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...DIABETES MANAGEMENT

Statin therapy works for patients who have type 2 diabetes

Kenneth E. Korber, PA, PhD(c)

Kenneth Korber is a clinical associate in cardiology at the University of Illinois College of Medicine, Chicago, and a Fellow within the Association of PAs in Cardiology. He has indicated no relationships to disclose relating to the content of this article.

Coronary heart disease (CHD) remains the leading cause of death in the United States, resulting in more deaths per year than the next five leading causes of death combined.¹ Although prevention and intervention efforts have been lowering the CHD mortality rate, clinical progress is being undercut by rising rates of obesity and type 2 diabetes mellitus (DM), as well as by reduced adherence to evidence-based prevention efforts by caregivers. Statin therapy—coupled with lifestyle changes such as a heart-healthy diet, weight loss, and exercise—has been shown to be effective at reducing cholesterol levels in patients with established cardiovascular disease. Statins have helped to reduce morbidity and mortality in this patient group, but one question has remained: Can statins achieve an equivalent effect in persons with type 2 DM?

DIABETES IMPERILS THE HEART

Type 2 DM increases the levels of metabolic stress hormones and peptides; in turn, these higher levels increase platelet aggregation, decrease tissue plasminogen activator activity, and increase plasminogen activator inhibitor levels. These detrimental microvascular changes, if left unchecked, will eventually lead to acidosis, cellular injury, and myocardial cell death. Once myocardial tissue damage occurs, MI can follow, and muscle necrosis will produce dysfunction in a small or large portion of the heart muscle. And if the heart has to pump oxygenated blood with only a fraction of its ventricle alive, chest pain, heart failure, and life-threatening arrhythmias can occur.²

STATIN STUDY PROVIDES HOPE

Published in 2004 with a follow-up article this year, the Collaborative AtoRvastatin Diabetes Study (CARDS) was a multicenter, prospective, randomized controlled trial. The cohort included patients with type 2 DM and one additional cardiovascular disease risk factor who were given placebo therapy or an oral statin (atorvastatin, 10 mg/d) with the hypothesis that medical intervention would both save money and improve multiyear health outcomes for these challenging patients^3,4 (see Table 1).

The study included 2,838 patients, aged 40 to 75 years, in 132 heart centers in the United Kingdom and Ireland who were randomized to placebo (n = 1,410) or atorvastatin (n = 1,428). Study entrants had no documented previous history of cardiovascular disease, normal serum LDL cholesterol concentrations, normal fasting triglyceride levels, and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. The primary end point was time to first occurrence of an acute coronary event, coronary revascularization, or stroke. Analysis of the data was by intention to treat.

The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met; the median duration of follow-up was 3.9 years. The researchers reported that atorvastatin therapy reduced the death rate by 27% (confidence interval, ?|48 to 1, P = .059) and that no excess of adverse events was noted in the atorvastatin treatment group.³

In a follow-up publication, the authors indicated that the observed 5-year time horizon of this Markov analytic model revealed that statin therapy was more cost-effective than no statin therapy.⁴ This cost-effectiveness was translated into 2005 US dollars and was linked to a quality-adjusted life-year (QUALY) metric. When the 5-year and 10-year milestones were analyzed, there was a progressive cost savings associated with the use of a statin in patients with type 2 DM of $137 to $276 per QUALY and $3,640 per QUALY, respectively.

APPLYING THE FINDINGS TO YOUR PRACTICE

Although statin therapy reduces the risk of occlusive vascular events in people with type 2 DM, there has been continued uncertainty about the effects of statins on particular long-term health outcomes and whether such effects depend on type of diabetes, lipid profile, or other factors. These CARDS data³ and the study by Ramsey and colleagues,⁴ combined with a recently published meta-analysis,⁵ confirm that statin therapy should be considered for all patients who have type 2 DM but do not have a history of cardiovascular disease or high LDL cholesterol concentrations. These new findings provide additional evidence that patients with established type 2 DM obtain benefit from statin therapy.

The choice of statin remains controversial, however. Medical and pharmacy claims from an independent managed care practice plan were reviewed for a large cohort of patients with established diabetes who were considered at high risk for cardiovascular events.⁶ These patients were treated with rosuvastatin and other statins and monitored for changes in LDL cholesterol levels. They were observed for whether LDL cholesterol targets established for diabetic patients by the National Cholesterol Education Program's Adult Treatment Panel III were achieved.⁶ The authors concluded that for patients with type 2 DM, rosuvastatin was more effective at reducing LDL cholesterol levels and attaining target levels than other statins in real-world clinical practice. However, these data did come from a retrospective analysis⁶ and are inconsistent with other findings in the peer-reviewed literature.^3,5,7-9 JAAPA

Sarah Zarbock, PA-C, department editor

REFERENCES

	1.	American Heart Association. Heart Disease and Stroke Statistics—2007 Statistical Update. Dallas, TX: American Heart Association; 2008.
	2.	Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591.
	3.	Colhoun HM, Betteridge DJ, Durrington PN, et al, on behalf of the CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet. 2004;364(9435):685-696.
	4.	Ramsey SD, Clarke LD, Roberts CS, et al. An economic evaluation of atorvastatin for primary prevention of cardiovascular events in type 2 diabetes. Pharmacoeconomics. 2008;26(4):329-339.
	5.	Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117-125.
	6.	Harley CR, Gandhi SK, Heien H, et al. Lipid levels and low-density lipoprotein cholesterol goal attainment in diabetic patients: rosuvastatin compared with other statins in usual care. Expert Opin Pharmacother. 2008;9(5):669-676.
	7.	Ali YS, Linton MF, Fazio S. Targeting cardiovascular risk in patients with diabetes: management of dyslipidemia. Curr Opin Endocrinol Diabetes Obes. 2008;15(2):142-146.
	8.	Doggrell SA. Is atorvastatin superior to other statins? Analysis of the clinical trials with atorvastatin having cardiovascular endpoints. Rev Recent Clin Trials. 2006;1(2):143-153.
	9.	Bybee KA, Lee JH, O'Keefe JH. Cumulative clinical trial data on atorvastatin for reducing cardiovascular events: the clinical impact of atorvastatin. Curr Med Res Opin. 2008;24(4):1217-1229. Epub 2008 Mar 20.