By Steve Borzak, MD, FACC
After 9 years, the American Heart Association and American College of Cardiology published new guidelines for the evaluation and management of elevated cholesterol guidelines. Upon publication, they immediately generated controversy, such that the New York Times opined in an editorial that Americans without established vascular disease “should probably wait until the heart organizations reassess their risk calculator.” What happened?
Noncontroversial parts of the guideline. The new guidelines emphasize that treating people with established vascular disease or diabetes—so-called high-risk individuals—is extremely well established, and that lowering LDL cholesterol with statins has been repeatedly shown to reduce death, stroke, heart attack, and the need for stenting or bypass surgery. The guidelines also acknowledge that patients without vascular disease or diabetes, but who have very high cholesterol levels, with LDL in excess of 190—so-called familial hypercholesterolemia—ought to be treated with statins.
The Four Groups. The guidelines identify four separate treatment groups. The first includes individuals with any evidence of atherosclerotic disease, for instance, having had a heart attack, stents, angioplasty, bypass surgery, having peripheral vascular or carotid disease, a stroke, and the like. The second group includes individuals without vascular disease but with an untreated LDL cholesterol of 190 or more. The third group includes diabetics without vascular disease and less than 75 years old. The last group are otherwise healthy individuals with LDL > 70 and < 190 and with a 10 year risk of vascular events > 7.5%. All four groups, in the estimation of the guidelines, justify treatment with a statin.
Gone are the targets. One surprising part of the guidelines is the emphasis on treating high-risk individuals with a potent statin drug but without a specific target. Previous guidelines emphasized an LDL below 100, or optionally below 70 for high-risk individuals. The new guidelines no longer mention a target for several reasons. First, none of the studies was conducted with a specific LDL or total cholesterol target. Rather, the large clinical trials that make up the proof of benefit all used fixed doses of statins. Thus, since the studies did not use targets, it is not rational or proven that treating to a specific target is worthwhile. For example, a high risk individual may have an untreated LDL of 95. The old guidelines would not emphasize treatment, and certainly not with a potent statin, but the new guidelines recognize that treating such an individual is important and worthwhile, and would importantly reduce the chance of future adverse events. The point is to treat the patient, and not the number.
Second, avoiding targets leads to more personalized and individualized treatment. A low risk individual with a high LDL may remain untreated, while a high risk individual should be aggressively treated, without much concern for the high-risk individual’s LDL level either before or after treatment. Since we know extremely well that potent statins reduce risk, whatever the starting LDL level, the starting and ending LDL levels do not really inform treatment in any meaningful way.
So should we check blood tests in patients on statins? The FDA previously recommended that liver enzymes should no longer be checked periodically in statin-treated patients, because the accumulated experience over decades has shown the drugs to be nontoxic to the liver, and because most liver enzyme elevations in statin patients are due to something besides the statin. The new guidelines would suggest that since a given statin dose has both a predictable effect on the LDL, and more importantly a predictable effect on reducing cardiac events, that monitoring LDL (and other lipid parameter) levels is a distraction and might only lead to adding relatively ineffective therapy (e.g., niacin, fish oil, or fenofibrate). Nonetheless, some doctors have said that blood tests reinforce positive feelings about taking the medication and verifies compliance.
The risk calculation. The most controversial part of the guideline is the recommendation to apply a new risk calculator to an otherwise healthy or low-risk individual. If the estimated risk exceeds 7.5% chance of an event in the coming 10 years, then the guideline recommends treatment. The new risk calculator replaces the Framingham score, a risk method derived from the Framingham Heart Study, which has been in use for decades. So what is so controversial? Upon publication of the guidelines, it became clear that the new calculator would recommend treating a large number of people not currently being treated. This was felt by some to be controversial. Moreover, shortly after publication, a pair of Harvard researchers applied the new risk score to several data sets and concluded that the score overestimated risk in these populations, sometimes by twofold or more. The pair suggested that calculation of risk may have changed in the several decades since the Framingham score was derived, and that more work needed to be done to insure the accuracy of the new risk calculator.
In conclusion, the familiar message reinforced by the new guidelines is that statins are safe and effective and a potent one should be used in adequate doses for at-risk individuals. This message is not new. Gone is the idea of a target LDL for treatment, which while familiar, is not evidence based. The controversy surrounding the new risk calculator and its accuracy will not be resolved soon, but should not be a distraction from the take-home message: don’t miss an opportunity to reduce your risk of vascular events with a group of the safest and most effective drugs we have.