Need for a Paradigm Shift: TheImportance of Risk Factor ReductionTherapy in Treating Patients with

Cardiovascular DiseaseSidney C. Smith, Jr., MD

Cardiovascular disease remains the number one killer inthe United States, despite advances made in diagnosisand therapy. A major shift to expand treatment beyondsymptomatic obstructions and infarctions toward com-prehensive therapies aimed at treatment of the underly-ing disease process could decrease the death rate andcost of cardiovascular disease enormously. In the past 5years, major trials have clearly demonstrated that ag-gressive intervention with lipid-lowering therapy candramatically alter the course of disease. Aspirin, smok-

ing cessation, exercise, diet, and other medical andlifestyle interventions can also decrease risk. Successfultherapies are not being implemented, however. Makingprevention the primary approach to treatment will re-quire increased resource allocation, use of health pro-vider teams, integration of healthcare delivery systems,and expanded emphasis on educating patients aboutprevention. Q1998 by Excerpta Medica, Inc.

Am J Cardiol 1998;82:10T–13T

Cardiovascular disease remains the number onekiller in the United States. Coronary artery disease

kills about 500,000 men and women each year, andstroke claims the lives of another 140,000 annually.An additional 1 million people survive heart attackseach year.1 Diseases of the heart and blood vesselshave been a concern of medicine, science, and societyfor decades. However, the problem has reached epi-demic proportions. One US citizen dies of cardiovas-cular disease about every 30 seconds. Clearly, the timehas come for a re-evaluation of conventional philos-ophies and approaches to the management of cardio-vascular diseases.

Over the past decade, advances in diagnosis, im-aging, medical therapy, and interventional procedureshave greatly improved care for heart disease andstroke. However, these advances, combined with theoverall disease burden, have resulted in a huge health-care bill. More than $150 billion a year is spent on thetreatment of heart disease in the United States. Thecost is expected to surpass $200 billion annually bythe year 2000.1 Closer inspection of these expendi-tures shows that only 6 cents of every dollar goestoward efforts to treat the disease medically and toencourage healthier lifestyles. By far, the largest con-tributor to the upward cost spiral is hospitalization andrelated services.

The development and refinement of surgical andinterventional techniques have unquestionably playeda major role in the treatment of cardiovascular dis-eases. Each year, nearly 1 million people in the UnitedStates undergo coronary bypass surgery or other cor-onary interventions, such as balloon angioplasty.1

However, these techniques and procedures are tar-geted to relieve symptoms and do not address theunderlying cause of the problem.

Research in vascular and molecular biology hasproduced a new understanding about the origin andevolution of coronary obstructions. Angiographicstudies have shown that most cases of myocardialinfarction (MI) are associated with vascular obstruc-tions of ,70%.2 In fact, a subset of high-risk, less-occlusive lesions has been identified as a major factorin the occurrence of MI and other acute coronarysyndromes.3 Initially, these high-risk lesions expandoutward, causing minimal obstruction, are often inareas lacking collateral circulation, and are usuallyasymptomatic.4 Histologically, high-risk plaques havea thin, fibrous cap and a large underlying lipid pool.Plaque rupture usually occurs at the margin and isrelated to a number of factors, including inflammation,suppression of collagen synthesis, and collagen break-down.5,6

Our improved understanding of the medical anddietary therapy for coronary atherosclerosis offers theopportunity for a more aggressive approach to preven-tion. Such an approach would lead to a clinical para-digm shift, away from treatment of obstructions andinfarctions and toward treatment of the underlyingdisease process.

LIPID-LOWERING THERAPY PROVESITS WORTH

Therapy that lowers cholesterol by 20% signifi-cantly decreases cardiovascular events within 1–2years. By comparison, the associated changes inplaque stenosis with lipid-lowering therapy are mini-mal, on the order of 1–2%.7 Treatment-related plaqueregression or retardation of the rate of progressioncannot entirely explain the observed reduction inevents or improved outcome. Stabilization of the high-risk plaques is a more likely explanation for the rapid

From the Division of Cardiology and the Academic Center for Cardio-vascular Disease, University of North Carolina, Chapel Hill, NorthCarolina.

Address for reprints: Sidney C. Smith, Jr., MD, Division of Cardi-ology, CB #7075, Burnett-Womack, University of North Carolina,Chapel Hill, North Carolina 27599-7075.

10T ©1998 by Excerpta Medica, Inc. 0002-9149/98/$19.00All rights reserved. PII 0002-9149(98)00716-4

and impressive reduction in the event rate.7–9 Treat-ment to alter certain coronary risk factors also tends tocorrect endothelial dysfunction that occurs early in theevolution of coronary atherosclerosis. Low-density li-poprotein (LDL) reduction is among the factors thatlead to improved endothelial function.

Early trials of lipid-lowering therapy demonstrateda reduction in cardiovascular events, but the trialslacked the statistical power to show that lipid loweringcould decrease total mortality. The tide began to turnwith completion of the Scandinavian Simvastatin Sur-vival Study (4S).10 The 4S trial resolved the debateabout the mortality benefits of lipid lowering by show-ing a 30% reduction in total mortality and 42% reduc-tion in coronary mortality over 5 years among 4,444patients with coronary artery disease. The benefitsbegan to emerge early, after just 1–2 years of therapy.Importantly, 4S patients treated with lipid-loweringtherapy had a 35–40% reduction in the need for cor-onary bypass surgery and interventional procedures.

Several other key studies conducted throughout theworld have added to the body of evidence that aggres-sive preventive intervention with lipid-lowering ther-apy can dramatically alter the clinical course of cor-onary atherosclerosis. The 4S study involved patientswhose total cholesterol level averaged about 260 mg/dL. However, the average cholesterol level in typicalUS MI patients is about 210 mg/dL. The Cholesteroland Recurrent Events (CARE) trial11 demonstratedthat lipid-lowering therapy can favorably affect out-come in patients whose cholesterol levels resemblethose of the typical US heart attack patient.

The CARE trial involved post-MI patients whosemean cholesterol level was 209 mg/dL. Patientstreated with lipid-lowering therapy had approximatelya 25% reduction in the incidence of nonfatal MI andcoronary death. The need for coronary interventionsdeclined by a similar degree, and stroke incidence was.30% lower in patients who received lipid-loweringtherapy. Notably, the benefits spanned a wide range ofpatient subgroups, including women and elderly pa-tients. Just as in 4S, the benefits of treatment in theCARE trial emerged within 2 years.

The Postcoronary Artery Bypass Graft (Post-CABG) trial12 examined the potential benefits of lipid-lowering therapy from a different perspective. Specif-ically, the trial sought to compare the outcomes afterCABG between aggressive lipid lowering to LDLlevels of about 95 mg/dL versus more conservativelipid lowering to LDL levels of about 135 mg/dL.Would bypass grafts be more likely to remain diseasefree with more aggressive lipid-lowering therapy? Thetrial provided a strong affirmative answer. The bene-fits of treatment became apparent within 2–3 yearsafter starting lipid-lowering therapy.

The previous trials involved patients who had ahistory of MI. The next logical question was whethertreatment with a lipid-lowering agent would favorablyalter the clinical course in patients who have elevatedcholesterol levels but no evidence of coronary athero-sclerosis. The West of Scotland Coronary Prevention(WOSCOPS) Study13 addressed the issue and pro-

vided another affirmative answer. Patients treated withpravastatin had a 31% reduction in nonfatal MI, 32%reduction in cardiovascular mortality, and a 22% re-duction in all-cause mortality. The difference began toemerge within the first year of treatment.

Collectively, the 4 studies described above leaveno room for doubt about the value of lipid-loweringtherapy. Moreover, they are not the only studies todemonstrate impressive benefits of lipid-loweringtherapy. The overwhelming burden of proof favorsearly, aggressive intervention to decrease cholesterollevels. An early preventive strategy can prevent cor-onary events, save lives, and decrease the need forbypass surgery and other coronary interventions.

Certainly, lipid-lowering therapy is not the onlypreventive intervention that can favorably alter thecourse of cardiovascular disease. Use of angiotensin-converting enzyme (ACE) inhibitors after MI has beenshown to decrease total mortality, cardiovascular mor-tality, recurrent hospitalization, and recurrent MI.14,15

Aspirin, smoking cessation, exercise, diet, and othermedical and lifestyle interventions also can contributeto risk reduction. The cumulative potential benefits ofthe recent lipid-lowering trials prompted 2 Nobel lau-reates to predict an end to heart attacks by the year2000, assuming widespread adoption of available pre-ventive strategies.16

SUCCESSFUL STRATEGIES REMAINUNIMPLEMENTED

Unfortunately, most patients who could benefitfrom therapies to decrease cardiovascular risk do notreceive them. Data from the Cooperative Cardiovas-cular Project17 provided a revealing, if disappointing,picture. About three-fourths of Medicare MI patientswho entered hospitals as smokers did not receiveinstruction in smoking cessation. Fewer than half re-ceivedb blockers. Almost one-quarter did not leavethe hospital on an aspirin regimen. Other studies in-dicate that,20% of patients with hypercholesterol-emia and coronary artery disease are on lipid-loweringagents at hospitalization, and 2 years later, only one-third of patients are treated with lipid-lowering ther-apy.

Therapies that could make a profound difference inpatient outcome are not being used. Why? At least 4major factors contribute to the problem:

• Lack of agreement among physicians. Cliniciansinvolved in the management of patients at risk forcardiovascular disease and its consequences mustmove forward to establish guidelines and use therapiesthat decrease the risk of cardiovascular events.

• Failure to implement proven strategies. All toooften, clinical studies provide conclusive evidence,but physicians do not prescribe the therapies for theinpatients.

• Poor patient compliance. After receiving pre-scriptions and instructions for proven therapies, manypatients never begin therapy, or they discontinue with-out consulting their physicians.

• Lack of reimbursement for risk-reducing thera-pies. Third-party payors must pay for preventive ther-

A SYMPOSIUM ON CHOLESTEROL AND CORONARY DISEASE 11T

apies. There is no justification for a delivery andreimbursement system that will pay for expensiverevascularization procedures but not for preventivetherapies such as smoking cessation counseling orlipid-lowering therapy, which can decrease subse-quent cardiovascular events and prolong life.

ORGANIZATIONS TACKLE RISKREDUCTION

The approach to management of cardiovascularrisk must change. The American Heart Association(AHA) and American College of Cardiology (ACC)have taken a step toward encouraging that change.The 2 organizations have jointly and publicly en-dorsed prevention strategies for cardiovascular dis-ease.18 The AHA and ACC agree that “Compellingscientific evidence…demonstrates that comprehensiverisk factor interventions extend overall survival, im-prove quality of life, decrease need for interventionalprocedures such as angioplasty and bypass grafting,and decrease the incidence of subsequent MI.” The 2organizations cite 9 proven strategies, which theycharacterize as a “Guide to Comprehensive Risk Re-duction for Patients With Coronary and Other Vascu-lar Diseases.”18 The strategies covered in the docu-ment are smoking cessation, lipid management, phys-ical activity, weight management, antiplatelet/anticoagulant agents, use of ACE inhibitors inpost-MI patients, appropriate use ofb blockers, estro-gen replacement therapy, and blood pressure control.

The consensus statement provides clinicians andpatients with a blueprint for cardiovascular risk reduc-tion. The blueprint emphasizes lifestyle modificationand medical therapy for all patients who have coro-nary and vascular disease. Whether a physicianchooses 2, 3, or all 9 strategies for a given patient,implementation will make a difference in the patient’sclinical course and possibly the patient’s life. Even asingle intervention can make a difference. Considersmoking cessation. Cigarettes play a role in 80% of allcardiovascular mortality in patients,50 years of age.The United States accounts for only 5% of the world’swomen; yet, half the tobacco-related mortality inwomen occurs in the United States. Smoking cessa-tion alone can decrease cardiovascular mortality by40%.1,19–22

Antiplatelet agents can have a profound impact onthe prevention of acute coronary syndromes. Patientswho take aspirin regularly have been shown to have a72% reduction in the odds ratio for MI.23 Beta-blockertherapy can decrease mortality after MI by at least20%.24 About 60 million people in the United Stateshave hypertension, but almost 80% receive inadequatetreatment, leaving them at greatly increased risk ofstroke and heart disease.1 Physical activity and weightmanagement represent cost-effective lifestyle changesthat can decrease cardiovascular risk.

The AHA is tackling another obstacle to risk re-duction through a task force that is evaluating strate-gies to improve patient adherence. Currently, half ofall patients prescribed risk-reducing therapies discon-tinue use within 1 year.25–28 One way to improve

adherence is through case management by nurses. Theapproach involves nurses and physicians working witha team of health professionals to manage hypertensionand diabetes, achieve smoking cessation, and imple-ment other risk-reducing therapies. In the StanfordCardiac Rehabilitation program, compliance with thenurse case management approach was 90% at 1 year,compared with 20% with usual care.29

PROGRESS IN REIMBURSEMENTSome progress is also being made with respect to

reimbursement for delivering preventive therapies.Several of the nation’s largest managed care compa-nies have met with the AHA to begin a discussion ofreimbursement for cardiovascular prevention. The im-petus for the discussion has been quality, not cost.Managed care companies have a vested interest inshowing that their programs are superior to others.The AHA has worked with the companies to identifyprevention activities that mesh with the quality assess-ment measures by which managed care companies areevaluated. Companies that do not excel in these areasof cardiovascular prevention could find themselves ata competitive disadvantage.

A TIME FOR ACTIONWhen trying to move forward, a look back at the

past often proves useful. In the case of cardiovasculardisease, history can provide important direction forthe future. The AHA held its first meeting in 1925.Only 200 people attended the meeting, and 10 presen-tations were made.30 However, that modest programclearly reflected the concerns of that day’s cardiovas-cular clinician, and the issues they addressed are sim-ilar to those that confront us today. The first 4 presen-tations, in particular, stand out: (1) an official messagefor decreasing heart disease; (2) the care of adults withmoderate heart disorders; (3) economic aspects ofheart disease; and (4) what can the AHA accomplish?

As the titles of those presentations indicate, thenature of the problem and the essential concerns havechanged little in 70-plus years. What has changed isthe dimension of the problem, which has reachedepidemic proportions in the United States.

Superb advances have occurred in the treatment ofcoronary artery obstruction, but those advances areinsufficient to stem the tide of the growing epidemic.Bypassing symptomatic obstructions or treating acuteinfarctions is not enough. The time for change is pastdue. A meaningful impact on cardiovascular diseaserequires a concerted effort to make prevention theprimary approach to the disease processes. The effortrequires increased resource allocation, use of healthprovider teams, integration of healthcare delivery sys-tems, and expanded emphasis on prevention educa-tion. The scientific advances that provide a soundclinical and scientific basis for prevention must findtheir way from the benchtop to the bedside.

The field of cardiovascular medicine has neverfaced a more important challenge. The field also hasnever been better prepared with the tools necessary totake on such a challenge. The innovation, skill, and

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determination that have fueled a clinical success inacute care and cardiovascular intervention must nowbe applied to risk-reducing therapies. Only by meansof the same commitment to provide the best carepossible for patients can the goal of decreasing theburden of cardiovascular disease be achieved.

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