Clinical Pharmacy Services for the Hypercholesterolemic Patient

Clinical Pharmacy Services for the Hypercholesterolemic Patient By James M. McKenney

Objectives 1. 2. 3. 4. 5.

Upon successful completion of this module, pharmacists will be able to Define the information the general public should have about high blood cholesterol; Describe the key steps in planning a cholesterol screening program; Describe drug interactions with lipid-lowering agents; Describe drug-induced lipoprotein changes; Describe the individualized approach to enhancing compliance with lipid-lowering drug therapy.

hat clinical services could practicing pharmacists provide to patients with high blood cholesterol? The quick answer would be none. Once the physician has prescribed the treatment and the office nurse has instructed the patient on nutrition, what is the pharmacist to do but dispense the medication? My answer is plenty! I t is not only a good idea for pharmacists to contribute to the care of the hypercholesterolemic patient, it is essential if we are to succeed in controlling high blood cholesterol in this country. Studies have shown that when the pharmacist spends 1 or 2 minutes with the patient each time he renews a prescription , of a maintenance medication, patients are more likely to comply with treatment and achieve good therapeutic outcome. When the pharmacist dispenses these prescriptions without interacting with the patient, even if physicians and office nurses continue to do their job, treatment results are inferior. Pharmacist interaction with the hypercholesterolemic pa-

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tient could translate into better compliance with lipid-lowering therapy, more effective lowering of high blood cholesterol, and less coronary heart disease mortality and morbidity. Pharmacists can contribute to the effort to identify and care for the hypercholesterolemic patient by providing health information to the public, screening the public for high cholesterol, monitoring drug therapy of patients, and promoting compliance.

Providing Health Information Pharmacists have long been a major source of health information for the general public. There is no more fundamentally important service to the public than to disseminate reliable and accurate information. For accurate cholesterol information, the need is great. Currently the public has little information about cholesterol, and that which it has is often inaccurate. Information about fish oils, "cholesterol free" food labeling, and claims from the latest diet book are but a few common examples of mi~information.

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The first step in providing health information is to decide what general information the public needs to know if individuals are to' make informed decisions about their health. This key informatiO'n about cholesterol, summarized in Table 1, includes the following: Coronary heart disease is the leading cause of death and disability in the United States. Thisis an obvious but important initial fact that relates to the cholesterol problem. The United States' number one health problem is heart disease. This is not just a cold health statistic. Coronary heart disease not only affects others, but it can alsO' affect each of us, and odds are it will" unless we do something about it.

1•

High cholesterol levels in the body cause atherosclerosis (arteries become hardened and narrow).

2.

Atherosclerosis leads to coronary heart • disease (eg, heart attacks, coronary artery.disease requiring bypass surgery, .and angina).

3

Statements 2 and 3 link cholesterol and coronary heart disease. Understanding this link is the key to encO'uraging the public to "dO' something abO'ut" their cholesterol. These statements are alsO' intended to help the· public deal with the terminology of the field. The lay terms-heart attack, bypass surgery , and angina-are purposely used. This nO't only makes the information more understandable, it helps personalize it. All O'f us know someone, usually a close relative, whO' has ,had these health problems. This personalization of the message readies the individual fO'r taking action. The higher the cholesterol level in the bpdy, the greater the chance of coronary heart disease. Once the·public understands the link between cholesterO'I and coronary heart disease, the first questiO'n is, "What is high?" It is best to avoid answering the question with a number. TO' identify levels above 240 mg/dl as high, fO'r example, implies that levels below this are normal and carry no risk~ which is nO't the ,case. The best answer is the statement above. The relationship between cholesterO'I and cO'rO'nary heart disease is a continuum. The higher, the worse; the .lower, the better.

4.

Excess cholesterol most often results eating too much of the wrong foods. The public will 'naturally inquire about the cause of high cholesterol levels. The answer is, it is self-inflicted. A few patients have

5• from

Table 1. Cholesterol Information for the General Public • Coronary heart disease is,the leading cause of death' and disability in the 'United States. • . High chole-sterQllevels ,in the body,cause arteries to become hardened ·and narrow. • Hardened and narrow ,arteries (atherosclerosis) leadto ,coronary heart disease (eg, myocardial infarction, angina). • The higher' the .body's cholesterol level, the greater the chance .of coronary heart disease. • An ' excess ·'supply of cholesterol most often comes from eattng to.Q muoh of the ,wrong foods. • Ac.ceptable ,diets and medications that effectively lower cholesterol levels are now available. • Lowering .cholesterol slows, and may even reverse, 'the development of coronary heart .disease'. • Know what your cholesterol level is. If it ·is too high, seek appropri.ate treatment.

genetically determined hypercholesterolemia, but most of us simply eat too much of the wrong things. This fundamentally important concept must be understood and accepted before patients are ,likely to accept treatment recommendations. Acceptable diets and medications are available to effectively lower cholesterol levels. High bloO'd chO'lesterollevels are not indicative of a disease without known treatment. Our treatment.is effective and acceptable. Lowering cholesterol slows and may even reverse the development of coronary heart disease. How far we can go with claims of treatment will probably change with time and further research. -R ight now the above statement seems acceptable. Perhaps one day we can claim regressiO'n O'f disease or cure. The above statement is the,punch line to the cholesterol story. This is ·the reward available to those who act on this information. Furthermore, the -reward is · directly linked to' a visual marker, IO'wering the blood cholesterol level.

6.

7.

Know your cholesterol level and whether it needs treatment. . This is the simple message of the National Cholesterol Education Program of the N ational Heart, Lung, and Blood Institute (NHLBI). A gO'od understanding .of the first seven statements requires action. Individuals should be encouraged to define their level of risk 'and determine whether further action is warranted.

8•

These statements should be the basis for an effective public information prO'gram. They may be incorporated in radiO' messages, flyers put in prescription bags, or signs in the

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Table 2. Sources for Low Cost Consumer Handouts on Cholesterol

The American , He~rt4 Association Diet, " '

pharmacy, or they may be given as verbal advice to those who ask or will listen. These statements are also the starting point of consultation with patients receiving therapy, although more detailed information will be needed in these cases. Public education material is now available from a variety of sources (see Table 2) to enhance this effort.

Cholesterol Screening Since the Coronary' Primary Prevention Trial has shown that lowering blood cholesterol reduces mortality, 1,2 the public 528

health agenda has included first informing the public of these findings and their ramifications and then identifying which individuals need to monitor cholesterol levels. ' Unfortunately, hypercholesterolemia rarely produces symptoms until it results in what is often a catastrophic and debilitating coronary event. If the patient survives this event, treatment is rarely able to restore the patient's original state of health. Thus using symptoms to identify patients needing treatment is not wise. The greatest benefit from ' treatment will

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accrue if individuals with high blood cholesterol are detected and treated early in their life, before complications develop. Thus, population screening similar to the high blood pressure screening effort is needed. The recent availability of portable equipment capable of providing an accurate measure of cholesterol from a capillary sample is making such an effort a possibility, especially for pharmacists. A'dvantages of Cholesterol Screening by Pharmacists

Conducting public cholesterol screening in the community pharmacy has several important advantages. Because of the geographic distribution of pharmad;s in most communities and their accessibility, cholesterol screening in .pharmacies would be available to a wide sector of the population. Furthermore, and of equal importance, the pharmacists in these pharmacies offer a professional underpinning that enhances the screening effort. Pharmacists can answer technical questions, teach patients about the importance of cholesterol, and help individuals with high readings make physician appointments. The pharmacist stands to gain substantially from the screening effort. With all the public interest in cholesterol, the pharmacist's association with screening would be a very visible activity that would undoubtedly enhance his image as a concerned and proactive public servant. In addition, cholesterol screening would substantially increase traffic flow in the pharmacy. The same resources used in screening could also be used in monitoring treated patients and thus enhance the pharmacist's ability to contribute to long-term cholesterol control. Pitfalls in Cholesterol Screening

Planning is the key to a successful cholesterol screening program. Without it, problems are bound to occur. Two problems in particular deserve special recognition and comment. A problem encountered in early cholesterol screening efforts also occurred during blood pressure screening efforts: half the screened patients found to have a high reading and referred for medical evaluation never saw a physician, thus defeating the purpose of the program. This problem needs to be considered and a plan developed to deal with it before the first cholesterol level is determined. Certainly one plan would be to identify physicians willing to see these patients and to assist patients in making appointments with a physician of choice. Of course, effective patient education when making this

referral is also a must. . A second problem encountered in early screening programs is that not all physicians agreed that the cholesterol level of the referred patient should be treated. Numerous reports have been received of patients, found to have very high cholesterol levels during screening that were subsequently confirmed in the physician's office, who were nevertheless told that they did not need care. This is a problem of physician education, requiring that current information on cholesterol treatment filter down to and be accepted by all physicians. One way of enhancing this process is for the pharmacist to include local physicians in planning the screening procedure and establishing the methods for deciding which patients should be referred ' for medical evaluation. P1anning

As indicated above, planning is the key to a successful cholesterol screening program. This step of course needs to occur before the screening program begins. Some key items must be considered when planning a screening program (see Table 3). Record Keeping. Conducting a cholesterol screening program without keeping records is not advisable. At the very least, a log of the patient's name, date of the screening, and cholesterol results should be maintained in case the patient or the patient's physician asks for these results. This may be easily incorporated into the patient's medication record in the pharmacy computer. Information needed by the pharmacist to follow up a patient referred for treatment from the screening includes the address and/or phone number and the physician to whom the referral was made. In addition, pharmacists who are consulting with a physician about a referred patient's results may want to know the conditions of the test (eg, time of day, fasting or nonfasting) and any treatment the patient may currently be following (eg, fish oils, fad diet). Information needed by the pharmacist who wishes to tailor an education program to the patient would include (in addition to the above) information on the current medication regimen, history of prev.ious cholesterol results and treatment, personal and family cardiac history, and presence of other risk factors. What should be obvious is that the information recorded during the screening program is in large measure determined by the services to be subsequently rendered. Whatever the information requirement, the system for obtaining and recording it needs

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Table 3. Planning Considerations for Cholesterol Screening Record keeping Target population Screening equipment Time/space/resource needs Publicity Referral criteria Referral procedures Educational messages Fo"ow-up system

Table 4. Portable Cholesterol Screening Equipment Device

Manufacturer

Reflotron Boehringer Mannheim Diagnostics Ektachem DT60 Eastman Kodak Company Analyzer Vision Abbott Laboratories, Diagnostic Division Seralyzer Ames Division, Miles Laboratories

Telephone 800-852-8766 800-445-6325 (Ext. 492) 800-323-9100 800-348-8100

to be in place before the screening and should efficiently capture needed information. Perhaps the best way to accomplish this is to incorporate the information into the records currently maintained on patients or families in the pharmacy. Screening Equipment. The availability of portable, reasonably accurate, and easy-touse equipment for cholesterol assay has made mass cholesterol screening possible. The number of companies manufacturing these devices continues to grow; some of the more well-recognized devices are identified in Table 4. The. two devices that have received the most attention in regard to early cholesterol screening efforts are the Reflotron (Boehringer Mannheim Diagnostics) and the Ektachem (Eastman Kodak Company). To use the Reflotron, a capillary (fingerprick) sample is placed on a reagent strip and inserted into the machine in a carefully timed procedure (similar to the blood glucose monitors). Results are displayed on a digital board. The Ektachem is similar, differing in that it requires an additional centrifugation step and provides a hard-copy printout of results. Both devices cost several thousands of dollars. Thus distribution of the products is primarily to pharmacists, physicians, and other health groups conducting cholesterol screening programs. Undoubtedly refine-

ments will make these devices more affordable to the general public for self-monitoring. The issue of accuracy and reproducibility of cholesterol results is important but not as critical during screening as it is when making a diagnosis and determining whether treatment will be initiated. Cholesterol levels naturally vary in the same individual from day to day. There is also some variance in the cholesterol results between laboratory determinations and those recorded with a portable device. I t is best to use the screening program to identify individuals who have high cholesterol levels and to confirm these results with repeated measurements (at least two) in the physician's office under standard conditions (eg, testing in the morning after a 12-hour fast.) that are then sent to a laboratory following Centers for Disease Control standard procedures. Physical Requirements of the Screening Site. Screening in a community pharmacy requires an area that can handle a large patient. flow. (Given the experience to date, anyone conducting cholesterol screening should be prepared for a large tllrnout.) If space is limited, some method that win restrict the number of patients screened at {)ne time should be established. Space is also needed to counsel patients found to have high readings. It is not sufficient to hand patients a booklet and send them on their way. This will most assuredly result in poor patient compliance. The pharmacist or some other health professional should provide at least a brief consultation, explaining the results and the reasons for treatment. Handouts could serve to reinforce the verbal consultation. This procedure has been effective in achieving good follow-up compliance by referred patients. Pe.r sonnel Requirements. Personnel requirements for a cholesterol screening program will depend on the nature of the effort. A massive, shopping-center-based, one-day screening with wide community advertising would require many more helpers than would a small, continuous screening service with minimal advertising in a community pharmacy. The latter could conceivably be accomplished by the pharmacist and the pharmacy clerk. The personnel needed would depend not only on the size of the effort but the steps to be performed. At a minimum someone will need to greet the patient and obtain initial information. Someone will have to obtain the sample and operate the screening equipment. And someone will have to consult with the patients who are found to have a high reading l and are referred to a physician. It is con-

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ceivable that the same individual can be trained to perform each of these tasks. I t is also obvious that the more professionals with ' special skills who are used (pharmacists, nurses, dietitians), the better the screening effort. Liability Waiver. Anyone conducting a cholesterol screening program should have patients sign a liability waiver prior to participating. In spite of the very low risk of the procedure and the public service nature of the screening, problems can occur. An example of such a waiver is included in Figure 1. Referral Criteria. According to the National Cholesterol Education Program, cholesterol levels above 240 mg/dl are considered high, levels between 200 mg/dl and 240 mg/dl are borderline high, and levels less than 200 mg/dl are desirable. A cholesterol screening program should do no less than refer all patients with high levels. Patients with levels between 200 mg/dl and 240 mg/dl may be invited back to the pharmacy or referred to a physician to have a repeat measurement. Those patients whose cholesterol is still within the borderline range should be advised to follow a low-fat diet and to have a repeat cholesterol measurement. Selecting the cholesterol level prompting referral to a physician should be done with caution. If all patients with cholesterol levels above 200 mg/dl are referred to a physician, nearly one-haIf the adult population would be referred. Our health system could not withstand this onslaught. However, patients with borderline high levels are at increased risk and should not be ignored. To repeat. measurements of these patients' cholesterol levels and refer all who have levels above 240 mg/dl is perhaps the best plan. Final decisions on referral criteria would best be developed in cooperation with community physicians. Referral Procedure. The simplest referral procedure would be to tell patients with a high cholesterol reading to see their physician. Unfortunately, this is also the least effective method; a large number of patients will never see their physician, raising doubts about the usefulness of the.screening effort. One reason patients fail to go to a physician is that they do not have one or cannot find one. An advantage of having pharmacists involved in the screening effort is their knowledge of which local physicians may be willing to accept patient referrals for cholesterol management. A list of these physicians should be developed and given to patients. If the patient agrees, assistance may be provided in obtaining an appointment with the physician.

Regardless of the procedure followed in obtaining a physician referral, a timely evaluation is crucial. Studies have clearly shown that the sooner the physician's evaluation is scheduled after the screening, the more likely the patient will keep the referral appointment and comply with treatment recommendations. Patient Education. The majority of screened patients will need only the general public information in Table 1. Referred patients will need additional information. They need to understand that their cholesterol level is the total amount of several fractions and that these fractions may be associated with a lower risk of coronary heart disease (ie, high density lipoprotein [HDL] cholesterol- "good cholesterol', or with a higher risk of coronary heart disease (low density lipoprotein [LDL] cholesterol- ''bad cholesterol"). Once they understand this concept, they are more likely to see their physician to have a lipoprotein profile done. Follow-up. A screening program without follow-up is like the stock market without the Dow Jones Average. There will be no overall measure of success. Follow-up tells whether referred patients kept their physician appointments and-where the program may be improved. Follow-up may be accomplished by sending a postcard to the physician for information regarding the patient's compliance with the referral, calling the physician's office, or calling the patient. A second, even more important reason for a follow-up procedure is to identify patients who did not comply with the referral and to encourage them to do so.

I hereby release from any and all liability arising from or in any way connected with blood drawing for my blood cholesterol measurement or from the data derived. I understand that: 1. The data derived from this test are to be considered preliminary only and do not constitute a diagnosis of hypercholesterolemia. 2. With my permission, screening sponsors may elect to send the results of this test to a physician of my choice if my results suggest that I may be at increased risk for heart disease according to the National Institutes of Health guidelines. 3. The responsibility for initiating a follow-up examination to confirm high blood cholesterol and obtain advice and treatment is mine and not that of my physiCian or the organizations associated with this screening. Signature _ _ _ _ _ _ _ _ _ _ _ Date _ _ _ _ __

Figure 1. Sample Cholesterol Screening Consent and Release Statement

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Table 5. Drug Interactions with Anion Exchange Resins Drugs Warfarin Digitoxin Digoxin ' Thyroid Thiazides Hydrocortisone Naproxen Tolbutamide Penicillin Cloxacillin Cephalexln Vitamin A Folic Acid Vitamin 8 12 Nicotinic Acicft WiF

Monitoring Drug Therapy Pharmacists playa key role in monitoring drug therapy because of side effects that often limit compliance and potential interactions with other drugs. .J Drug Interactions with Resins

Cholestyramine and cholestipol .are both anion exchange resins. Both are unaffected by digestive enzymes, remain unchanged in the gastrointestinal tract, and are not absorbed. Both agents bind bile acids during en terohepatic circulation. Unfortunately, these resins can bind drugs in the gastrointestinal tract, prevent their full absorption, and diminish their therapeutic effect. As illustrated in Figure 2, binding can occur in the stomach when the resin and a drug are given together. The binding can also occur in the lower gastrointestinal tract when drugs or active metabolites in enterohepatic circulation come into contact with the resin. The dnig products in Table 5 reportedly interact with the anion exchange resins in man. The most important of these may be warfarin and digoxin, because of a potentially serious adverse outcome. The combined administration of a resin with Vtrarfarin results in an increased elimination rate. In one study, the half-life decreased 35 % and the total clearance increased 45 %. This resulted in a clinically significant reduction in prothrombin activity of about 250/0. The interaction with digitalis glycosides is similar. Coadministration with a resin reduces the bi'o availability of digoxin by about 30%. 'Since digitoxin undergoes greater enterohepatic circulation, bioavailability is 532

reduced to a greater extent. No studies are available to describe how this interaction may alter therapeutic effects. Because the mechanism of these interactions is thought to be reduced absorption of the drug from the stomach and increased clearance via enterohepatic circulation, administering separate doses of the resin and drug should help minimize the interaction. Studies have confirmed that this reduces interference with the drug's absorption from the stomach but will probably have little effect on binding lower in the gastrointestinal tract. Administering digoxin 8 hours before administering cholestyramine results in a very small reduction in bioavailability, whereas concurrent administration of the drugs produces the greatest change. Management of this interaction depends on the patient's illness and need for treatment. It would be best to avoid concurrent administration of warfarin and digitalis glycosides with a resin if possible. If the two interacting drugs must be given to the patient, their administration times should be spaced as far apart as possible. For example, the resin may be administered twice daily in the early morning and at bedtime (or once daily at bedtime) and the interacting drug administered once daily at mid-day. When two potentially interacting drugs ' are administered together, the therapeutic effect (eg, the prothrombin time with warfarin, heart rate and patient symptoms with digitalis glycosides) should be closely . monitored. Drug Interactions with Clofibrate

In contrast to the resins, drug interactions with clofibrate result in enhanced pharmacologic effect of interacting drugs (Table 6). Interaction with clofibrate is thought to occur in two ways. Clofibrate is highly bound to plasma proteins, including albumin. Thus it competes for these binding sites with other highly bound drugs. Drugs such as warfarin and sulfonylureas, which are bound 'greater than 950/0 to plasma proteins, appear to 'be affected in this manner. Clofibrate also appears to alter the receptor site of some drugs so that the therapeutic effect is enhanced. In many cases, this may be the primary mechanism underlying the interaction. Available evidence suggests that clofibrate enhances warfarin's effect on the synthesis of vitamin K-dependent clotting factors, thus producing an exaggerated hypoprothrombinemic effect. Displacement from protein binding sites may also be involved. The same dual mechanisms can be operating with sulfonylureas. In addition to displacing sulfonylureas from plasma protein

American Pharmacy, Vol. NS27, No. 11, November 1987,8~2

binding sites, clofibrate can decrease the resistance of insulin receptors and thus enhance the hypoglycemic effect of the drug. Studies have shown that clofibrate can significantly lower blood glucose levels and improve tolerance in insulin-dependent diabetics. Regardless of the mechanism, the interactions involving clofibrate, especially those with warfarin and sulfonylureas, are clinically important and should be carefully monitored. The combination of interacting drugs should be avoided if possible. If the drugs must be given together, a stable dose of clofibrate should be established before the interacting drug is initiated, and then titration of the dose with careful monitoring is recommended. With warfarin, weekly prothrombin times should be determined to guide these dose titrations. For sulfonylureas, home glucose monitoring or office laboratory evaluations should be completed periodically during the dose titration phase.

Table, 6. Drug Interactions with Clofibrate Drugs ,

J['

Warfarin Sulfonylureas Insulin ' Furosemide

Mechanism

'

prote, in diSP . lacement Receptor sIte alteration

.

J

Action [MOnitor for enhanced response (esp. as start and stop therapy)

Table 7. Diuretic-Induced Changes in Cholesterol 0/0 Ghangewith Treatment

Diuretic

1-12 Months

Thiazide; Loop 'KSparing Indapamide

1 to 13% ' 5 to 7% --8 to 2% "+ - 'S to S%

, 12 + Months

o to 50/0 0%

-1 to 0 0/0 0%

Diuretic-Induced Hypercholesterolemia

Monitoring hypercholesterolemic patients should also seek to uncover drug-induced problems. Recently, clinicians have been concerned about the possibility that thiazide diuretics increase coronary heart disease deaths because of drug-induced hypercholesterolemia. The Multiple Risk Factor Intervention Trial (MRFIT) evaluated the impact of treating three risk factors-high blood pressure, smoking, and cholesterol-in a large patient population in a well-controlled multicenter study. 3 The results showed that aggressively treating patients with a diastolic blood pressure above 100 mm Hg predictably resulted in a reduction in mortality compared with a less aggressively treated group. However, patients with diastolic blood pressure between 90 mm Hg and 94 mm Hg, who received aggressive treatment, had a higher death rate than those receiving less aggressive treatment. The reason for this has never been absolutely identified, but it has been widely speculated that the antihypertensive treatment, especially the thiazide diuretics, may have contributed to this outcome either by causing hypokalemia or hypercholesterolemia. Whether thiazide diuretics actually caused the increased deaths may never be known, but speculation that they did helped highlight a potentially significant problem with these agents. Unfortunately, the problem may have been overstated. Thiazides do cause an elevation in total cholesterol and LDL cholesterol of about 80/0 and 12%, respectively (Table 7). These changes are seen with all agents in this class

including chlorthalidone. They appear to occur with all doses used clinically, doses from as low as 12.5 mg daily to 100 mg daily of hydrochlorothiazide. However, these increases are apparently short-lived. The 8% to 120/0 increases occur initially but after a year or more of treatment, the increases are minimal, in the 2% to 30/0 range. If the 8% to 12% increases persisted, thiazide-induced hypercholesterolemia would be a clinically important problem. However, if the longterm change is but 20/0 to 30/0, thiazideinduced lipid changes are not a maj or problem. Rather than concluding that thiazideinduced hypercholesterolemia is of no importance, a conclusion supported by average data,it may be best to closely monitor the individual patient for cholesterol-level changes. If thiazides induce clinically significant hypercholesterolemia in an otherwise healthy patient, or if they worsen an already significantly elevated cholesterol level in a patient, the effect is important and warrants attention. In these cases, ~ low-fat diet may easily correct the problem. Alternatively, if the change persists, the thiazide diuretic may be discontinued and replaced with a loop diuretic, indapamide, or potassium-sparing diuretic, each of which has little or no effect on cholesterol levels (Table 7). Beta-I;Ilocker-lnduced Hypercholesterolemia

Beta-blockers produce two principal adverse effects on serum lipids, an increase

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Table 8. Beta Blocker-Induced Changes in Lipids Changes in Lipids Type of Action ', Nonselective Selective ISA a & {3 Blocker

TC (0/0)

TRIG (0/0)

HDI:- (0/0)

....;5 to 9 '

9to 51 36 -12 to 2 -12 to 2

-20 to -13 to -2.to -21 to

-7 to 5 -2 to 2 -14 to 0

6 to

-4 - 2" 20 23

TC = total cholesterol; TRIG = triglycerides; HDL =high-density lipoproteins.

in triglycerides and a decrease in HD L cholesterol (Table 8). The increase in triglycerides may be substantial, 20% or more, but since triglycerides are poorly correlated with coronary heart disease deaths, this change may not be very important. The exceptions to this ' would be patients who develop levels substantially higher than 250 mg/dl and patients with underlying triglyceridemia. Whenever levels exceed 250 mg/dl, action should be taken, probably dietary modification. If levels exceed 500 mg/dl or if patients develop symptoms of pancreatitis, the beta-blocker should be stopped. Changes in HDL cholesterol are more clinically important. HDL is independently and inversely related to the incidence of coronary heart disease. The lower the level, the higher the risk of problems. Thus, drug-induced reductions in HDL ' are potentially serious. HDL reductions with beta-blockers are neither dose nor duration related, nor are they seen uniquely in certain segments of the population. However, they do appear to be more pronounced with nonselective than selective beta-blockers (Table 8). Betablockers that have either an intrinsic sympathomimetic effect (ISA) or alpha blocking effect (such as labetolol) appear to have the least adverse effect on HDL. When monitoring an individual patient, significant reductions in HDL (greater than 10%) should be cause for action. The patient 'snonselective agent can be replaced with a selective agent or one that has other features. If these agents also cause significant changes, 'beta-blocker therapy should be replaced with other suitable drugs. Oral-Contraceptive-Induced Hypercholesterolemia All oral contraceptives cause at least a modest increase in LDL cholesterol, regardless of their exact combination of estrogen and progestogen. It is apparent that those oral contraceptives with the lowest estrogen potency and the highest progestogen potency 534

(eg, Ovral and N orlestrin) cause the greatest increases in LD L cholesterol and the greatest decreases in HDL cholesterol. Oral contraceptives with a more balanced formulation between estrogen and progestogen (eg, Ortho-Novum and Enovid) cause only a modest rise in LD L cholesterol and may even cause an increase in HDL ,cholesterol. Estrogen replacement therapy in postmenopausal women causes a 10% decrease in total cholesterol, a 30% decrease in LDL cholesterol, 'and a 30% increase in HDL cholesterol. Therapy with equine estrogen in premenopausal women produces a 15% increase in LDL cholesterol and a 10% increase in HDL cholesterol.

Encouraging Compliance Compliance with chronic drug therapy is typically abysmal. There is no reason to believe that compliance will be any better with lipid-lowering therapy'- Fortunately, I believe this problem can be solved, and the pharmacist is the one to do it. The Coronary Primary Prevention Trial results indicate that compliance with longterm resin therapy , for some patients is poor.1· 2 More than half of all patients were noncompliant with their cholestyramine medication regimen. Patients consumed about 600/0 of prescribed doses. Results clearly indicate that patients who took the majority of their doses lowered their blood cholesterol level most significantly and had the lowest death rate. Patients who were poorly compliant or fully noncompliant had little change in their cholesterol level and experienced the highest death rate among treated subjects. These results help underline the importance of compliance, not only to decrease cholesterol levels but also to save lives. Assumptions Before developing a compliance service, pharmacists must understand several assumptions that represent pitfalls to effective compliance interventions:

• There is no demographic profile of the noncompliant patient. Anyone, regardless of ethnic origin, sex, education, social status, or affluence, can be noncompliant with therapy. • There is no one cause of noncompliance. There are, rather, dozens of causes of noncompliance, including cost of therapy, medication side effects, forgetfulness, and denial of the need for therapy. • No single approach resolves noncompliance because so many causes operate in a given patient population. Even the most effective patient education program cannot

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be expected to assure compliance in all patients . • No intervention has a lasting effect. Even highly successful efforts to improve compliance will become less effective with time, and new intervention techniques will be required. ' • Compliance is a behavior. Thus an effective compliance-improving protocol would include a behavioral perspective~ Approach

Noncompliance can be resolved. Although many have tried and failed, there is an effective solution to this problem, the ingredients of which are the pharmacist and the approach. The pharmacist (or any health professional) must be willing to provide personalized services to patients. Handing out patient education materials will fail. The only way to improve patient compliance is through caring, informed professionals who are willing to devote the time and energy to personalized services. The second ingredient of a successful compliance program is the approach. The hallmark is specific services tailored to specific causes of noncompliance in individual patients-in other words, individualized care. Too often in the past, investigators have sought to resolve noncompliance with a general approach, one given to all patients. For example, teaching all patients to measure their blood pressure at home and thus making them able to monitor their treatment results makes sense and has clearly been successful in prompting compliance in some patients. However, self-monitoring is not effective in resolving all patient noncompliance because such an approach fails to meet the needs and causes of noncompliance in all patients. Some patients are noncompliant because they cannot read the prescription label, understand the prescribed dosing regimen, or afford to purchase the drug each month. For these patients, self-monitoring of blood pressure or cholesterol levels will make little difference in their ability or interest in complying. A more successful approach recognizes that each patient's reason for noncompliance is unique. The key to unlocking the problem and promoting compliance is to resolve or at least address the cause of noncompliance in the individual patient. Tailoring services to these causes should remove barriers to full compliance. The most effective compliance program will use three services to address individual causes of noncompliance: information services (eg, teaching patients about their illness and therapy), social services (eg, encouraging

family support), and behavioral services (eg, reminder systems, rewards). Information Services. In developing information services in a compliance program, certain general principles should be kept in mind: • Knowing doesn't mean doing. Knowledge alone may not prompt compliance. • Knowledge is indispensable. The patient cannot comply if he does not know what is expected. • Turning knowledge into beliefs is key. The patient must accept the information for it to be meaningful. • Personalizing instruction is most effective. Telling patients what they want and need to know and answering their questions is the key to a successful education program.

Figure 2. Mechanisms of Resin-Drug Interactions

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shO'uld be taken within one-half hour of each meal to enhance its effects. Patients need to be encouraged to experiment with the liquid they like best for mixing with their resin. To cut down on the time to prepare doses and to enhance the mixing of the drink with the resin, patients should be advised to mix their daily dose in a blender each day. They should also be advised to drink their dose slowly to prevent belching. The pharmacist should p~rsonally provide this information along wIth handout materials to reinforce-the instructions at home. (Examples of available patient education materials are listed in Table 2.) When the patient returns to the pharmacy for refills, the pharmacist should inquire about successes -and problems and / use this information to personalize further instructions.

• Reinforced information is best. Repeating instructions and using printed materials with verbal consultation improve retention. • The best information is usable. Instructions must be practical to be meaningful. • How we say what we say is important. Good communication techniques enhance patient education. Applying these principles in developing information services about lipid-lowering drugs will help enhance the success of th~ compliance program. Information needed by the general public is outlined in Table 1. The patient with hypercholesterolemia who is prescribed drug treatment needs-this same information. In addition, patients receiving drug therapy for the first time need to ' understand the goals of therapy. The more specifically the goal is s~ated, the better. For example, most patIents should be encouraged to attain the lowest possible total cholesterol or less than 200. mg/dl if possible. Patients receiving initial drug therapy should also be taught that the effect of treatment is proportional to the dose consumed; the closer to full compliance, the greater the . reduction in plasma cholesterol. Patients should also understand that drug therapy is intended to be chronic. Drugs control but dO' not cure high blood cholesterol. Patients should not stop therapy because they fear that the drug product will produce tolerance, cause addiction, cause adverse effects, or any of a thousand other reasons. Patients being started on resin therapy should be given special instructions to help them comply with the treatment. A dose 536

Social Services. The social services of a compliance program may have the greatest and mpst lasting impact. Studies have consistently shown that when a spouse or entire family participates in a caring way with the patient's therapy, success is greater. This may be especially true with hypercholesterolemic patients where diet and drug therapy are both important components of the treatment program. Compliance with diet because the family has adopted it as well may also enhance the effectiveness of drug treatment. , Providing social services means involving a family member or friend in the patient's therapy, preferably with the patient's approval. The family member can be involved only in a general way, offering encourage- ment but not needling. Occasionally, more active involvement is required when the patient is having trouble with compliance and is willing to have a family member help. For example, family members may remind patients when it is · time to take the medication, { prompt the patient to obtain prescription renewals in a timely manner, or help patients manage side effects. If family members or friends are to be included in the patient's care, they should be given proper support and feedback. They too need general and specific instruction on cholesterol and its treatment. Just as important, they need feedback on the patient's progress and changes in therapy. The pharmacist will find the family an important ally in encouraging compliance. Behavioral Services. Behavioral services do not refer to mystical or clandestine maneuvers~ Behavioral services -are simply techniques aimed 'at improving some aspect of the patient's regimen compliance. Methods for encouraging and supporting compliance

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include several behavior modification techniques: Feedback: Tell the patient how he is doing. Do not assume the patient either knows or cares; give the patient information needed to continue the program successfully. A good example of feedback is providing the results of a cholesterol determination. Reward: The patient who is rewarded for good compliance is more likely to comply in the future. Rewards most often are praise and encouragement. Some pharmacists have developed more elaborate approaches to encourage further compliance, such as offering free cholesterol determinations or providing free medication samples. Tailoring: This technique attempts to fit the therapy to the patient's daily routine and hab!ts. Most often it involves developing a dosIng schedule that considers the patient's eating habits. Tailoring may also involve the use of bulk resin at home and packets during work trips or at the office. Cueing: Cueing is a technique for reminding patients of dosing times. Examples include coinciding doses with 'meals and programming watches to signal dosing times. After these reminders have established habitual practice, the patient can often do without them. Self-care: Self-care involves the patient in his treatment program and decision making. It assumes that basic instruction has been given and the patient understands the care and possible outcomes of the program. Examples of self-care are recording doses on a calendar or charting cholesterol results. The ultimate in self-care is home cholesterol measurements and patient-initiated dose titration with periodic consultation over the phone with the physician. Supervision: This technique implies oversight of the patient by a health provider. The health provider asks about compliance and makes it an issue during each visit. He develops an unwritten supervisory position with the patient and works with the patient to maintain compliance. The best example of this is the ,p harmacist who meets with the patient each time he returns for prescription renewals and asks about successes and failures with the therapy. Shaping: This technique is used to introduce complicated regimens slowly and incrementally so that the patient is more likely t? ac~ept them. An example is the upward tItratIon of the dose of a resin. Rather than giving the patient a full dose at first, the dose is increased only when the patient has mastered and accepted the first dose. Hurdling: This technique implies the pa-

tient is taught problem-solving, a vital abilit:y that a!l0ws the patient to deal effectively WIth barrIers to therapy rather than give up. Some of the problems patients may encounter with resins have possible solutions: • Constipation-Recommend diet fiber or laxative therapy. • Bloating-Advise the patient to use antacids. • Belching-Teach the patient to drink the resin mixture slowly. • Expense-Change from packets to bulk powder and to less expensive comparable alternatives. • Bulky Stools-Warn the patient to expect bulky stools and not to be concerned. • Bad Odor-Suggest a change of resin. • Sandy Texture-Suggest a change of resin. • Traveling-Dispense individual packets or give small containers. • Missed Doses- Recommend doubling next doses. Suggest memory aids. The Challenge Under the aegis of the National Cholesterol Education Program (of which APhA is a charter member), a national effort to identify and treat individuals with high blood , cholesterol is clearly gathering momentum. I t will not be long before the cholesterol message will be displayed everywhere. Screening programs will be plentiful. New drug therapies will be available. Patient education materials will be commonplace. Continuing education programs will be frequent. The real question at present for each community pharmacist is, How are you going to be involved? Will you offer cholesterol screening or patient education in your pharmacy? Will you monitor patients for potential drug interactions? Will you seek to improve patients' compliance with lipid-lowering therapy? You do have a maj or role to play. By becoming involved, not only will you contribute to public health and possibly save lives, but you will bring to pharmacy the professional recognition it deserves. ®

References 1. Lipid Research Clinics Program, Journal of the American Medical Association, 251, 351 (1984). 2. Lipid Research Clinics Program, Journal of the American Medical Association, 251, 365 (1984). 3. Multiple Risk Factor Intervention Trial Research Group, Journal of the American Medical Association, 248, 1465 (1982).

James M McKenney, PharmD, is professor, School of Pharmacy, Virginia Commonwealth U,:iversity, Medical College of Virginia, RlChmond.

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