News You Can Use: Strategies to Lower Cardiovascular Risk: What the Latest Evidence Shows

September 2, 2004
David T. Nash, MD
David T. Nash, MD

Despite the manydouble-blind,placebo-controlledtrials thathave demonstratedthe efficacy of statins inreducing the risk of cardiovascularevents, a largenumber of patients who aretreated with these drugsstill experience suchevents. This may be becausepatients who requireintensive lipid lowering arenot receiving adequatedosages of statins.

Despite the manydouble-blind,placebo-controlledtrials thathave demonstratedthe efficacy of statins inreducing the risk of cardiovascularevents, a largenumber of patients who aretreated with these drugsstill experience suchevents. This may be becausepatients who requireintensive lipid lowering arenot receiving adequatedosages of statins.

Here I report on recentstudy results that illustratethe problem of undertreatment.I also discussevidence that greater decreasesin low-density lipoproteincholesterol (LDLC)levels are associatedwith greater reductions inthe incidence of cardiovascularevents. In addition, Ipresent the results of studiesof novel therapies thatmay someday reduce thetoll of coronary events(Box).

UNDERTREATMENT:A COMMONPROBLEM

In a study by Jnssonand colleagues,1 a total of9789 patients were givenlipid-lowering therapy for 10 years. During the firstyear of treatment, only 5%of patients were titrated toa higher dose; overall, 70%of the patients did not attainlipid goals. Those whodid reach their goals experiencedfewer events andincurred lower health carecosts.

Herbert and associates2reported that a significantnumber of patientswith documented coronaryartery disease are not givenlipid-lowering drugs at all.In an analysis of 6914 patientswho underwent coronaryartery bypass graftingbetween January 2000 andJuly 2003, only 32% of patients who received 2 typesof cardiovascular drugs ondischarge were given a lipid-lowering agent as one oftheir 2 medications.2

EVIDENCE THAT“LOWER IS BETTER”

The REVERSingAtherosclerosis with AggressiveLipid Lowering(REVERSAL) study, whichincluded 502 patients withstable coronary artery disease(CAD), demonstratedthat atorvastatin, 80 mg/d,provided greater LDL-Creduction than pravastatin,40 mg/d; this greater decreasewas associated withless progression of CAD as measured by intravascularultrasonography.3

The Pravastatin orAtorvastatin Evaluation andInfection Therapy-Thrombolysisin Myocardial Infarction22 (PROVE-IT)trial compared intensive(atorvastatin, 80 mg/d) andmore moderate (pravastatin,40 mg/d) lipid-loweringtherapy in 4162 patientshospitalized at major USmedical centers for anacute coronary syndrome.After a mean follow-up of2 years, intensive statintreatment had loweredLDL-C levels to a median of 62 mg/dL, compared witha median of 95 mg/dL withstandard lipid lowering(P 4 Patients whoreceived the intensive lipidloweringregimen experienceda 16% greater reductionin risk of death ormajor cardiovascularevents than those who receivedmoderate lipid-loweringtherapy (P = .005).4Interestingly, more thanhalf of the patients enrolledin the trial had preexistingCAD, diabetes mellitus, orperipheral vascular disease--all of which aremajor indications for statintherapy--but only 25% ofthe patients in the trialwere receiving statin therapyat baseline.

Taken together, theREVERSAL and PROVE-ITtrials foreshadowed an increasedawareness of theneed for appropriate butaggressive lipid-loweringtherapy. An LDL-C goal ofless than 70 mg/dL wasproposed as a therapeuticoption in very high-risk patients in a recent update tothe National CholesterolEducation Program AdultTreatment Panel III guidelines.5 However, there isinsufficient evidence to recommendthis treatmentgoal in less high-riskpatients.

The results of theTreating to New Targets(TNT) trial, which are expectedto be reported at theNovember 2004 meeting ofthe American Heart Association,will help expertsreach a definite decisionabout changing the guidelinesfor this larger patientpopulation. The TNT trialhas randomized 10,003 patientsto double-blind treatmentwith either atorvastatin,10 mg, or atorvastatin,80 mg; the average followupis 5 years.6 In the meantime,practitioners are advisedto focus on helpingpatients achieve an LDL-Clevel of 100 mg/dL orlower. Fewer than 50% of allpatients who have had anacute myocardial infarctioncurrently reach this goal,which indicates that bettercompliance is needed.

OPTIONS FORAGGRESSIVE LIPIDLOWERING

To meet the need formore aggressive lipid-loweringtherapy, the neweststatin, rosuvastatin, mightbe used. There is evidencethat rosuvastatin is themost efficacious for loweringtotal cholesterol, LDLC,and non-high-densitylipoprotein cholesterol.7 Arandomized, parallel-group,open-label trial compared rosuvastatin with 3 othercurrently marketed statinsand demonstrated that rosuvastatin,10 to 40 mg/d,produced LDL-C reductionsranging from 46% to55%, compared with reductionsof 37% to 51% foratorvastatin, 10 to 80 mg/d;28% to 46% for simvastatin,10 to 80 mg/d; and 20%to 30% for pravastatin, 10 to40 mg/d.8

Combination therapythat includes fibrates, niacin,and/or ezetimibe in additionto a statin can sometimesbe helpful as well.Significant results can alsobe achieved with the additionof such nonpharmacologictherapies as solublefiber, stanol-ester margarine,and sterol-enrichedorange juice.