The Food and Drug Administration's announcement that the labeling of statins will now note their potential for raising a patient’s blood sugar and glycosylated hemoglobin levels is a reminder that, despite their relative safety, statin treatment poses some level of risk and hence should not be prescribed indiscriminately, experts said.
On the other hand, the risk for blood sugar elevation is modest enough that for the vast majority of patients who have significant cardiovascular disease (CVD) risk, the potential benefit from statin treatment continues to far outweigh the risk patients might face from statin-induced hyperglycemia, according to several experts interviewed for this article. Patients with cardiovascular disease risk who could remain on statins include those who have already had a cardiovascular event, the secondary prevention population, and patients who already have diabetes, considered a coronary risk equivalent because of the sizeable risk that diabetes confers for a future cardiovascular event.
"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease."
Boosted hyperglycemia that pushes a person’s fasting plasma glucose level to 126 mg/dL or above, the range diagnosed as type 2 diabetes, "is probably the most frequent quantifiable harm from statins" but is still uncommon, noted Dr. Jennifer G. Robinson, professor of medicine and epidemiology at the University of Iowa in Iowa City. She estimated that of the 10%-15% of patients who will develop type 2 diabetes over a period of several years on statin treatment, roughly 1 new case of diabetes out of every 500 incident cases will be attributable to statin treatment, based on the risk information available today.
"It's not very much. It should not change any clinician’s day to day practice in any way," said Dr. Robinson, who is also a vice-chair of the Adult Treatment Panel IV, the group assembled by the National Heart, Lung, and Blood Institute to issue new U.S. cholesterol management guidelines, expected later this year. "It just means that you don’t give a statin to everyone, not someone with a 1% risk for a cardiovascular event over the next 10 years," she said.
Primary prevention poses the most complicated issues, when physicians prescribe statins to people who have not yet had any cardiovascular event. Prescribers face the difficult question of when the risk for incident hyperglycemia triggered by a statin starts to outweigh the benefit from cardiovascular risk reduction. Further muddying the question of whom to exclude from primary prevention with statin treatment are the unknowns that shroud the effect: How do statins cause this? Which patients are most susceptible? Do different statins pose varying levels of hyperglycemia risk?
"As increasingly large populations become candidates for statin treatment, with new guidelines and new methods for CVD risk-prediction modeling, it will be very important to look at the benefit to risk ratio of treatment, including the risk for developing diabetes," said Dr. JoAnn E. Manson, professor of medicine at Harvard Medical School and chief of preventive medicine at Brigham and Women’s Hospital in Boston.
Relatively low-risk groups of patients who are increasingly prescribed statins include adolescents, young adults, and middle-aged women, she noted. "The key is the absolute risk of CVD in these groups, more than their relative risk. In a population with a low absolute risk of CVD events, we need to look very carefully to see where the crossover occurs from net benefit to net risk of treatment."
A problem for the time being is that no good way exists for identifying what factors, beyond borderline high blood glucose at baseline, help identify patients at increased risk for developing diabetes while on statin treatment. Additional research and guidance about what level of fasting plasma glucose at baseline, before a statin regimen starts, should trigger concern, and how often plasma glucose should be monitored once a patient is on a statin, will be helpful, Dr. Manson said.