Treat the Risk, Not the Cholesterol: Study Challenges Current Cholesterol Recommendations

A new study by the University of Michigan Medical School and VA Ann Arbor Health System challenges the medical thinking that the lower the cholesterol, the better.

Tailoring treatment to a patient’s overall heart attack risk, by considering all their risk factors, such as age, family history, and smoking status, was more effective, and used fewer high-dose statins, than current strategies to drive down cholesterol to a certain target, according to the U-M study.

While study authors support the use of cholesterol-lowering statins, they conclude that patients and their doctors should consider all the factors that put them at risk for heart attack and strokes.

The findings will be released online Monday ahead of print in the Annals of Internal Medicine.

“We’ve been worrying too much about people’s cholesterol level and not enough about their overall risk of heart disease,” says Rodney A. Hayward, M.D., director of the Veterans Affairs Center for Health Services Research and Development and a professor of internal medicine at the University of Michigan Medical School.

The National Cholesterol Education Program recommends harmful LDL cholesterol levels should be less than 130 for most people. High risk patients should be pushed even lower -- to less than 70.

The U-M study took a different approach, called tailored treatment, which uses a person’s risk factors and mathematical models to calculate the expected benefit of treatment, by considering:

• A person’s risk of a heart attack or stroke without treatment;
• How much a statin decreases the risk; and
• Potential harms from the treatment

“These are the three factors that determine the net benefit of a treatment. Our fixation on just one factor, LDL cholesterol, is leading us to often treat the wrong people,” Hayward says.

In the recent study, U-M physicians who worked with Yale University School of Medicine used data from statin trials that included Americans ages 30-75 with no history of heart attack.

Study authors evaluated the benefit of five years of treatment that was tailored, on coronary artery disease risk factors such as age, family history, diabetes, high blood pressure, smoking status, and recently CRP, C-reactive protein.

The tailored approach was more efficient (more benefit per person treated) and prevented substantially more heart attacks, strokes and cardiovascular deaths than the currently recommended treat-to-target approaches.

The tailored strategy treated fewer individuals with high-dose statins and saved 500,000 more quality-adjusted life years.

“The bottom line message – knowing your overall heart attack risk is more important than knowing your cholesterol level,” Hayward says. “If your overall risk is elevated, you should probably be on a statin regardless of what your cholesterol is and if your risk is very high, should probably be on a high dose of statin,” the U-M physician says.

“However, if your LDL cholesterol is high, but your overall cardiac risk is low, taking a statin does not make sense for you,” Hayward says. “If your cholesterol is your only risk factor and you’re younger, you should work on diet and exercise.”

Research has increasingly emerged questioning the value of cholesterol targets and which of statins mechanisms is most important to preventing cardiac events. Cholesterol-lowering drugs work by blocking a key enzyme linked with LDL cholesterol production, but they initiate other changes in the body.

“Statins also affect inflammation on the inside of our blood vessels which is often what causes heart attacks and strokes – it’s not just a matter of cholesterol alone,” he says.

Additional authors: Harlan M. Krumholz, M.D., Yale University School of Medicine, and Donna M. Zulman, M.D., Justin W. Timbie, Ph.D., and Sandeep Vijan, M.D, all of the VA Center for Health Services Research and Development, VA Ann Arbor Health Care System.

Funding: VA Health Services Research and Development Service’s Quality Enhancement Research Initiative and the Measurement Core of the Michigan Diabetes Research & Training Center of the National Institutes of Health.

Abstract

BACKGROUND: Although treating to lipid targets ("treat to target") is widely recommended for coronary artery disease (CAD) prevention, some have advocated administering fixed doses of statins based on a person's estimated net benefit ("tailored treatment"). OBJECTIVE: To examine how a tailored treatment approach to statin therapy compares with a treat-to-target approach. DESIGN: Simulated model of population-level effects of treat-to-target and tailored treatment approaches to statin therapy. DATA SOURCES: Statin trials from 1994 to 2009 and nationally representative CAD risk factor data. TARGET POPULATION: U.S. persons aged 30 to 75 years with no history of myocardial infarction. TIME HORIZON: Lifetime effects of 5 years of treatment. PERSPECTIVE: Societal and patient. INTERVENTION: Tailored treatment based on a person's 5-year CAD risk (simvastatin, 40 mg, for 5% to 15% CAD risk and atorvastatin, 40 mg, for CAD risk >15%) versus treat-to-target approaches that escalate statin dose per National Cholesterol Education Program [NCEP] III guidelines (including an intensive approach that advances treatment whenever intensification is optional by NCEP III criteria). OUTCOME MEASURES: Quality-adjusted life-years (QALYs). RESULTS OF BASE-CASE ANALYSIS: Compared with the standard NCEP III approach, the intensive NCEP III approach treated 15 million more persons and saved 570,000 more QALYs over 5 years. The tailored strategy treated a similar number of persons, as did the intensive NCEP III approach, but saved 500,000 more QALYs and treated fewer persons with high-dose statins. RESULTS OF SENSITIVITY ANALYSIS: No circumstances were found in which a treat-to-target approach was preferable to tailored treatment. LIMITATION: Model assumptions were based on available clinical data, which included few persons 75 years or older. CONCLUSION: A tailored treatment strategy prevents more CAD events while treating fewer persons with high-dose statins than low-density lipoprotein cholesterol-based target approaches. Results were robust, even with assumptions favoring a treat-to-target approach. PRIMARY FUNDING SOURCE: Department of Veteran Affairs Health Services Research & Development Service's Quality Enhancement Research Initiative.

Source

Hayward RA, Krumholz HM, Zulman DM, Timbie JW, Vijan S. Optimizing statin treatment for primary prevention of coronary artery disease. Ann Intern Med. 2010 Jan 19;152(2):69-77. PMID: 20083825

University of Michigan Health System, Released: 1/18/2010

Key concepts: LDL, cholesterol, cardiovascular risk factors