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Question: Should we use statins as first line to reduce cardiovascular mortality in all diabetes patients?
Answer: Yes, for most patients, but not for all. People with type 2 diabetes have two to four times the risk for cardiovascular disease (CVD) of those without diabetes. The increased risk in those with diabetes without known CVD is equivalent to that of people without diabetes but with preexisting cardiovascular events.1 All three of the commonly used lipid parameters—LDL, HDL, and triglycerides—play a role in this increased risk.2
Pharmacological intervention is similar to intervention used to treat those without diabetes—blood pressure control and lipid lowering have been shown in many studies to reduce both cardiovascular and cerebrovascular events. Most of the data available to support statin use in preventing myocardial infarction (MI) are from subgroup analyses of secondary prevention studies; for example, the Scandinavian Simvastatin Survival Study found a 50% relative risk reduction for diabetes subjects placed on 20 mg/day of simvastatin.3 The Heart Protection Study (HPS) found an 11% risk reduction in a similar population treated with 40 mg simvastatin.4
HPS also included data on primary prevention in 3,982 patients with diabetes and LDL cholesterol >135 mg/dl. Treatment with 40 mg simvastatin resulted in a 26% relative risk reduction for coronary heart disease events, with an absolute risk reduction of 5%.
Meta-analyses of both primary and secondary prevention studies found a 22–24% relative risk reduction with lipid lowering therapy.5 Although the relative risk reduction is similar for primary and secondary prevention, the absolute risk is 7% greater for the secondary prevention group.
So, statin therapy clearly lowers cardiovascular risk in type 2 diabetes in the presence of other risk factors, particularly a history of cardiovascular events. What about type 2 diabetes in the absence of other risk factors? The CARDS trial showed similar results as HPS in patients with type 2 diabetes without risk, demonstrating a 36% risk reduction for acute coronary events in those randomized to 10 mg atorvastatin as compared with placebo. The third report from the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) suggests that diabetes should be considered the equivalent of pre-existing CVD and supports a more aggressive approach in these patients for two reasons. First, the presence of type 2 diabetes confers a significantly increased risk of MI within the next 10 years. Second, people with diabetes have poorer outcomes after MI or stroke.3
To summarize, the increased risk of MI in people with diabetes has led to
the American Diabetes Association recommendation that people > 40 with type
2 diabetes should be treated with a statin in doses high enough to lower LDL
cholesterol levels by 30–40% regardless of baseline LDL
cholesterol. For those < 40, lipid lowering therapy is advised for
people with other risk factors, including hypertension, family history,
abdominal obesity, and high triglycerides. Type 2 diabetes is rarely present
without most or all of these other risk factors; thus, statins should be
considered in almost all people with type 2 diabetes. 
Footnotes
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Note of Disclosure: Lorber served on a speaker panel for Merck & Co. and Novartis and received research support from Merck, Novartis, and Mann Kind Corp.
References
2. Turner RC, Millns H, Neil HA, et al.: Risk factors for coronary
artery disease in non-insulin dependent diabetes mellitus: United Kingdom
Prospective Diabetes Study (UKPDS: 23). BMJ 316: 823–828, 1998.
3. NCEP 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 on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
Panel III). JAMA 285:2486–2497, 2001.
4. Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial. Lancet 361:2005–2016, 2003.[Medline]
5. Vijan S, Hayward RA: Pharmacologic lipid-lowering therapy in type 2
diabetes mellitus: Background paper for the American College of Physicians.
Ann Intern Med 140:650–658, 2004.
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