Preventing Coronary Disease in Diabetics

Summarized by Robert W. Griffith, MD
July 2, 2004

Introduction

Type 2 diabetes commonly results in vascular problems; these may be microvascular (retinopathy, nephropathy, and neuropathy) or macrovascular (coronary artery disease, cerebrovascular disease, and peripheral vascular disease). To avoid such complications, it's necessary to manage both the hyperglycemia and cardiovascular risk factors. The latter include dyslipidemia, particularly hypercholesterolemia.

The American College of Physicians (ACP) has published guidelines to help internists and primary care physicians effectively manage dyslipidemia in type 2 diabetics, and they are summarized here.

Background to the recommendations

In formulating the guidelines, the ACP committee addressed the following questions:

1. What are the benefits of tight lipid control for the primary and secondary prevention of vascular complications in type 2 diabetes?
2. What should the target level be for low-density lipoprotein (LDL) cholesterol in such patients?
3. Are some lipid-lowering agents more effective than others in this respect?

The data the committee used was taken from a review (in the same journal) of 6 primary prevention and 8 secondary prevention randomized controlled studies.¹ The endpoints used to supply evidence for the guidelines were all-cause mortality, cardiovascular mortality, and a cardiovascular event (i.e. an MI, stroke, and cardiac death). The analyses were designed to lead to recommendations for secondary and primary prevention in order to achieve meaningful improvement in the likelihood of cardiovascular events for type 2 diabetics.

For the secondary prevention studies, meta-analysis revealed a decreased absolute risk by 7%; 14 patients would need to be treated for 5 years to prevent one cardiovascular event. For primary prevention, statin therapy reduced the absolute risk by 3%; 35 patients would need to be treated for 5 years to prevent one cardiac event.

The recommendations

These are the committee's recommendations, quoted word-for-word:

1. Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type 2 diabetes.
2. Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type 2 diabetes and other cardiovascular risk factors.
3. Once lipid-lowering therapy is initiated, patients with type 2 diabetes should be taking at least moderate doses of a statin.
4. For those patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

There are some points that need further explanation. Relative risk reduction was similar in both secondary and primary prevention. Absolute risk reduction was almost double, however, in secondary prevention, as patients with known coronary artery disease clearly had a greater absolute risk.

Statins should be the drug-of-choice for secondary prevention, unless the patient has low levels of both HDL and LDL cholesterol; in this case, gemfibrazol is effective in reducing absolute risk of cardiovascular events. The significant risk factors listed to help define secondary prevention were: age above 55, hypertension, smoking, left ventricular hypertrophy, previous cerebrovascular disease, and peripheral arterial disease.

In the primary prevention studies in type 2 diabetics, the initial LDL cholesterol levels were not relevant to the outcome, even when they were below 100 mg/dL (2.6 mmol/L). Moreover, there was little evidence pointing to the benefits of treating to a specific target LDL or total cholesterol level.

Statin dosages

Although there was insufficient evidence to make specific recommendations regarding dosing for primary prevention, the committee says the following would be most reasonable: atorvastatin 20 mg/day, lovastatin 40 mg/day, pravastatin 40 mg/day, or simvastatin 40 mg/day.

For secondary prevention, the clinical trials employed the following doses: fluvastatin 80 mg/day, lovastatin 40 to 80 mg/day, pravastatin 40 mg/day, and simvastatin 20 to 40 mg/day. Gemfibrazol was given at a dose of 1200 mg/day, where indicated.

At these dose levels, rates of elevated liver function tests and muscle enzyme levels were the same in the treatment and the placebo groups; hence the final recommendation, about the absence of need for routine monitoring. Rates of discontinuation of medication were similar in both treatment and placebo groups.

Comment

Overall, lipid-lowering medication leads to a 22% to 24% reduction in major cardiovascular events in patients with type 2 diabetes. This applies equally to people with diabetes whose baseline LDL cholesterol is not elevated. Doses of statins should be moderate, and are likely to be extremely safe in the vast majority of patients.

Source

• Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. V. Snow, MD. Aronson, R. Hornbake,  et al., Ann Intern Med, 2004, vol. 140, pp. 644--649

Footnotes
1. Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians. S. Vijan, RA. Hayward, Ann Int Med, 2004, vol. 140, pp. 650--658

Related Links
Managing Cardiovascular Disease in Type 2 Diabetes
Exercise Helps Control Diabetic Vascular Disease
Multifaceted Approach to Diabetes Management
ACE Inhibitor Beneficial in Diabetics at Risk

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