Cardiovascular disease (CVD) is stillunchallenged as the number onekiller in the United States as it hasbeen for virtually the entire past century,and the link between CVD and dyslipidemiais well established.1 In particular, attentionhas focused on elevations in low-densitylipoprotein cholesterol (LDL-C) as the lipidabnormality most directly implicated as arisk factor for CVD.
The most effective drugs for reducingLDL-C, and thereby reducing the risk ofCVD, are the 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins),which act by blocking the hepatic synthesisof cholesterol. Accordingly, statins now comprisethe largest drug category by dollar volumein the United States ($16 billion in2005) and the second largest category bynumber of dispensed prescriptions (144 millionin 2005).2
The success of the statins has led to areconsideration of therapeutic goals andmeans of achieving them, for the statins permitreduction of LDL-C to levels previouslyunattainable. In turn, this expanded vista oftherapeutic possibilities has led to questionsabout the optimal utilization of statins. Howshould individual products of this class beselected for individual patients? What arethe risks associated with statin therapy, andhow do these risks differ among the individualstatins? How should statins be used inpatients at the highest risk of CVD? What isthe most cost-effective means of using thestatins?
Journal of Managed Care
With strategies for the management ofCVD and optimal utilization of statins at acrossroads, this supplement to brings together 3special reports of timely interest. In "AnAssessment of Statin Safety," James M.McKenney, PharmD, addresses the concernsabout safety with statins. Since 2001, whencerivastatin was withdrawn from the marketfor reasons of safety, some nonprofessionalsources have called the statins "dangerousdrugs." However, analysis of data from theprofessional literature and adverse eventreports offer a different picture. Summarizingthe findings of the National LipidAssociation Statin Safety Assessment TaskForce, Dr McKenney places the risk ofmyopathy in a realistic perspective. The riskvaries among the statins and is clearly associatedwith dose and exposure. At approveddosages, the risk of serious myopathy(including rhabdomyolysis) is well underhalf of 1%; most cases of serious myopathyhave been associated with pharmacokineticinteractions with drugs that retard statinmetabolism. Among other perceived safetyconcerns, liver failure is considered aremote risk; proteinuria occurs with allstatins but is not associated with anyincreased risk of renal failure; and there isno evidence to support concerns about neurotoxicityand cognitive impairment withstatin therapy.
Robert M. Guthrie, MD, offers a cogentoverview in "Rising to the Challenge ofTreating High-risk Patients" of severalimportant recent clinical trials involvingaggressive statin therapy in patients at highrisk of CVD. Several conditions placepatients at high risk: diabetes, known coronaryheart disease, noncardiac atherosclerosis,abdominal aneurysm, and the metabolicsyndrome (a common condition in olderpatients, characterized by central obesity,insulin resistance, glucose intolerance,hypertension, and dyslipidemia).3 Whereasthe standard goal for LDL-C correction is100 mg/dL or less, patients at very high riskfor CVD may benefit from a more aggressivelipid-lowering regimen aimed at achievingLDL-C concentrations of 70 mg/dL or less.The conclusion from a number of importantclinical trials utilizing high-dose statins isthat the lower LDL-C goal is achievable andis associated with significantly reduced riskof cardiovascular events and mortality.
Given the proven ability of statins toreduce CVD risk (and its estimated $400-billion price tag in 20061), questions aboutcost-effectiveness involve the choice ofstatin rather than the rationale for statintherapy. As reviewed by Terrance Killilea,PharmD, and Lori Funk, PharmD, in "CostEfficiency and Formulary Considerations forStatin Therapy," cost analyses focus onachieving target LDL-C levels at the lowestmedical and pharmaceutical costs. Theoverall cost of therapy is generally expectedto become more affordable as older agents gooff patent. However, differences in potencytranslate to different treatment costs associatedwith achieving moderate versus largereductions in LDL-C. For patients at moderaterisk, for whom the target reduction inLDL-C concentration is up to 40%, any ofthe statins will be effective, and generic versionscan be used. However, for patients athigher risk, who require greater reductionsin LDL-C, the greatest cost-effectivenessmay be seen with rosuvastatin or with afixed combination of simvastatin and thecholesterol-absorption blocker ezetimibe.
Questions still remain about individualizationof statin therapy—which drug atwhat dosage? There is no question, however,that for now and the foreseeable future,statins will continue to play a key role inreducing the immense human and economicburden of CVD.
1. American Heart Association. Heart Disease and Stroke Statistics—2006 Update. 2006;113:85-151.
2. IMS Health. IMS National Sales Perspectives, February 2006. Available at: www.imshealth.com. Accessed September 16, 2006.
3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel onDetection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 2001;285:2486-2497.