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Therapy for Stable CAD:Is the Pill as Mighty as the Balloon?

Article

More than1.8 millioncardiaccatheterizationsandat least 600,000 percutaneoustransluminal coronaryangioplasty (PTCA)procedures are performedin the United States annually.1 The use of these diagnosticand interventionalmodalities continues togrow even as financial constraintsincrease. Yet formany patients with coronaryartery disease (CAD),medical therapy may be anappropriate option.

More than1.8 millioncardiaccatheterizationsandat least 600,000 percutaneoustransluminal coronaryangioplasty (PTCA)procedures are performedin the United States annually.1 The use of these diagnosticand interventionalmodalities continues togrow even as financial constraintsincrease. Yet formany patients with coronaryartery disease (CAD),medical therapy may be anappropriate option.

THE EVIDENCE FORMEDICAL THERAPY
Studies suggest thatmedical treatment is at leastas beneficial as PTCA in patientswith low-risk stableCAD. The American Collegeof Cardiology/AmericanHeart Associationguidelines recommend thatmedical therapy be consideredbefore PTCA in low riskpatients or those withmild to moderate angina.2Low-risk patients are thosewho have 1 or 2 major coronaryarteries with morethan 50% stenosis, relativelynormal left ventricular function(ejection fraction, 40%or higher), and mild tomoderate anginal symptoms.Although PTCA mayprovide faster relief fromanginal symptoms, no publishedevidence demonstratesthat it increases survivalor lessens the risk ofacute myocardial infarction(MI) more than optimalmedical management inthese patients.

Duke Databank study. A 6-year study publishedin 1994 examineddata from more than 9000patients with symptomaticCAD who were referred forcardiac catheterization.3Thirty percent underwentPTCA, 37% had coronaryartery bypass graft surgery,and 33% received unspecifiedmedical therapy.As expected, the survivalbenefit of revascularizationwas greater in patients withmore severe disease. However,no survival benefitwas seen for revascularizationcompared with medicaltherapy for those with1-vessel CAD or less severe2-vessel disease, despitethe fact that medical therapywas far from optimal bycurrent standards.

The second RandomizedIntervention Treatmentof Angina (RITA-2)trial. In this study, improvementin anginal symptomswas demonstrated after eitherPTCA or unspecifiedmedical therapy in 1018 patientswith CAD, but PTCAwas associated with a greaterrisk of mortality (P 4

The Atorvastatin VersusRevascularizationTreatment (AVERT) study.This trial demonstrated thataggressive lipid loweringwas associated with agreater reduction in ischemicevents than PTCA inselect patients with stableCAD.5The participantswere 341 patients withasymptomatic or mild tomoderate angina, relativelynormal left ventricular function,and a low-densitylipoprotein (LDL) cholesterollevel of at least 115mg/dL, who were initiallyreferred for PTCA. Theywere randomized to PTCAor atorvastatin, 80 mg/d.After 18 months of followup,the atorvastatin grouphad 36% fewer ischemicevents than the PTCAgroup (P = .048), a differencethat was not consideredstatistically significantafter an adjustment for interimanalyses. However, asignificantly longer time tothe first ischemic event wasnoted in patients in the atorvastatingroup (P = .03).

Bypass grafting study.A recent study examinedthe comparative survivalbenefits of PTCA, left internalmammary artery by-pass grafting, and unspecifiedmedical therapy in 1188patients who presented withproximal 1-vessel CAD duringa 9-year period.6 In thisretrospective analysis ofprospectively collected data,patients were followed for5.7 years. Interventionaltherapy yielded no significantmortality benefit overmedical therapy, despite thefact that more patients inthe medical therapy grouphad previous congestiveheart failure, previous acuteMI, and long-term anginalsymptoms.

WHAT CONSTITUTESOPTIMAL MEDICALTHERAPY?
Aggressive medicaltreatment includes strategiesto control modifiable riskfactors.7such as statin therapy(Box) to reduce LDL cholesterollevels-the primarytarget of lipid-lowering interventionsaccording to theNational Cholesterol EducationProgram (NCEP) guidelines.8 These guidelines recommendthat all patientswith CAD aim for an LDLcholesterol level of less than100 mg/dL. The ongoingTreating to New Targets(TNT) trial, which is followingCAD patients who aretaking atorvastatin, 10 mg/dor 80 mg/d, to achieve anLDL cholesterol level of100 mg/dL or 75 mg/dL, respectively,will demonstratewhether aggressive LDLlowering to well below100 mg/dL will further reducecardiovascular risk.9

Appropriate medicaltherapy also includes aspirinand, as needed, angiotensinconvertingenzyme inhibitors,calcium channel blockers,angiotensin II receptorblockers, β-blockers, and nitrates.Lifestyle modification-including smoking cessation,dietary changes,weight reduction, and exercise-and control of bloodpressure and diabetesshould be offered as an alternativeto PTCA, at least for atrial period long enough toallow for control of these factors.Patients who do notachieve the desired resultswith a combination oflifestyle modification andmedical therapy can then undergoPTCA for symptomcontrol if warranted.

References:

REFERENCES:1. American Heart Association. 2002Heart and Stroke Statistical Update. Dallas:American Heart Association; 2001.
2. Smith SC Jr, Dove JT, Jacobs AK, etal. ACC/AHA guidelines for percutaneouscoronary intervention (revisionof the 1993 PTCA guidelines)-executivesummary. Circulation. 2001;103:3019-3041.
3. Califf RM, Mark DB. Percutaneousintervention, surgery, and medicaltherapy: a perspective from the DukeDatabank for Cardiovascular Diseases.Semin Thorac Cardiovasc Surg.1994;6:120-128.
4. RITA-2 Trial Participants. Coronaryangioplasty versus medical therapy forangina: the second Randomised InterventionTreatment of Angina (RITA-2)trial. Lancet. 1997;350:461-468.
5. Pitt B, Waters D, Brown WV, et al.Aggressive lipid-lowering therapy comparedwith angioplasty in stable coronaryartery disease. N Engl J Med.1999;341:70-76.
6. Greenbaum AB, Califf RM, JonesRH, et al. Comparison of medicinealone, coronary angioplasty, and leftinternal mammary artery-coronaryartery bypass for one-vessel proximalleft anterior descending coronaryartery disease. Am J Cardiol.2000;86:1322-1326.
7. Blumenthal RS, Cohn G, SchulmanSP. Medical therapy versus coronaryartery angioplasty in stable coronaryartery disease: a critical review of theliterature. J Am Coll Cardiol. 2000;36:668-673.
8. Expert Panel on Detection, Evaluation,and Treatment of High Blood Cholesterolin Adults. Executive summary ofthe Third Report of the National CholesterolEducation Program (NCEP) ExpertPanel on Detection, Evaluation, andTreatment of High Blood Cholesterol inAdults (Adult Treatment Panel III).JAMA. 2001;285:2486-2497.
9. LaRosa JC, for the TNT SteeringCommittee. Effect of lowering LDL-Cbeyond currently recommended minimumtargets: the Treating to New Targets(TNT) study. In: XIII InternationalSymposium on Drugs Affecting Lipid Metabolism.Abstract Book. Houston: GiovanniLorenzini Medical Foundation;1998:65.
10. Davignon J. Methods and endpointissues in clinical development oflipid-acting agents with pleiotropic effects.Am J Cardiol. 1998;81:17F-24F.
11. Horne BD, Muhlstein JB,Carlquist JF, et al. Statin therapy, lipidlevels, C-reactive protein and the survivalof patients with angiographicallysevere coronary artery disease. J AmColl Cardiol. 2000;36:1774-1780.

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