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Changes to the statin label: What they really mean


The FDA has made changes to the safety label for statins, the cholesterol-lowering drugs that over 20 million Americans take in hopes of reducing their chances of having a heart attack or stroke. When the changes were announced in February 2012, it reignited a smoldering debate about the benefits and risks of statins.

If you want our bottom line, here it is: the vast majority of people taking statins should continue to take them, but some additional attention to blood sugar levels is warranted. And, as with any medication, if you’re taking a statin and experience side effects, you shouldn’t hesitate to contact your doctor.

Interested in more details? Read on.

Increases in blood sugar levels

The safety information for statins now says that increases in HbA1C and fasting serum glucose levels have been reported. HbA1C is a blood test that reflects average blood sugar levels; serum glucose is just another way of saying blood sugar.

The warning doesn’t mention diabetes, but that is, of course, the concern if blood sugar stays high. An important meta-analysis published in 2010 in The Lancet concluded that taking a statin increased the chance of developing diabetes by 9%. More proof came last year with the publication of a smaller meta-analysis of higher doses of statins taken with more ambitious LDL-cholesterol–lowering goals in mind. Not surprisingly, “intensive” statin therapy was associated with a higher (12%) risk of developing diabetes.

Researchers analyzing data from the Women’s Health Initiative (WHI), a large, government-sponsored study of postmenopausal women, reported earlier this year that statin use was associated with a 48% increase in new-onset diabetes. But because this aspect of the WHI trial wasn’t randomized, there are statistical and methodological reasons that may explain the results and the high incidence of diabetes. Still, the WHI results do fit into the broader picture: a certain, but probably small, percentage of people who go on statin therapy are prone to developing diabetes.

But it can’t be left there, with a risk of statins artificially divorced from their considerable benefits. An important meta-analysis published two years ago concluded that statins reduce the risk of heart attack, stroke, and major cardiovascular procedures by about 20% for each 40 mg/dL decrease in LDL cholesterol they achieve. The size of the risk reduction varies some with age, health, and gender.

Set against the diabetes risk—putting aside the WHI finding—the benefits of statins win out.

Risk reduction presented in relative terms with percentages can be misleading. Another—and probably better—way to look at the risk-benefit balancing act is to compare the number of people affected by the side effects to the absolute number of people who benefit from statins. The calculations done by the researchers who conducted the 2010 meta-analysis are a good example. They computed that over a four-year period there would be one additional case of diabetes for every 255 people taking a statin, but also 5.4 fewer heart attacks and deaths from heart-related conditions.

Ideally, we’d have tests that would pinpoint exactly who is harmed by, and who benefits from, statins. But even without that kind of specificity, it is clear that the diabetes risk isn’t distributed evenly. Older people are more vulnerable than younger people. And some experts say the risk is largely confined to people who already tend to have high blood sugar levels, with statins just tipping the balance.

No one knows exactly why statins sometimes increase blood sugar levels. They may have some effect on insulin and its activity. Interestingly, other important cardiovascular drugs—thiazide diuretics, beta blockers, niacin—also increase the risk for developing diabetes.

Possible cognitive impairment

Cognitive impairment sounds scary, but the FDA warning is actually pretty mild. It says there have been postmarketing reports (FDA-speak for reports after a drug has been approved) of cognitive impairment; the problems were generally not serious; and that they go away once people stop taking a statin. (The exact wording varies some from product to product.) The warning is based on data from the agency’s Adverse Event Reporting System (AERS), which collects reports from doctors and the public after a drug is on the market. AERS data are important and can identify problems with drugs that weren’t apparent in studies used to gain FDA approval. But unless there’s a strong pattern, it’s just a collection of anecdotes, and that may be the case here. When researchers have looked for associations between statins and cognitive problems in randomized trials, they haven’t, for the most part, found any.

Routine liver tests aren’t needed

The new label—which isn’t really a label but a long, technical document—says people should get liver enzyme tests before they start taking a statin and if after taking one, they have symptoms, such as jaundice, that are suggestive of liver disease. But routine testing of liver enzymes, which is often done at the same time as a cholesterol check, is no longer recommended for two reasons. Liver damage from statins is extremely rare (two or fewer cases per 1 million patient-years, according to the AERS database), and routine testing doesn’t help spot those rare (and inexplicable) cases. In fact, routine liver enzyme tests are probably counterproductive because people may stop taking a statin after the results show a spike in certain liver enzymes (typically aminotransferase) when that increase is almost certainly meaningless and has nothing to do with the statin.

Posted by: Dr.Health

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