Investigators Provide Rationale for New LDL Guidelines
Updated guidelines for cholesterol testing and management (Adult Treatment Panel (ATP) IV) from the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults are due to be published in 2012. These influential guidelines are organized and funded by the National Heart, Lung, and Blood Institute (NHLBI) and carry the sanction of the federal government. A primary focus of the previous version of the guidelines was to treat patients to target low-density lipoprotein (LDL) cholesterol levels, with the primary goals of therapy and the cut-points for initiating treatment stated in terms of LDL. However, the authors believe this reasoning diverges from clinical evidence. This open letter to the ATP Committee provides the rationale for why the new guidelines should abandon the treat-to-target paradigm.
Authors present the following primary reasons that justify a major change in the next generation of ATP:
- There is no scientific basis to support treating to LDL targets.
- No major randomized clinical trial has tested the benefits of treating patients according to LDL targets.
- Trials do not demonstrate that all drugs that reduce lipid levels reduce patient risk for cardiovascular events.
- Trial evidence does indicate that the use of statins – and not treatment to target – can reduce risk; for example, standard doses of the first generation of statins dramatically reduce cardiovascular events and mortality.
- The safety of treating to LDL targets has never been proven.
- LDL target-based guidelines can lead to recommendations to treat patients with a low risk of cardiovascular outcomes, thus minor risks could outweigh benefits.
- Although statins can have appreciable side effects, along with potentially serious drug-drug interactions, they have been shown to be relatively safe over a 5- to 7-year treatment period. But longer-term safety is not yet known.
- LDL targets are commonly used to promote the use of newer lipid-lowering treatments, often in combination with a statin. However, evidence that they reduce cardiovascular events is lacking, as are adequate safety data.
- Tailored treatment is a simpler, safer, more effective, and more evidence-based approach.
- The model for a simple tailored treatment approach, in which statin treatment intensity is based on a person’s overall 5- to 10-year cardiovascular risk regardless of LDL level, was estimated to save about 100,000 more quality-adjusted life years, while having fewer people on high doses of statins than a treat-to-target approach.
This perspective is synergistic with recent activities in VA, in which a multidisciplinary group of leaders from Diabetes, Cardiology, and Performance Measures provided input that led to the suspension of VA’s Performance Measure that was strictly focused on achievement of lipid targets (LDL< 100). They are now working to substitute a performance measure that emphasizes the prescription of statin medications. In addition, VA is helping to inform the CDC/HHS Million Hearts Initiative with regard to emphasizing cholesterol management (with statin medications) rather than treat-to-target/cholesterol control.
This work was partly supported by VA/HSR&D’s Diabetes Quality Enhancement Research Initiative (QUERI). Dr. Hayward is part of HSR&D’s Center for Clinical Management Research, Ann Arbor. Dr. Krumholz, a researcher at Yale School of Medicine, is on the Executive Committee of the Ischemic Heart Disease (IHD) QUERI.
Hayward R and Krumholz H. Three Reasons to Abandon Low-Density Lipoprotein Targets: An Open Letter to the Adult Treatment Panel IV of the National Institutes of Health. Editorial. Circulation: Cardiovascular Quality and Outcomes January 2012:5(1):2-5.