Abandon LDL targets? Not yet


The new American College of Cardiology/American Heart Association cholesterol treatment guidelines present a substantially different approach to the treatment of patients with elevated cholesterol.

After 10 years of target-driven therapy based on important trials supporting such targets, such as PROVE IT (Pravastatin or Atorvastatin Evaluation and Infection Trial) and the TNT (Treating to New Targets) study, the new treatment guidance largely eliminates the concept of thresholds for treating LDL cholesterol as well as on-treatment therapeutic LDL targets.

Dr. Paul S. Jellinger

In most cases, the patient’s risk, not the LDL value, generates therapy. Although focusing efforts on the highest-risk patients is quite laudable, the elimination of target LDL values presents potential clinical challenges. The stratification of LDL targets for individuals at different levels of risk served as a logical and highly motivating factor for both physician and patient. The replacement of these targets with the use of the highest tolerable dose of statin, as is recommended in many cases, may be less effective in motivating patients to adhere to their regimen. The use of goals or targets has a long history of clinical usefulness in areas such as hemoglobin A1C and blood pressure control. I am concerned that just starting a statin with little or no titration may be a difficult concept for both clinicians and patients.

If patients do not fall into one of the guidelines’ three categories for aggressive statin treatment – existing cardiovascular disease, diabetes, or an LDL greater than 190 mg/dL – they are evaluated in a newly established risk calculator. It should be noted that this risk calculator has not been published, nor has it been tested for accuracy or suitability in any clinical trial.

Importantly, the risk score does not include family history of premature cardiovascular disease, triglycerides, waist circumference, or body mass index. If a patient scores with a greater than 7.5% 10-year risk for CVD events, treatment should be undertaken. This represents a significant broadening of the base for treatment, given the previous Framingham-based model that focused on a greater than 20% 10-year risk as a treatment threshold. Although there is increasing concern that too many low-risk patients will now qualify for treatment, it appears that some patients at significant risk will escape detection via this risk calculator.

For example, a 47-year-old, white, nonsmoking, nondiabetic male with a strong family history of premature coronary artery disease, total cholesterol of 230 mg/dL, HDL cholesterol of 35 mg/dL, and systolic blood pressure of 145 mm Hg while under treatment has a 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of 6.9% that does not qualify for statin treatment. Most endocrinologists would view this patient as having considerably increased risk: Low HDL is likely reciprocal to elevated triglycerides and the formation of highly atherogenic LDL particles, not to mention the family history of premature coronary disease. This patient probably has insulin resistance or metabolic syndrome, common conditions associated with accelerated coronary artery disease that escaped detection and treatment via this risk score.

Furthermore, according to the risk calculator, the patient has a 50% lifetime risk for ASCVD but we are advised not to treat. It is true that the text includes comments about considering family history of premature cardiovascular disease in individual cases, but its lack of appearance in the risk calculator could leave this very important risk factor unrecognized or overlooked. I also would like to have seen a discussion of prediabetes, a very common problem, since many clinicians set the same lipid and blood pressure goals for diabetes in their patients with prediabetes.

I applaud the AHA/ACC for their very comprehensive effort in this endeavor. There is much value in this document. The completely LDL-centric approach has likely resulted in the overtreatment of some low-risk patients with statins. Of greater concern may actually be the undertreatment of some at-risk patients using the new risk calculator. I look at this as a work in progress, with addendums and modifications to follow. The guidelines’ elimination of targets, lack of titration, and institution of aggressive therapy independent of LDL levels may be a source of confusion for patient and clinician for some time. For me, unless a clinical trial proves the principles espoused clearly valid, I am staying with my old ways, at least until the dust settles.

Dr. Jellinger is an endocrinologist in Hollywood, Fla., and a past president of the American College of Endocrinology and the American Association of Clinical Endocrinologists. He is on the speakers’ bureaus for Novo Nordisk, Boehringer Ingelheim, Janssen, Bristol Myers, and Amarin.

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