New Cholesterol Guidelines Overlook Many Patients

Cholesterol-treatment guidelines released by the American College of Cardiology and American Heart Association in November 2013 were based primarily on randomized clinical trial (RCT) evidence supporting a reduction in adverse cardiovascular outcomes with treatment, primarily statins. The guideline recommends statin therapy for patients:

• With clinical cardiovascular disease (CVD)
• With an LDL-C level of 190 mg/dL or higher
• Age 40-75 with diabetes
• Age 40-75 without diabetes, but with an LDL-C level of 70-189 mg/dL and a 10-year cardiovascular risk of 7.5 percent or more, as determined by a new risk calculator.

The recommendations eliminate target LDL-C goals and simply recommending intensive statin therapy to lower LDL-C by 50 percent or more in high-risk patients and 30-50 percent in medium-risk patients in the above categories.

Major limitations noted

According to Cleveland Clinic cardiologist Michael Rocco, MD, emphasizing the use of statins in high-risk populations is well supported by clinical evidence. However, these guidelines do not offer clear guidance on populations falling outside these boundaries, for whom clinical trials were insufficient to draw conclusions.

“This may deny therapy to other at-risk populations and those with substantial residual risk, even while on statin therapy,” he says.

Additionally, he does not think that eliminating treatment goals is a good idea.

“We see potential benefits for maintaining LDL-C target goals, including patient compliance and motivation. They also provide physicians with a means to ensure that the desired effect is achieved,” he says.

Ignoring pathophysiology

Moreover, the new recommendations ignore the pathophysiology of coronary artery disease, consistent evidence from observational and clinical trial subset analyses and evidence of residual risk in patients on moderate and high-intensity statin therapy, particularly those with diabetes and metabolic syndrome.

“These recommendations fail to consider the potential benefit of treating to lower LDL-C or non-HDL-C goals in high-risk patients already on maximal tolerated statin doses and curtail consideration of combination drug therapy,” he says.

An additional risk is the potential for undertreatment and overtreatment. “Is it appropriate to not treat a 38-year-old male with an LDL-C of 179 mg/dL and a strong family history of premature cardiovascular (CVD) events?” he queries. “Conversely, does titrating a 65-year-old female with diabetes and an LDL-C of 53 mg/dL on 10 mg of atorvastatin titrating to high-intensity doses potentially expose her to excessive risk of side effects?”

Biggest disappointment: risk calculator

The authors developed a new risk calculator for targeting therapy based on the 10-year risk of CVD events in individuals without CVD or diabetes. Because it has never been tested prospectively, its value has not been confirmed. When Boston cardiologists applied the calculator to patients in completed recent clinical trials, it overestimated their risk by 75 to 150 percent.

“It is difficult to implement a guideline that strives to use only randomized controlled trials for recommendations, but used an untested risk calculator to guide therapy,” said Dr. Rocco and his colleagues in an article on the guidelines in the January 2014 Cleveland Clinic Journal of Medicine.

According to the risk calculator, a 62-year-old black male, nonsmoker, LDL-C 84 mg/dL, HDL-C 70 mg/dL, total-C 170 mg/dL, without diabetes or hypertension, has a 10-year risk of 7.9 percent and should be placed on moderate-intensity statin therapy.

The calculator fails to consider family history and other risk factors, such as triglyceride levels or hsCRP, which may potentially aid in risk assessment and treatment decisions.

“We could be delaying treatment for people who could benefit,” says Dr. Rocco.

What the guidelines got right

The guidelines received a “thumbs up” for classifying patients with peripheral and cerebrovascular disease as high risk and recommending aggressive treatment of patients with diabetes.

They also emphasize the use of statins as first-line therapy and recommend using the highest-tolerated doses. Dr. Rocco agrees with this thinking. “Moving from lower-to- higher potency statin therapy has been associated with incremental reduction in adverse CVD events in high-risk individuals. If you are going to treat, you should optimize the dose of the most effective therapy to get the desired results,” he says.

Individualized therapy still valid

The bottom line is that guidelines should be viewed as a panel’s expert opinion, rather than rules.

“They are a starting point,” says Dr. Rocco. “Clinical trials do not always provide the best guidance for an individual patient. You have to look at the individual’s risk and make treatment decisions on a case-by-case basis. We recommend a hybrid approach maintaining LDL-C goals, with emphasis on risk assessment and high-intensity statin therapy in high-risk populations.”