NCEP update promotes more aggressive statin therapy for some patients

Goal still may not be reachable for some, panel pharmacist says

The National Cholesterol Education Program’s (NCEP) clinical practice guidelines on cholesterol management have been updated to set even lower treatment goals for low-density lipoprotein (LDL) cholesterol for patients at high and moderately high risk for a heart attack. The guidelines, for example, offer a new therapeutic option for very high-risk patients to achieve levels of less than 70 mg/dL.

The update is based on a review of five major clinical trials of statin therapy conducted since the 2001 release of the NCEP’s cholesterol guidelines known as the Adult Treatment Panel (ATP) III Report. The update, published in the July 13 issue of Circulation: Journal of the American Heart Association, is endorsed by the National Heart, Lung, and Blood Institute (NHLBI); the American College of Cardiology; and the American Heart Association.

The update is an advance in the treatment options, says James M. McKenney, PharmD, emeritus professor at the School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University and president and CEO of National Clinical Research, both in Richmond. McKenney has been a member of the coordinating and executive committees of NCEP since its inception in 1985. He was appointed to the ATP II and III to develop guidelines for the evaluation and treatment of hyperlipidemia.

Recommending more intensive therapy was on the minds of the developers of the ATP III report, McKenney says. "We were trying to be as evidence-based with the recommendations as we could, so we couldn’t advise clinicians in the country to manage patients, even if they had risk, with low levels of LDL. The Heart Protection Study [one of the five clinical trials] solved that one for us. I think it’s a good example of where these guidelines have reached a little bit further and added a few more patients to the treatment list. They can justify that based on now-clear evidence that these patients benefit from that treatment."

Major recommendations of the report

Here are some of the major recommendations of the report, according to the NHLBI:

High and very high risk. For high-risk patients, the overall goal remains an LDL level of less than 100 mg/dL. But for people at very high risk, the update offers a new therapeutic option of treating until levels are below 70 mg/dL. For very high-risk patients whose LDL levels are already below 100 mg/dL, there also is an option to use drug therapy to reach the less than 70 mg/dL goal.

For the overall category of high-risk patients, the update lowers the threshold for drug therapy to an LDL of 100 mg/dL or higher and recommends drug therapy for those high-risk patients whose LDL is 100-129 mg/dL. ATP III had set the threshold for drug therapy for high-risk patients at an LDL of 130 mg/dL or higher, and made drug treatment optional for patients with an LDL level of 100-129 mg/dL.

Moderately high risk. For these patients, the goal remains an LDL of less than 130 mg/dL, but the update provides a therapeutic option to set a lower LDL goal of less than 100 mg/dL and to use drug therapy at LDL levels of 100-129 mg/dL to reach this lower goal.

For high-risk or moderately high-risk patients, the report advises that the intensity of LDL-lowering drug therapy be sufficient to achieve at least a 30%-40% reduction in LDL levels. This can be accomplished by taking statins or by combining lower doses of statins with other drugs (e.g., bile acid resins, nicotinic acid, or ezetimibe) or with food products containing plant stanol/sterols.

Lower/moderate risk. The update did not revise recommendations for lower-risk people: those with moderate risk (two or more risk factors plus a less than 10% risk of a heart attack in 10 years) or those with 0 or 1 risk factor. According to the report, the absolute benefits for people at the lower levels of risk are less clear cut, and the recent clinical trials do not suggest a modification of treatment goals and cut points.

Some health care providers have criticized the use of the term "therapeutic option," saying it is too vague. The term is used because the treatment is driven by clinical judgment, McKenney says. "What is a very high risk as opposed to just a high-risk patient? It’s in the eyes of the beholder. That’s where we think clinical judgment needs to be played.

"It needs to be a decision made by the clinician who is trying to put together the risk level of that patient and the appropriate goal given that patient’s risk level," he says. "My answers may be different from the next person."

Millions more should be treated

The change in the update may seem small, but it affects the treatment of millions of people. "In the original estimate that ATP III published a couple of years ago, we assumed that none of the high-risk patients with LDLs less than 100 would be treated," McKenney says. "We assumed that only half of those with untreated levels between 100 and 129 — borderline range — would be treated. Those are the only new pockets of patients who have been brought in."

Those new pockets of people, however, add 8 million patients to the potential drug treatment category, he says. "You go from 36 million to about 44 million. It shows how what seems to be a fairly small change actually does produce a lot of people who are potential candidates for drug therapy."

Bringing these patients to the new recommended LDL levels may be enormously difficult, McKenney adds. "No one thinks this is going to be easy. Nor is it going to be possible in all patients."

For example, a physician treating a patient with familial hypercholesterolemia, who has the average LDL at the beginning of treatment of 200 or 250, may not be able to reduce the level to 70. "I think it may be humanly impossible to add enough drugs on to get there. After you get to about four drugs, I can’t think of anything else to add.

"We understand this is not going to be possible for everyone, but the message is there. If patients are very high risk, they deserve the most aggressive treatment that you can give them because their chance of having a [heart attack] in the next 10 years is more than 25%. They will benefit if you can come close to the 70, even it you don’t get to it."

Health care providers must do the best they can, McKenney says. "You try to bring the patient down as close to the range that you can and know that you are helping that patient with every percent lowering that you can achieve."

Hospital pharmacists need to develop programs so that patients can be discharged on the most appropriate and the most aggressive treatment, he concludes. "We all know that patients who leave the hospital after their revascularization procedure or after their stroke or even after their hospitalization for diabetes with lipid-lowering therapy are much more likely to stay on that treatment and much more likely to get to goal."