Role of the Pharmacist

Michael Bottorff, Pharm.D., FCCP

The prevalence of cardiovascular risk factors continues to rise, withconsiderable emphasis on the upward trends in obesity and diabetes mellitus,which have increased by 46% and 60%, respectively, in the past 10 years. Thealarming increase in the prevalence of diabetes and obesity has resulted in thedevelopment of new and innovative drug therapies to assist in managingcardiometabolic risk factors. This advent creates many opportunities forpharmacists to evaluate patients’ drug regimens and influence lifestylemodification. Drug therapy management programs allow pharmacists to takeactive roles in assessing drug regimens and to intervene as appropriate. Nomatter what their practice environment, pharmacists have numerousopportunities to recognize and recommend treatment for cardiometabolic riskfactors and to increase patient compliance by educating patients and healthcare practitioners.Key Words: drug management programs, cardiometabolic risk factors,pharmacists, compliance.(Pharmacotherapy 2006;26(12 Pt 2):227S–232S)

The prevalence of the major cardiovascular riskfactors continues to rise. Trends over the past 10years have shown an increase in hypertensionand high cholesterol. However, the most alarmingtrends are in diabetes mellitus and obesity. Theprevalence of diabetes and obesity has increasedby 46% and 60%, respectively, over the past 10years, with the rate of obesity being considerednearly epidemic.1 In statistical terms, peoplewho are obese by the age of 40 years have a 7-year decrease in their overall life expectancy.2 Inaddition, such individuals have a 5-fold increasein the risk of hypertension and more than a 3.5-fold increase in the risk of coronary heart disease.Over 90% of patients with type 2 diabetes have abody mass greater than 23 kg/m2.1 Thesefindings confirm the important role obesity playsin a variety of cardiovascular risk factors.However, the risk associated with obesity is not anew concept. In the 5th century BC, Hippocratesstated, “corpulence is not only a disease itself,but it is the harbinger of others to come.”3

Role of the Pharmacist in ImprovingCardiovascular Disease Risk and PatientOutcomes

The alarming increase in the prevalence ofdiabetes and obesity has resulted in the develop-ment of new and innovative drug therapies to aidin managing cardiometabolic risk factors. Thisadvent of new therapies provides pharmacistopportunities to evaluate where these treatmentsmight fit in their day-to-day practice in terms ofimproving patient outcomes and determining therole they can play in improving screening forcardiovascular risk factors. Roles of the phar-macist in improving the risk of cardiovasculardisease include communicating the desiredoutcomes and targets with patients to improvetheir therapeutic compliance (i.e., followingdirections for use and taking doses as prescribed)and adherence (i.e., continuing with a drugregimen and not discontinuing it without theapproval of a health care provider), assessinggaps in therapy (e.g., missing drugs, overuse orunderuse of drugs in a regimen), collaboratingwith health care providers, and being activeparticipants in therapeutic decision making toensure that patient therapy is appropriate toachieve the desired outcomes.

From the Department of Clinical Pharmacy, University ofCincinnati, Cincinnati, Ohio.

Address reprint requests to Michael B. Bottorff, Pharm.D.,FCCP, Department of Clinical Pharmacy, University ofCincinnati, 3223 Eden Avenue, Cincinnati, OH 45267.

Supplement to PHARMACOTHERAPY Volume 26, Number 12, 2006

Pharmacist Interventions Can Improve Patients’Adherence to and Persistence with Therapy

Several studies recently demonstrated theundertreatment and mismanagement of patientswith cardiometabolic risk factors. Opportunitiesfor pharmacist intervention can be identified inthe literature. If implemented, they can improveoverall management of risk factors.

Investigators conducted a 1-year assessment todetermine patient adherence to recognizedcardiovascular drug therapies that were known toreduce cardiovascular morbidity and mortality.4

They evaluated 1326 patients who were takingaspirin (95%), b-blockers (86%), angiotensin-converting enzyme inhibitors (65%), and/orstatins (55%). At 1 year, 18% of the patientsdiscontinued aspirin therapy, 22% discontinuedb-blockers, and 28% each discontinuedangiotensin-converting enzyme inhibitors andstatins. Overall, only 54% of patients wereadherent to all of the originally prescribed drugregimens. Nonadherence rates were higher inolder versus younger patients, in women, inpeople who were unmarried, and in those hadrelatively low levels of education. These resultsemphasized the strong need to increaseinteraction with patients and to identify factorsfor improving the assessment of nonadherenceand noncompliance.

In a similar study, researchers identified twotypes of contributors to poor blood pressurecontrol rates in patients with hypertension,namely, patient factors and physician factors.5

Patient factors included obesity, drug costs,complicated drug regimens, adverse effects, andpoor social support. These patient factors createopportunities for pharmacist involvement toimprove patient education and increase overallcompliance. Physician factors were related to alack of awareness of treatment guidelines,overestimation of patient adherence to therapy,and concern for adverse effects. Pharmacistshave an opportunity for intervention byeducating physicians about nationally acceptedguidelines, by working with physicians ontherapeutic follow-up (e.g., by providinginformation about refill rates), and by educatingphysicians about adverse effects and theirimportance in overall patient therapy (e.g., byhelping them determine if the benefits oftreatment outweigh the risk of adverse effects).

Similar patterns were observed in anotherimportant area of risk-reduction management forpatients with cardiometabolic risk without

cardiovascular disease. Using a large prescriptiondatabase, researchers reviewed therapeutic persis-tence rates for statin drugs in 25,733 patients.6

At 6-month follow-up, 30% of patients to whoma statin was prescribed discontinued statintherapy. Discontinuation rates at 1 and 3 yearswere even greater, at 50% and 60%, respectively.Of interest, noncompliance with therapy wasassociated with the consultation of multiplephysicians and several pharmacists. Patientsshould be encouraged to maintain their prescrip-tions at a single pharmacy or pharmacy system.Such containment of prescription dispensingimproves evaluation of adverse-effect profiles,refill rates, and drug interactions. Rates ofpersistence with therapy were notably increasedamong patients who were recently hospitalized orwho had comorbid conditions, such as hyper-tension or diabetes. Potential reasons for enhancedpersistence in this population were frequentvisits to health care providers, improved access toproviders, and additional education about thenature of their disease and the importance ofcontinuing drug therapy.

Pharmacist Interventions Can Improve theAchievement of Target Outcomes in Patientswith Cardiovascular Disease Risk Factors

In the National Cholesterol Education ProgramEvaluation Project Utilizing Novel E-Technology(NEPTUNE) II study, clinicians evaluated 4885high-risk patients by using an electronic surveyto assess the rates at which they achieved goalsfor low-density lipoprotein cholesterol (LDL).7

About 57% of high-risk patients achieved theLDL goal of less than 100 mg/dl. Also of interestwas that only 27% of patients who had hightriglyceride levels in addition to high LDL levelsachieved the combined treatment goal of an LDLlevel of less than 100 mg/dl and a non–high-density lipoprotein treatment goal of 130 mg/dl.Perhaps this high-risk patient population requirescombination therapy, but practitioners are leeryof prescribing combination therapy because ofadverse effects. Once again, here lies an oppor-tunity for the pharmacist to provide educationabout effective and safe drug therapy.

Pharmacists have many opportunities tointervene and improve overall management ofcardiometabolic risk factors, including hyper-tension, dyslipidemia, and diabetes. Pharmacistshave traditionally focused on drug therapy. Withthe increased prevalence of cardiovascular diseaseand cardiometabolic risk factors and with the

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ROLE OF THE PHARMACIST Bottorff

pronounced effectiveness of lifestyle modifi-cation, pharmacists need to emphasize theintimate interaction of these two therapies insuccessfully reducing risks.

Pharmacists’ Influence on LifestyleModification

It has been stated that “with fat, diabetesbegins; from fat, diabetics die.”8 This highlightsthe recognition of the relationship betweencardiometabolic risk factors in diabetes.

Lifestyle modification, specifically dietarychanges and exercise, have recently beenaddressed in the medical literature. It is far tooeasy to say that an issue as complicated as obesitycan be addressed solely with the introduction of adrug. Dietary control and other nondrugmeasures, such as exercise, are importantcontributors to the overall process of managingobesity as a cardiometabolic risk factor.

One study was designed to answer if drugtherapy or lifestyle modification produces thebest results.9 In this trial, 224 obese adults wererandomly assigned to receive sibutramine 15mg/day, intensive counseling about lifestylemodification, sibutramine plus intensivecounseling about lifestyle modification, orsibutramine plus brief counseling about lifestylemodification. All patients were given a diet thatlimited caloric intake to 1200–1500 kcal/day,with exercise. The combination of lifestylemodification and drug therapy substantiallyimproved results. The combined therapy ofintense lifestyle modification and sibutramineresulted in a mean weight loss of 12.1 kgcompared with 5.0 kg in with only sibutramine.Likewise, patients receiving brief counseling

about lifestyle modification in combination withsibutramine lost a mean of 7.5 kg. The bestoutcomes were achieved with combinationtherapy.

Studies have also been conducted to evaluatethe relative benefits of lifestyle modificationversus drug therapy in patients with metabolicsyndrome to prevent type 2 diabetes. One of themost important studies was the DiabetesPrevention Program, which included 3234individuals with an impaired glucose tolerancewho were at high risk for developing diabetes.10

Patients were randomly selected to receiveplacebo, metformin 850 mg/day, or a lifestylemodification program that included monthlymeetings with a case manager, a goal of 150minutes of exercise/week, and a weight-loss goalof 7%. During 2.8 years of follow-up, the intenselifestyle modification group had a 58% reductionin diabetes compared with a 31% reduction in themetformin group. Again, lifestyle modificationwas a key factor in reducing cardiometabolic riskfactors.

Pharmacists’ Role in Lipid Level Management

Lipid management is another important areawhere pharmacists can improve overall treatmentstrategies. The National Cholesterol EducationProgram (NCEP) provided guidelines to categorizepatients into those at moderately high risk, highrisk, or very high risk for cardiovascular events.11

Table 1 provides details about these NCEP goals.Recent clinical trials indicate the need to reach

more aggressive LDL goals than previouslyindicated. Results from these trials are summa-rized in Figure 1.12 Compared with less inten-sive therapy in patients whose LDL levels were

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Table 1. Low-Density Lipoprotein Cholesterol Goals and Recommended Levels for Starting Drug Therapy from theNational Cholesterol Education Program Interim Report11

Recommended Level forLDL Goal Starting Drug Therapy

Risk Description (mg/dl) (mg/dl)a

Moderately high Two or more risk factors; 10-year risk of 10–20% < 130 ≥ 130,b consider if 100–129< 100 optional

High CHD or CHD risk equivalents, 10-year risk > 20% < 100 ≥ 100b

Very high Established CHD plus several major risk factors, < 100 ≥ 100,b consider if <100severe and poorly controlled risk factors, < 70 optionalseveral risk factors for metabolic syndrome,or acute coronary syndromes

LDL = low-density lipoprotein cholesterol; CHD = coronary heart disease; CVD = cardiovascular disease.aWhen LDL-lowering drug therapy is used, the intensity of therapy should be sufficient to achieve a 30–40% reduction in LDL levels.bTherapeutic lifestyle changes should be started when the LDL level is at or above the goal. Any high-risk or moderately high-risk patient whohas lifestyle-related risk factors is a candidate for therapeutic lifestyle changes regardless of LDL level value.

Supplement to PHARMACOTHERAPY Volume 26, Number 12, 2006

approximately 100 mg/dl, patients who achievedLDL goals of approximately 75 mg/dl had anadditional 16% reduction in the risk of coronarydeath or myocardial infarction.12 As a result ofthese trials, the NCEP now recommends patientsat very high risk for cardiovascular events haveLDL goals below 70 mg/dl.

The bottom line is that as LDL loweringbecomes increasingly aggressive, the reduction inthe rate of coronary heart disease events over thenext several years will become progressivelyevident. Minimal management of LDL level is nolonger sufficient. As the optimal goals for LDLbecome increasingly aggressive, the need forcombination therapy rises. The pharmacist canplay an important role in helping patients safelyachieve aggressive LDL goals in the most cost-effective manner.

So, what might the role of the pharmacist be inmanaging lipid levels in patients at high risk forcardiovascular events? Data have shown thatinadequate prescribing or poor patient adherencecan limit the benefits of lipid-lowering therapy.5–7

Pharmacists are in a unique position betweenpatients and physicians to be able to interact withboth to alleviate the challenges that limit thereduction of cardiometabolic risk factors.

The literature provides several examples ofpharmacist-initiated lipid interventions thatincreased achievement of LDL treatment goals byimproving patient compliance and patienteducation in a time-efficient and cost-effectivemanner.13, 14 One group of researchers assessedthe role a pharmacist can play in improvingcompliance in patients who were alreadynonadherent to lipid-lowering therapy.14 Patientsreceived a 30-minute consultation from apharmacist about the importance of lipid levelmanagement and about the role drug therapyplays in improving their cardiovascular risk.During this session, a blood sample was drawn toassess their baseline LDL levels. Follow-up was atelephone call to the patient at 2 and 4 monthsafter the initial visit. Six months after the initialvisit, patients were invited to return to thepharmacy to provide another blood sample toevaluate any reduction in LDL level. Patientswere also asked to complete a satisfactionquestionnaire. Results of this trial demonstratedan increase in the compliance rate from 40% to60%, representing a 50% improvement incompliance. In addition, LDL levels werereduced by approximately 15 mg/dl.

A similar study recently published in the

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Figure 1. Trials and pooled analysis showing a 16% reduction in coronary death or myocardial infarction in patients whoachieved low-density lipoprotein levels of approximately 75 mg/dl. CI = confidence interval; std = standard; PROVEIT–TIMI 22 = Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22, A toZ = Aggrastat-to-Zocor, TNT = Treating to New Targets, IDEAL = Incremental Decrease in End Points Through Aggressive LipidLowering; OR = odds ratio. (From reference 12 with permission.)

ROLE OF THE PHARMACIST Bottorff

pharmacology literature was a prospective trial of50 patients to whom a lipid-lowering drug wasnewly prescribed.15 Patients received individu-alized counseling in three visits with apharmacist over 3 months. At the first visit, theyreceived education about cholesterol, thecardiovascular risk of having high cholesterollevels, dietary interventions, the role and use oflipid-lowering drugs, and the potential adverseeffects of the drug. At the second visit, their lipidprofile and compliance were assessed, and thebaseline message was reinforced. Finally, at thethird visit, their lipid profile and compliancewere reassessed. To enable comparison of theresults with usual and customary practices, acontrol group was established. The controlgroup received routine counseling about thedosages of the drugs they were taking and aboutthe indications for therapy. Compared with thecontrol group, patients who received individu-alized counseling increased compliance from40% to almost 80%. In addition, the number ofpatients who achieved LDL treatment goals was60% in the control group and 80% in theintervention group.

Pharmacists’ Role in Diabetes Management

Just as the pharmacist’s role in managingdyslipidemia has been proven, the publishedliterature documents the key role pharmacistsplay in the care of patients with type 2 diabetesmellitus. One example is a study that wasconducted to assess hemoglobin A1c values,blood pressure, lipid levels, and aspirin use atbaseline and at 1 year in 191 patients withdiabetes.16 The most notable result was notblood pressure or LDL level reduction but thedoubling of the number of patients who weretaking aspirin, as is recommended for patientswith diabetes. Even more important than thisfinding was the reduction in hemoglobin A1cvalues from 9.5% at baseline to 7.8% at 1 year.

Researchers in another study recently reportedon the relative importance of drug therapycompared with lifestyle modification and on therelationship of each in reducing cardiometabolicrisk factors.17 Table 2 summarizes their findings.

Of interest was the large decrease in estimatedmortality as a result of dietary changes. Is therisk reduction associated with dietary changes aresult of weight loss, or is it specifically the effectof weight loss on various cardiometabolic riskfactors related to cholesterol, high-densitylipoprotein cholesterol, and triglyceride levels;

blood pressure; and glucose control? Forpharmacists, the proof is here. The pharmacists’role in counseling patients regarding lifestylemodifications in addition to drug therapy iscritical.

Pharmacists’ Role in Drug Therapy Management

Drug therapy management programsoriginated from the Medicare Modernization Act,which also implemented the Medicare Part Dprescription drug benefit for the elderly.18–20 Thegoal of such programs is to optimize patienttherapeutic outcomes and to improve the long-term health of Medicare beneficiaries.18, 19 Drugtherapy management programs allow pharmaciststo conduct utilization reviews to examine thedrugs patients are taking to ensure that dosagesare correct and that durations of therapy areappropriate. In these programs, pharmacists canalso explain the proper way to take drugs, andthey allow beneficiaries to ask questions andreceive feedback from the pharmacist in private.19

The American Association of Colleges ofPharmacy developed a list of services that shouldbe included in all drug therapy managementprograms18:

• Assess the patient’s health status.• Formulate a drug treatment plan.• Select, start, modify, or administer drug

therapy.• Monitor and evaluate the patient’s response

to therapy.• Perform a comprehensive drug review to

identify, resolve, and prevent drug-relatedproblems.

• Document the care delivered and communicateessential information.

• Provide verbal education and training.• Provide information, support services, and

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Table 2. Approximate Mortality Reduction Potential ofInterventions for Coronary Artery Disease17

Reduction inMortality Risk

Intervention (%)Low-dose aspirin 18Moderate alcohol intake 20Statins 21b-Blockers 23Physical activity 25ACE inhibitors 26Smoking cessation 35Combined dietary changes 45ACE = angiotensin-converting enzyme.

Supplement to PHARMACOTHERAPY Volume 26, Number 12, 2006

resources designed to enhance patientadherence.

• Coordinate and integrate drug therapymanagement services.

In addition, the American PharmacistsAssociation has made available a monographabout drug therapy management programs andthe role of pharmacists.21 Drug therapy manage-ment programs are comprehensive ways toreview and implement medical treatment in theelderly population. Pharmacists will play acrucial role in development implementation andmaintenance of such programs.

Conclusion

Patients with cardiometabolic risk factors havecomplex conditions, and they are at high risk andare undertreated. Numerous opportunities existfor pharmacists to recognize and recommendtreatment for cardiometabolic risk factors andimprove compliance, regardless of their practiceenvironment. New therapies for obesity mayreduce the overall risk for cardiovascular diseaseand decrease the requirement for additionaldrugs. However, pharmacists are still an integralpart of overall risk management. Pharmacistscan educate practitioners and counsel patientsabout lifestyle modification and compliance. Bydoing so, they can accomplish the most importantcomponent of risk reduction with the fewestdrugs and health care and economic resources.

Acknowledgment

The author would like to acknowledge thecontributions of Robyn Graham, Pharm.D., foreditorial assistance in the preparation of themanuscript.

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