerides.

Fibrates are generally well tolerated by mostpatients. Gastrointestinal complaints are themost common side effects. Fibrates increase thelithogenicity of bile, which increases the likeli-hood of developing gallstones. Fibrates canpotentiate the effect of anticoagulants. The addi-tion of gemfibrozil to statin therapy increases therisk of myopathy; this combination should there-fore be used only in selected patients with com-bined hyperlipidemia. Patients must be alertedto the increased risk of severe myopathy.

Hormone Replacement TherapyThe risk of CHD is increased in postmenopausalwomen, whether the menopause is natural, surgi-cal, or premature. This increasing risk may berelated to the loss of estrogens after menopause.Hormone replacement therapy (HRT) may beprescribed when women begin to experiencesymptoms from menopause.

There is currently no clinical trial evidence proving conclusively that CHD event rates arereduced through the use of HRT. The Post-menopausal Estrogen/Progestin Interventions(PEPI) Trial looked at the effect HRT has onCHD risk factors. Results from the PEPI studyshowed that:

• Estrogen-only therapy raised the level ofHDL-cholesterol.

• Combined estrogen-progestin therapies alsoincreased HDL levels, although less thanestrogen alone.

• All the hormone regimens decreased the levelof LDL-cholesterol about the same.

• Fibrinogen levels were decreased by all thehormones, which may be a desirable change.

• None of the hormone regimens caused a sig-nificant weight gain.

• All the hormone regimens caused some rise intriglyceride levels.

The beneficial effect of HRT on lipid levels (15 percent LDL reduction) would favor its use inmany women with CHD. If LDL is elevatedslightly above the 100 mg/dL goal, HRT can beconsidered an appropriate lipid-lowering therapyin postmenopausal women with CHD. If HRTdoes not enable the patient to reach her goal, orif LDL-cholesterol levels are moderately elevatedat baseline, HRT may be combined with othercholesterol-lowering drugs to reach the LDL goalof 100 mg/dL or less.

Combination Drug TherapyIn most patients with CHD, therapy with a sin-gle drug in conjunction with diet therapy shouldbe adequate. In many patients with only modestelevations of LDL-cholesterol, low doses of drugcombined with diet therapy will suffice; however,greater elevations of LDL require more intensivedrug treatment. It is important to use doses of statins adequate to reach the LDL target of100 mg/dL. If the goal of therapy is not attainedafter 3 months with single drug therapy, howev-er, consideration can be given to adding a second

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agent (see Table 7). The decision to proceed withmore aggressive combination drug therapy inCHD patients must be made after counseling thepatient about potential side effects. These draw-backs, however, may be more than offset byregression or slowed progression of atherosclerosisand reduction in cardiovascular events and mor-tality. In addition, it may be possible to avoidsome of the drawbacks of combination therapyby using low doses of each drug.

Some patients with marked elevations of LDL-cholesterol, especially those with severe forms ofhypercholesterolemia, may not achieve LDL-cho-lesterol levels of 100 mg/dL or less, even whendiet therapy is combined with combination drugtherapy. Even so, clinical trials indicate that amajor reduction in CHD risk occurs when thereis a substantial LDL-cholesterol reduction (30 to40 percent), even if the target goal of 100 mg/dLor less is not reached. Thus, aggressive LDL-cho-lesterol lowering should be pursued in all CHDpatients with elevated levels of LDL-cholesterol.

Combination of a bile acid sequestrant witheither nicotinic acid or a statin has the potentialof lowering LDL-cholesterol levels by 40 to 50percent or more. For most patients, the judicioususe of one or two drugs should provide an ade-quate LDL-cholesterol-lowering effect. Most

cholesterol-lowering drugs can be used in combi-nation. Nonetheless, a statin plus fibrate carriesan increased risk of myopathy, whereas a statinplus nicotinic acid may increase the likelihood ofhepatotoxicity, and possibly myopathy.

Monitoring and Followup

With good drug adherence, maximum lowering of LDL-cholesterol is achieved at any given doseof lipid-lowering medication within 4 to 6 weeksof initiating or changing therapy. Followup LDLdetermination and assessment of possible adversebiochemical changes should be made 6 to 8weeks after initiating or changing drug therapy.Nicotinic acid is an exception to this guideline;repeat measurements should be made when thenicotinic acid dose has been stable for 4 to 6weeks (e.g., 1,500 mg per day plateau).

After the target LDL-cholesterol concentrationhas been achieved, patients should be followed at2- to 3-month intervals through the first year. Ifthe target LDL-cholesterol is not achieved withthe initial dose, then drug titration should beused to find the optimum dose. Drugs that mustbe titrated to maximum efficacy are the statins,nicotinic acid, and the bile acid sequestrants.Gemfibrozil is prescribed in a single dosageschedule.

Table 7. Drug Selection for Combination Therapy

Lipid Levels Single Drug Combination Drug

Elevated LDL-cholesterol and Statin Statin + BAS

triglycerides <200 mg/dL Nicotinic acid (NA) Statin + NA*

Bile acid sequestrant (BAS) NA + BAS

Elevated LDL-cholesterol and Statin Statin + NA*

triglycerides 200–400 mg/dL Nicotinic acid Statin + Gemfibrozil†

NA + BAS

NA + Gemfibrozil

* Possible increased risk of myopathy and hepatitis.

† Increased risk of myopathy. Must be used with caution.

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After 1 year of therapy during which theresponse has been established and there is no evi-dence of biochemical toxicity, patients may havetheir lipid levels monitored at 4- to 6-monthintervals; more frequent followup may be dictat-ed by their cardiac status. Measurements tocheck for toxicity should be obtained at the sametime as assessment of lipid and lipoprotein levels.When placing patients on cholesterol-loweringtherapy, as with any drug, it is important thatpatients be asked to report any side effects theyexperience.

Patients should be advised that an elevated cho-lesterol, like many other disorders, is not curedbut is only controlled by diet and drug therapy.Discontinuation of treatment is quickly followedby a rise of the cholesterol and a return of theCHD risk to the high level that existed beforetherapy was started.

ADHERENCE

Cholesterol reduction in CHD patients is highlyeffective in reducing CHD events—but it has tobe maintained. The challenge is to combine theefforts of professionals with those of patients andtheir families to maximize the likelihood thatcholesterol-lowering treatment will be properlyinitiated and adhered to. Primary care physi-cians, cardiovascular specialists, nurses, registereddietitians, and pharmacists need to work as ateam to maximize the quality of patient care andthe likelihood that patients will follow the treat-ment regimen.

Role of the Physician

Cholesterol lowering should be an integral part ofthe routine management of CHD—no less sothan aspirin and beta-blockers, whose capacity toreduce the risk of recurrent CHD events isequaled by cholesterol lowering. Primary carephysicians will often be the ones to identify theneed to lower the CHD patient’s cholesterol levelin an outpatient setting. They will therefore beresponsible for initiating cholesterol-lowering

therapy and, if necessary, providing a referral to acardiovascular specialist, and possibly a dietitian,for help in managing coronary disease.

Cardiovascular specialists will probably be theones who are responsible for the identificationand treatment of an elevated blood cholesterol inCHD patients suffering an acute event. The hos-pital stay provides a good opportunity to starttreatment. At discharge, if LDL-cholesterol is130 mg/dL or higher, diet/lifestyle therapytogether with drug treatment should be initiated.For patients with LDL-cholesterol between 100and 129 mg/dL, diet should be initiated and theLDL-cholesterol remeasured in 6 weeks.Cholesterol-lowering therapy after dischargeshould be a coordinated effort between the car-diovascular specialist, the primary care physician,and the patient.

A key aspect in the coordination of cholesterol-lowering therapy is the communication betweenthe physician and the patient. Key topics thatneed to be addressed at the outset include:

• Rationale for treatment

— Appraisal and significance of the lipidabnormality

— Potential benefits of treatment

— Goals of treatment

— Treatment plan

• Step II diet

— Plan for adoption and maintenance ofthe diet

— Key dietary changes to be made

— Nutrition professionals available forassistance

• Other life habit changes

— Prescription for physical activity and, ifnecessary, weight loss

• Drug treatment

— Whether drug therapy is in the picturenow, or possibly later

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These topics and others are covered in an easy-to-digest manner in the National CholesterolEducation Program patient booklet, LiveHealthier, Live Longer: Lowering Cholesterol for thePerson With Heart Disease. Giving your patient acopy of the booklet will help him or her getstarted on cholesterol-lowering treatment andwill support long-term adherence as well (seeorder form on page 31).

During long-term followup visits, routineinquiries about the patient’s adherence to thetreatment program help reinforce the importancegiven it by the physician. In addition, respond-ing to the patient’s questions and concerns canhelp overcome barriers to long-term adherence tothe treatment regimen.

Role of the Nurse

The patient’s long-term success in controllingcholesterol can be greatly enhanced by involve-ment of the office, clinic, or home health carenurse. Nurses are health professionals trained toprovide health education and interpret healthbehavior. Particularly important is the nurse’srole in reinforcing and interpreting the instruc-tions provided by the physician. In addition, thenurse can provide detailed instruction on practi-cal approaches to adherence. Nurses are also ableto provide support to patients who are followinglong-term treatment programs by discussingproblems and challenges that are encountered.

Role of the Registered Dietitian

The registered dietitian or other qualified nutri-tion professional is particularly important topatients with CHD for ensuring nutritional ade-quacy and balance on the Step II diet. Dietitianswith particular expertise in cholesterol manage-ment are available in most large medical centerswhere they are often part of a multidisciplinarylipid clinic or cardiac rehabilitation team. Theycan also be identified through the AmericanDietetic Association referral hotline (800-877-1600). Dietitians are best equipped to interpret

the patient’s nutritional habits and to offerdetailed, practical instructions on carrying outdietary treatment programs, such as how to shopfor groceries, prepare tasty low-saturated-fatfoods at home, select foods from restaurantmenus, and follow the prescribed diet when traveling.

Role of the Pharmacist

The community or clinic pharmacist can alsoplay an important role in promoting long-termcholesterol control, particularly for patients withcholesterol levels that require cholesterol-lower-ing drug therapy. These professionals often havethe greatest contact with the patient who isundergoing long-term treatment and are readilyaccessible in most communities. Their interac-tion with the patient should begin with thepatient’s first prescription for cholesterol-lower-ing therapy and continue as the patient returnsperiodically for prescription refills. The pharma-cist has the opportunity to reinforce and extendinstructions to the patient about how, why, andwhen to take the prescribed medication. Thepharmacist can also provide support to patientson long-term therapy by advising how to overcome side effects and other problems thatmay interfere with adherence to the treatmentprogram.

By working as a team, health professionals canprovide a consistent message that reinforces posi-tive health behaviors. This message will supportlong-term adherence to both lifestyle changesand drug therapy, thereby promoting the mosteffective treatment of the patient’s CHD risk.

Strategies To Enhance Adherence

To be maximally effective in achieving long-termcholesterol control, each health professionalinvolved in the patient’s care should be aware ofand effectively utilize techniques that have beenshown to be effective in enhancing adherence totreatment regimens. Following is a summary ofsome of these strategies.

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• Teach the patient the treatment regimen.

Diet/lifestyle therapy

– Provide patients with practical ways tocut back on saturated fat, total fat, andcholesterol.

– Provide patients with a referral to adietitian or other qualified nutritionist.

– Instruct patients on the benefits ofphysical activity and provide them witha personalized exercise prescription.

– Provide realistic goals for weight controland maintenance.

Drug treatment

– Teach patients how to take their med-ication.

– Teach patients to recognize and manageside effects.

– Teach patients to manage missed doses.

– Make sure patients know how to con-tact someone if they need assistance.

• Give patients a copy of Live Healthier, LiveLonger: Lowering Cholesterol for the Person WithHeart Disease (see order form on page 31). Itprovides valuable assistance in teachingpatients the treatment regimen and encourag-ing long-term adherence.

• Help the patient identify ways to remembermedication doses. For example:

– Tie doses to daily rituals, such as coincid-ing doses with meals.

– Set alarm clocks or watches to signal dosingtimes.

– Place reminder cards in prominent places inthe home.

– Have spouses or friends remind them ofdoses.

– Send reminders of appointments and med-ication refills.

– Use a daily medication box or blister pack-aging to organize and prompt drug doses.

• Develop reinforcers of adherence.

– Encourage patients to follow the progress oftheir therapy by keeping logs of cholesterollevels and other clinical markers (see exam-ple below).

– Review patient logs periodically to reinforceadherence.

– Reward positive treatment outcomes—e.g.,praise the patient for good control.

• Anticipate common problems and teachpatients how to manage them. Poor adherencemay occur because the patient lacks knowledgeabout what to expect from medications andwhat to do if unexpected events occur.

– Teach patients about common side effects oftheir medication and how to minimize andmanage them.

– Teach patients to identify and interpretsymptoms.

– Teach patients how to initiate self-treatmentif appropriate.

– Teach patients when to call for help.

Cholesterol-Monitoring Log

Medication LDL- Total HDL-Date Name Dose Cholesterol Cholesterol Cholesterol Triglycerides

• Provide ongoing education and updates aboutthe patient’s illness and treatment. Provideupdates about the patient’s therapy as newinformation becomes available and as theirlevel of understanding increases.

SUMMING UP

Cholesterol lowering in CHD patients ishighly effective in reducing the risk for MIand death from CHD. There is almost notreatment that offers CHD patients morebenefit in reducing CHD risk. Cholesterollowering should therefore be as routine apart of CHD management as aspirin.Careful attention to initiating appropriatecholesterol-lowering therapy and sustainingit will improve the health and prolong thelives of millions of Americans who haveCHD.

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• Involve a spouse, family member, or friend inthe patient’s therapy program. One of thestrongest influences on adherence is a familymember or close friend. Involve someonewho is close to the patient when providing theinitial instructions (with the patient’s permis-sion) and encourage the individual to supportthe patient’s long-term treatment program.

• Establish a supportive relationship with thepatient. Patients are more likely to adhere totreatment regimens if they like their healthprofessionals, trust their advice, and perceive acaring attitude. Listening carefully to thepatient’s questions, concerns, fears, and mis-conceptions about illnesses and treatmentscan facilitate effective counseling.

• Make adherence important by asking aboutit. Periodically asking about adherence helpsunderscore the importance placed on it by thehealth professional, but care should be takento encourage rather than blame the patient.

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Take Your Statin Regularly

To get the full reduction in cholesterol levels, it isimportant to take your entire dose each day. Donot take more than this in any one day. If youshould forget to take a dose until the next day,skip it. Do not try and catch up with misseddoses; instead, continue with the next scheduleddose.

Side Effects

Most people do not experience serious side effectsfrom statins. Occasionally patients have mild tomoderate side effects such as upset stomach, gas,or constipation. These symptoms usually go awayas the body gets used to the new medication.

Infrequently, there may be a problem with liverenzyme changes. Even less often there may bemuscle problems. If you have muscle pain orweakness or brown urine, you should call thenumber below immediately. You will need ablood test to find out if you are really having amuscle problem, and if so, you will need to stopthe medication.

Side effects are more likely to appear when youfirst start taking statins and just after increasingthe daily dose. If you should notice any sideeffects with your new medicine, please call ouroffice at the number below.

While taking this medication, you will need rou-tine blood tests to monitor the effect of the med-ication on liver function and cholesterol levels. Itis extremely important to obtain these blood testsas scheduled.

PATIENT HANDOUT

Patient Instructions for Taking Statins

Statins are also known as “HMG CoA reductaseinhibitors,” because they block the action of anenzyme or chemical substance called “HMG CoAreductase” that is important in cholesterol pro-duction in the body. The statins currentlyinclude lovastatin, pravastatin, simvastatin, fluva-statin, and atorvastatin. These prescription med-ications are extremely effective in lowering bloodcholesterol levels and lowering the risk of heartattack. They have been used safely for about 10years by patients with elevated blood cholesterol.The primary benefit of statins is their ability tolower LDL-cholesterol (which some people callthe “bad” cholesterol). Your starting dose of__________ will be _____milligrams daily.This dose will be adjusted based on your choles-terol levels at future visits. To obtain the bestresults with your statin medication, follow theinstructions below.

Taking Statins

Statins work best if they are taken in the eveningbecause this is when the body makes the mostcholesterol. You should also try and take yourstatin medication when you have food in yourstomach. It may be most convenient to takeyour statin with or just after your dinner (supper)or your bedtime snack.

Questions

If you have any questions or problems while taking your statin, please call us during the day at_________________________________ or at night at ______________________________________.

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the beverage to wash down any powderremaining in your mouth. To reduce sideeffects, drink at least 2 to 6 ounces of fluid per packet/scoop of resin powder you take.

You can drink your medication immediately, oryou can mix larger doses and store refrigeratedfor up to 2 days. Many patients find thatmixing their medications with fluids inadvance allows time for the beads of medica-tion to swell and have a less “gritty” taste andfeel.

b. You may also mix the contents of the packetor scoop of powder in a highly fluid food orfruit. Examples include applesauce, soup, andpulpy fruits such as crushed pineapple, pears,peaches, or fruit cocktail.

To mix the powder with food, pour the con-tents of a packet or scoop into a bowl, add atleast 6 ounces of the food chosen, mix it well,and eat.

Dose of Resin

The dose of resin that will produce the greatestlowering of blood cholesterol levels is betweenfour and six scoops or packets of powder dailymixed with a beverage. You will need to help usdetermine the dose that works best for you with-out causing unpleasant side effects. To do this,start by taking only one packet or scoop of pow-der daily with dinner (supper). If you are able totake this dose without problems for a week ortwo, increase your dose to two packets or scoopsof powder, one with breakfast and one with din-ner. After you have successfully taken this dosefor 1 or 2 weeks, increase your dose to threepackets or scoops of powder each day. Continuewith this plan until you have arrived at the bestdose for you. Although six doses per day is ideal,we will be content with whatever dose you cancomfortably take each day, especially if it pro-duces a good cholesterol-lowering effect. Mostpatients take between two and four doses perday.

PATIENT HANDOUT

Patient Instructions for Taking ResinTherapy

You have been given one of the following med-ications to lower your blood cholesterol level:colestipol or cholestyramine. These medicationsare generally referred to as bile acid sequestrants,bile acid resins, or simply resins. Resins lowerblood cholesterol levels by binding bile acids inthe intestines and causing more of the cholesterolin the bloodstream to be converted into bile acidsand eliminated from the body through the stool.To get the best results with resin therapy, followthe instructions below.

Preparing Your Resin

Your doctor will prescribe either resin powder ortablets. Resin tablets do not need to be pre-pared, but must be taken with large amounts offluid.

If your doctor prescribes resin powder, you mustmix it in a beverage or other fluid before youtake it (see below for instructions). NEVER takethis medicine in its dry form, as it may cause youto choke.

a. Mix the contents of a packet or scoop of pow-der with your choice of beverage. We recom-mend noncarbonated beverages such as juices,milk, or just water. Carbonated beveragesmay cause air to be entrapped, which couldcause belching. You may experiment with dif-ferent beverages until you find the one youlike.

To mix your powder with a beverage, pour itinto a cup or glass. Add two or more ouncesof the beverage you have chosen, stir it vigor-ously (some people use a mixer for this), anddrink. Note that the powder will not totallydissolve in the liquid but should be suspendedby the stirring and thus be easier to drink.You may follow this with a swallow or two of

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Times To Take Your Dose of Resin

Take the dose of powder mixed with a beveragejust before or with meals. If you choose to takeonly one dose each day, take it with the heaviestmeal (usually dinner or supper for most people).If you choose to take it twice daily, take it withthe two heaviest meals or with the most conve-nient meals. This is usually breakfast and dinner(supper). When you increase your dose to threepackets or scoops of powder per day, you maytake one dose three times a day with each meal,instead of once or twice daily, if you prefer.

If you are taking other medications, please check on theexact time to take the resins because they may interferewith absorption of other medications from the intestines.As a general rule, you should take your other medica-tions 1 hour before or 6 hours after you take your resin.

Take Resin Regularly

To achieve the best effects from the medication, itis very important to consistently take the samenumber of doses of medication each day. If youforget the morning dose, take it with lunch. Ifyou forget the dinner dose, take it later in the

evening with a light snack. If you should forgetyour dose until the next day, do not try to catchup with the missed doses; instead, continue withthe next scheduled dose.

Side Effects

Resins are not absorbed into the bloodstream,but pass directly through the gastrointestinaltract, binding with bile acids and cholesterolalong the way and eliminating them with thestools. If side effects occur, they will be limitedto the stomach and intestines and will occur dur-ing the early days of therapy. Some symptomsassociated with these medications include consti-pation, bloating, gas, and heartburn.Constipation may be relieved by increasing fluidand dietary fiber or by commercial products con-taining fiber, such as psyllium. Bloating or gasmay be relieved by trying to avoid swallowing airwhen taking the resin mixture. Once the bodyhas gotten used to the medication, side effectsymptoms (if they occur at all) will lessen. Pleasecall us if you experience any discomfort whiletaking this medication so that we can advise youof ways to lessen them.

Questions

If you have any questions or problems while taking your resin, please call us during the day at_________________________________ or at night at ______________________________________.

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Dose of Niacin

The dose of niacin must be carefully adjusted ineach patient to effectively lower blood cholesterollevels and to minimize side effects. Generally,total daily doses between 1,500 milligrams (mg)and 3,000 mg are required. However, youshould slowly work up to this dose level. Oneschedule for doing this is presented below. Ifyou are having side effects, go slower.

First week: 125 mg twice daily

Second week: 250 mg twice daily

Third week: 500 mg twice daily

Fourth week: 750 mg twice daily

Fifth week: 1,000 mg twice daily

Sixth week: 1,500 mg twice daily

We will inform you when you should makeanother clinic visit. We would like to see you 4 to 6 weeks after you have attained a total dailydose of ________ mg of niacin.

Taking Niacin

Before taking a dose of niacin, FIRST take oneadult aspirin tablet (325 mg) or a dose of thenonprescription medication ibuprofen 30 min-utes before your morning dose of niacin.Enteric-coated aspirin is preferred because it isless bothersome to the stomach. Repeat thisevery morning for the first 14 days when youfirst begin niacin therapy or each time youincrease your daily dose.

a. Taking aspirin or ibuprofen will reduce anyflushing, warm feeling, tingling, or headachesymptoms that niacin may cause. Thesesymptoms may occur when first beginningniacin therapy. They are not harmful and areto be expected with this medication. Thesymptoms occur because niacin increases theflow of blood throughout the body by dilating(widening) blood vessels. The aspirin oribuprofen will reduce this effect without

PATIENT HANDOUT

Patient Instructions for Taking NicotinicAcid (Niacin)

Niacin or nicotinic acid is a B vitamin that effec-tively lowers blood cholesterol levels. It hasbeen used safely for several decades by patientswith high blood cholesterol. It has the advan-tage of not only lowering total cholesterol andLDL-cholesterol (which some people call the“bad” cholesterol) but also lowering triglyceridesand raising HDL-cholesterol (which some peoplecall the “good” cholesterol). It has been used inmajor studies of cholesterol-lowering therapy,which show that it is associated with a decreasedrisk of heart attacks and a reduction in thebuildup of atherosclerosis (plaque) in coronaryblood vessels.

Follow the instructions below to obtain the besteffects with niacin.

Dosage Forms of Niacin

Niacin or nicotinic acid is available in two forms.Both forms lower the blood cholesterol, butthere are important differences you should knowabout.

• Immediate release. A tablet or capsule thatwill dissolve in your stomach within minutesafter you swallow it and release niacin quicklyinto your bloodstream.

• Extended release. This form may produce lessflushing, but it is not recommended for rou-tine use because of increased risk of liverproblems. This form is not approved by FDAfor treatment of cholesterol disorders.

Nicotinamide is sometimes referred to as niacin,but it does not lower cholesterol. Please try topurchase the same brand of niacin each time. Ifyou should change brands, please notify yourdoctor’s office. To ensure that you have chosenthe appropriate form of niacin, check with yourpharmacist.

26

lessening niacin’s effect on cholesterol. Intime, the body should develop a tolerance tothese symptoms to the point that they are nolonger bothersome.

b. Note that each time niacin therapy is stopped,these symptoms may reappear when it isrestarted. Also, these symptoms may appeareach time the dose of niacin is increased.Thus, be sure to take one aspirin or ibuprofendose every day for several days each timeniacin is restarted or the dose is increased.

c. Try to take niacin when you have food in yourstomach. It may be most convenient to take adose with or just after breakfast (or lunch) andwith or just after dinner (supper). This willreduce any nausea, gas, or heartburn symp-toms that niacin may cause. If these symp-toms occur at all, they are more likely to occursoon after starting niacin. They probablyoccur because niacin is a weak acid and mayirritate the stomach. Taking niacin with foodshould help buffer the acid and reduce thesesymptoms.

Take Niacin Regularly

To have the best reduction in cholesterol levelsand particularly to avoid side effects, it is VERYimportant to take your entire dose of niacin eachday. Do not take more than this in any one day.If you should forget your morning dose, take itlater in the evening with a light snack. If you donot remember that you missed a dose until thenext day, skip it. Do not try to catch up withmissed doses, as they may increase side effectsymptoms. Some patients may find it easier totake three doses of niacin a day.

Side Effects

As pointed out, tingling, warm feelings,headaches, nausea, gas, and heartburn may occurwith niacin. In addition, niacin may cause diar-rhea, fatigue, itching, or a rash. Like the othersymptoms, these are not harmful, but may bebothersome. Also, like the other symptoms, theywill lessen once the body has gotten used to themedication. Itching and the rash may be causedby an increased flow of blood throughout thebody and may also be reduced with the dose ofaspirin or ibuprofen taken along with niacin.

In general, side effect symptoms are more likelyto appear just after you first start taking niacinand just after increasing the daily dose. Takingaspirin or ibuprofen daily and taking niacin doseswith food should reduce these symptoms. Asyou continue to take niacin, you should noticethat these symptoms will diminish or disappear.

If side effect symptoms are intolerable, reduceyour total daily dose by one tablet or capsule.For example, if you are taking two capsules twicea day with breakfast and dinner, reduce yourdose to one capsule with breakfast and two cap-sules with dinner (or one capsule three times aday with each meal). Once your body adjustsand the symptoms have disappeared, increaseyour dose back to two capsules twice daily. Ifthese symptoms continue to be a problem, pleasecall your doctor.

While taking this medication, you will also needroutine blood tests to be sure that other sideeffects are not occurring. These blood tests mayinclude tests of liver function, glucose, and uricacid. It is extremely important to obtain these asscheduled.

Questions

If you have any questions or problems while taking your niacin, please call us during the day at_________________________________ or at night at ______________________________________.

27

REFERENCES

1. National Cholesterol Education Program ExpertPanel. Second report of the expert panel on detection,evaluation, and treatment of high blood cholesterol inadults (Adult Treatment Panel II). Washington, DC:U.S. Department of Health and Human Services,Public Health Service, National Institutes ofHealth, National Heart, Lung, and BloodInstitute; 1993. NIH Publication No. 93-3095.

2. Scandinavian Simvastatin Survival Study Group.Randomised trial of cholesterol lowering in 4444patients with coronary heart disease: theScandinavian Simvastatin Survival Study (4S).Lancet 1994;344:1383–89.

3. Sacks FM, Pfeffer MA, Moye LA, et al. The effectof pravastatin on coronary events after myocardialinfarction in patients with average cholesterol lev-els. N Engl J Med 1996;335:1001–9.

4. The Post Coronary Artery Bypass Graft TrialInvestigators. The effect of aggressive lowering oflow-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes insaphenous-vein coronary-artery bypass grafts. N Engl J Med 1997;336:153–62.

5. Rossouw JE, Lewis B, Rifkind BM. The value oflowering cholesterol after myocardial infarction.N Engl J Med 1990;323:1112–9.

6. Rossouw JE. Clinical trials of lipid-loweringdrugs. In: Rifkind BM, ed. Drug treatment ofhyperlipidemia. New York: Marcel Dekker, Inc.;1991:67–88.

7. Research Committee. Low-fat diet in myocardialinfarction: a controlled trial. Lancet 1965;2:501–4.

8. Research Committee to the Medical ResearchCouncil. Controlled trial of soya-bean oil inmyocardial infarction. Lancet 1968;2:693–700.

9. Research Committee of the Scottish Society ofPhysicians. Ischaemic heart disease: a secondaryprevention trial using clofibrate. Br Med J1971;4:775–84.

10. Carlson LA, Rosenhamer G. Reduction of mortal-ity in the Stockholm ischaemic heart disease sec-ondary prevention study by combined treatmentwith clofibrate and nicotinic acid. Acta Med Scand1988;223:405–18.

11. Coronary Drug Project Research Group.Clofibrate and niacin in coronary heart disease.JAMA 1975;231:360–81.

12. Canner PL, Berge KG, Wenger NK, et al., forthe Coronary Drug Project Research Group.Fifteen year mortality in coronary drug projectpatients: long-term benefit with niacin. J AmColl Cardiol 1986;8:1245–55.

13. Buchwald H, Varco RL, Matts JP, et al. Effect ofpartial ileal bypass surgery on mortality and mor-bidity from coronary heart disease in patientswith hypercholesterolemia: report of the Programon the Surgical Control of the Hyperlipidemias(POSCH). N Engl J Med 1990;323:946–55.

14. Brown BG, Zhao X, Sacco DE, Albers JJ.Atherosclerosis regression, plaque disruption, andcardiovascular events: a rationale for lipid lower-ing in coronary artery disease. Annu Rev Med1993;44:365–76.

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ADDITIONAL MATERIALS

The NHLBI Information Center is a service ofthe National Heart, Lung, and Blood Institute(NHLBI) of the National Institutes of Health.The Information Center provides information tohealth professionals, patients, and the publicabout the treatment, diagnosis, and prevention ofheart, lung, and blood diseases.

NHLBI Information CenterP.O. Box 30105Bethesda, MD 20824-0105Telephone: (301) 251-1222Fax: (301) 251-1223

In addition, the National Heart, Lung, and BloodInstitute maintains a World Wide Web (WWW)site at:

http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm

Below is a list of additional materials obtainablefrom the NHLBI Information Center. Please usethe order form that follows.

Professional Publications

❏ Second Report of the Expert Panel on Detection,Evaluation, and Treatment of High BloodCholesterol in Adults (Adult Treatment Panel II)(NIH Publication No. 93-3095, $5.00 each;package of 25, $106.25; package of 100,$400.00)

Clinical practice guidelines for detecting, eval-uating, and treating high blood cholesterol inadult patients. Full report with references.

Patient and Public Materials

❏ Live Healthier, Live Longer: Lowering Cholesterolfor the Person With Heart Disease (NIHPublication No. 96-3805, $3.00 each; packageof 25, $37.50; package of 100, $120.00)

An essential handbook for CHD patientsdesigned to help lower blood cholesterol levelsto reduce the risk of a future heart attack andprolong life.

❏ Step by Step: Eating To Lower Your High BloodCholesterol (NIH Publication No. 94-2920,$3.50 each; package of 25, $60.00; packageof 100, $225.00)

An information-packed booklet giving down-to-earth advice on how to make diet andlifestyle changes to lower high blood choles-terol.

❏ So You Have High Blood Cholesterol (NIHPublication No. 93-2922, $3.00 each; pack-age of 25, $37.50; package of 100, $120.00)

A booklet explaining what patients need toknow about cholesterol, including how tolower it and where to go for help. Intendedprimarily for patients without CHD, butincludes some information for CHD patientsas well.

❏ Facts About Blood Cholesterol (NIH PublicationNo. 96-2696, single copy, free; each addition-al copy, $1.00; package of 25, $12.50; pack-age of 100, $40.00)

A fact sheet for the public providing basicinformation on cholesterol, how it’s tested,and what can be done to control it.

❏ Eat Right To Lower Your High Blood Cholesterol(NIH Publication No. 92-2972, $1.50 each;package of 25, $18.75; package of 100,$60.00)

An easy-to-read pamphlet providing basicinformation about how simple dietary changescan lower blood cholesterol. Geared to Step Idiet for primary prevention, not Step II forCHD patients.

❏ Check Your Cholesterol and Heart Disease I.Q.(NIH Publication No. 95-3794, single copy,free; each additional copy, $.50; package of25, $6.25; package of 100, $20.00)

A 12-question true-false quiz testing the read-er’s general information on how cholesterolaffects the heart.

29

❏ Check Your Physical Activity and Heart DiseaseI.Q. (NIH Publication No. 96-3795, singlecopy, free; each additional copy, $.50; packageof 25, $6.25; package of 100, $20.00)

A 12-question true-false quiz addressing physi-cal activity and heart health.

❏ Facts About Heart Disease and Women: Self-HelpStrategies for a Healthy Heart—Reducing HighBlood Cholesterol (NIH Publication No. 96-3658, single copy, free; each additional copy,$1.00; package of 25, $12.50; package of 100,$40.00)

A fact sheet of self-help information to helpwomen lower blood cholesterol levels.

❏ Exercise and Your Heart: A Guide to PhysicalActivity (NIH Publication No. 93-1677,$3.00 each; package of 25, $37.50; packageof 100, $120.00)

A booklet providing practical informationand guidelines on physical activity and theheart.

31

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P u b l i c H e a l t h S e r v i c eN a t i o n a l I n s t i t u t e s o f H e a l t hN a t i o n a l H e a r t , L u n g , a n d B l o o d I n s t i t u t e

N I H P u b l i c a t i o n N o . 9 7 - 3 7 9 4S e p t e m b e r 1 9 9 7