Statins and Diabetes Mellitus: part 2

31 Mar

HDL also seems to be more quickly hydrolyzed in patients with insulin resistance, leading to lower HDL levels. Statins can reduce LDL levels by 18% to 55% and triglycerides by 7% to 30%; they can also increase HDL levels by 5% to 15%.

Although few studies have been directed solely toward statin use in the diabetic population, many studies have included a sufficient number of diabetic patients to extrapolate relevant information. One of the largest diabetic populations was involved in the Heart Protection Study (HPS). Baseline requirements included a total cholesterol level of at least 135 mg/dl, which implies possible inclusion of diabetic patients with and without dyslipidemia prior to intervention.

The study found that diabetic patients taking daily (Zocor canadian, Merck) had a highly significant reduction in the incidence of a first nonfatal MI or coronary death (95°% CI 15-38; P < .0001) compared with placebo. The incidence of stroke was similarly reduced (95% CI 6-39; P = .01). Both percentages of reductions were similar to those of high-risk patients who were enrolled in the study who did not have diabetes. The study concluded that in initiating statin therapy as the standard of care for diabetic patients, physicians should evaluate a patient’s overall risk of having a major coronary event.

The Collaborative Atorvastatin Diabetes Study (CARDS) included only patients with type-2; these patients were required to have a diagnosis of type-2 diabetes, at least one other risk factor for coronary heart disease, and normal LDL concentrations. The study found a reduction in MI by 36%, stroke by 48%, and the need for revascularization by 31%. The trial was terminated two years earlier than expected because of significant positive outcomes in the treatment group.

Now that these two large trials, along with several other trials, have shown data to support the use of statins in diabetic patients with and without dyslipidemia, the question is: Are we adequately managing our diabetic patients?

A study in 2004 claimed that patients are not being optimally treated. The HPS and CARDS announced their findings in 2003, but not much has changed in the past three years. We have reached a point where it is important for us to re-examine our standard of care for diabetic patients. Currently, the recommendations state that a goal of below 100 mg/dl for LDL is beneficial in preventing coronary events and that a goal of less than 70 mg/dl should be considered in diabetic patients with additional risk factors. Controversy still remains as to whether the LDL goal for all diabetic patients should be below 70 mg/dl.

The American Diabetes Association currently recommends the use of statins in all diabetic patients over 40 years of age with a total cholesterol level of more than 135 mg/dl, regardless of baseline LDL levels or the presence of coronary heart disease.

There is evidence supporting the routine use of simva-statin or atorvastatin (Lipitor, Pfizer) in these patients. However, high-dose simvastatin raises some concerns about adverse events. Physicians must exercise caution and weigh the risks and benefits when considering statins, especially high doses of simvastatin, as the standard of care in diabetic patients.

An article by Dr. Steve Nissen highlights the safety concerns that were addressed in the famous A to Z [Aggrastat to Zocor] trial. Published in 2004, this trial compared the safety and efficacy of high-dose simvastatin versus low-dose therapy. The study concluded that there was no difference or acute coronary syndrome; however, it noted an alarming increased risk of myopathy at doses of simvastatin 20 mg.

Statins are known to reduce the cardiovascular risks in patients with dyslipidemia; now they are predicted to have just as much benefit in patients with type-2 diabetes mellitus. The risks and the benefits of statins should always be evaluated on a case-by-case basis. However, good data suggest that statins should be routinely used in our diabetic population to decrease morbidity and mortality because of their ability to reduce LDL levels by 30% to 40% regardless of baseline values. The next big step vis-a-vis clinical guidelines is to decide whether lower LDL is, in fact, better for all diabetic patients.