In people with 2 to 4 diabetes risk factors, high-dose atorvastatin reduced cardiovascular risk but increased new-onset diabetes compared with low-dose statins

Waters DD, Ho JE, Boekholdt SM, et al. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J Am Coll Cardiol. 2013;61:148-52.

Review question

What is the effect of statins on the incidence of diabetes in people with different risks of diabetes?

Background

Atorvastatin is a cholesterol-lowering drug of the type called statins. It prevents heart attacks and strokes. However, statins may also increase the incidence of diabetes.

How the review was done

This summary is based on an additional analysis of patient data from 2 randomized controlled trials:

• The Treating to New Targets (TNT) trial included 10,001 people 35 to 75 years of age. People were assigned to receive atorvastatin, 10 mg/day (low dose), or 80 mg/day (high dose). 50% of participants were followed for at least 4.9 years.
• The Incremental Decrease in Endpoints Through Aggressive Lipid Lowering (IDEAL) trial included 8,888 people less than 80 years of age. People were assigned to receive simvastatin, 20 to 40 mg/day, or atorvastatin, 80 mg/day. 50% of participants were followed up for at least 4.8 years.

The 2 trials were published between 2001 and 2012. Both were funded by Pfizer Inc, the company that makes atorvastatin.

Outcomes included new-onset diabetes and cardiovascular events (death from heart problems, heart attack, stroke, and resuscitated cardiac arrest).

The researchers looked at the results according to the number of diabetes risk factors people in the trials had. The 4 risk factors for developing diabetes were

• fasting blood sugar 5.6 to 6.9 mmol/L (that is, a little elevated but not high enough for the diagnosis of diabetes);
• fasting triglyceride level greater than 1.7 mmol/L;
• body mass index greater than 30 kg/m² (that is, overweight); and
• history of high blood pressure.

What the researchers found

In people with 0 or 1 diabetes risk factor

• High-dose atorvastatin did not differ from low-dose atorvastatin or simvastatin for new-onset diabetes. Overall incidence was about 3.3%.
• Compared with low-dose atorvastatin or simvastatin, high-dose atorvastatin reduced cardiovascular events by 13% (from 9.8% to 8.5%).

In people with 2 to 4 diabetes risk factors

• Compared with low-dose atorvastatin or simvastatin, high-dose atorvastatin increased the incidence of new-onset diabetes by 24% (from 12% to 14%).
• Compared with low-dose atorvastatin or simvastatin, high-dose atorvastatin reduced cardiovascular events by 16% (from 11% to 9%).

Conclusions

In people with 0 or 1 risk factor for diabetes, high-dose atorvastatin (80 mg/day) reduced cardiovascular risk compared with low-dose atorvastatin (10 mg/day) or simvastatin (20 to 40 mg/day), without increasing the risk for new-onset diabetes.

In people with 2 to 4 risk factors for diabetes, high-dose atorvastatin (80 mg/day) reduced cardiovascular risk but increased incidence of new-onset diabetes compared with low-dose atorvastatin (10 mg/day) or simvastatin (20 to 40 mg/day).

High-dose atorvastatin (80 mg/day) compared with low-dose atorvastatin (10 mg/day) or simvastatin (20 to 40 mg/day)