High-Dose Atorvastatin Associated with Worsening Glycemic Control

Atorvastatin was associated with a statistically significant increased risk of developing an HbA1c greater than 6 — both in non-diabetics and in diabetics. A review of results from a major trial that compared the effectiveness of two statin drugs shows that loss of glycemic control occurs more often with high-dose atorvastatin than with pravastatin.

"Clearly this represents a sign to physicians that if they have patients on high-dose atorvastatin, they need to monitor their patients’ glucose status," said presenter Marc Sabatine, MD, associate physician, Brigham & Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, Massachusetts.

The Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT TIMI 22) study enrolled more than 4,000 patients with acute coronary syndromes. It showed that fewer major acute cardiac events occurred with atorvastatin than with pravastatin, Dr. Sabatine said.

In his oral presentation, he reported that an increase of 0.5% in hemoglobin A1c (HbA1c), a marker of glycemic control, occurred in 28% of subjects taking pravastatin 40 mg, compared with 44% of patients on atorvastatin 80 mg, who showed a 0.5% increase.

"This is a result we didn’t expect," Dr. Sabatine said. "Intense lipid lowering may be a problem with glycemic control."

Among the 3382 patients without pre-existing diabetes, HbA1c increased by 0.12% in patients treated with pravastatin and by 0.30% in patients treated with atorvastatin, an increase that reached statistitical significance at the P <.0001 level, he said.

"Atorvastatin was associated with a statistically significant increased risk of developing an HbA1c greater than 6 — both in non-diabetics and in diabetics," Dr. Sabatine said. However, he noted, "one of the limitations of this study is that we found the relationship in an ad hoc analysis of the data." For that reason, he said, the results would need to be further validated.

The PROVE-IT trial was funded by Bristol-Myers Squibb, marketer of pravastatin.
American Heart Association Scientific Sessions 2004. November 10^th
[Presentation title: "High-Dose Atorvastatin Associated with Worse Glycemic Control: A PROVE-IT TIMI 22 Substudy." Abstract 3848]

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