Paradigm Change: New Guidelines on Managing Cholesterol

Boston—New guidelines on managing cholesterol in adults offer recommendations on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) risk that differs substantially from previous guidelines.

Published in 2013 jointly by the American College of Cardiology and American Heart Association, the new guidelines make no recommendations for or against specific low-density lipoprotein (LDL) cholesterol or non–high-density lipoprotein cholesterol targets for the primary or secondary prevention of ASCVD risk [Circulation. 2013;129(25 suppl 2):S1-S45].

“This is a large paradigm change for clinicians,” said Joseph Saseen, PharmD, professor, vice chair, department of clinical pharmacy, professor, department of family medicine, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado. “The long-standing recommendation to target a specific LDL cholesterol goal and titrate therapy to achieve that goal number is replaced with fixed-intensity statin-based therapy as the primary treatment recommendation for most patients.” Dr. Saseen discussed the new guidelines during a session at the AMCP meeting.

Dr. Saseen highlighted that the new guidelines recommend the benefit of statin therapy for 4 specific patient groups: (1) patients with clinical ASCVD; (2) patients with LDL cholesterol >190 mg/dL; (3) patients 40 to 75 years of age with type 1 or 2 diabetes; and (4) patients 40 to 75 years of age with a >7.5% estimated 10-year ASCVD risk.

He discussed some of the evidence used as the basis for the recommendations for statin therapy in these patient groups, emphasizing the level and strength of the evidence for each group. Recommendations were classified as class 1, benefits clearly outweigh risks; class 2a, benefits outweigh risks; and class 2b, benefits are greater or equal to risks; and then given a level of recommendation based on the type of evidence. Level A was based on multiple, randomized, controlled trials or meta-analyses; level B was based on a single, randomized, clinical trial or noncontrolled studies; and level C was based on consensus opinion.

For example, the recommendation for statin therapy for patients with clinical ASCVD was based on the highest level and strength of evidence—class 1 recommendation with level A evidence. For this group of patients, the guideline specifies “high-intensity statin therapy should be initiated or continued as first-line therapy in men and women <75 years of age who have clinical ASCVD, unless contraindicated.” In addition, it specifies, “In individuals with clinical ASCVD in whom high-intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated.”

“For patients identified within 1 of these groups, statin therapy, using either a high- or moderate-intensity agent, is recommended based on the specified group,” Dr. Saseen said.

The statin regimens recommended in the guideline as high-intensity (>50% average LDL cholesterol lowering) include atorvastatin (40 mg-80 mg) and rosuvastatin (20 mg-40 mg). Moderate-intensity statin regimens (30%-49% average LDL cholesterol lowering) include atorvastatin (10 mg-20 mg), rosuvastatin (5 mg-10 mg), simvastatin (20 mg-40 mg), pravastatin (40 mg-80 mg), lovastatin (40 mg), fluvastatin (80 mg), and pitavastatin (2 mg-4 mg).

Among the other issues raised in the new guidelines was the use of nonstatin drugs.  Dr. Saseen emphasized that the panel found no data to support the routine use of nonstatin drugs combined with statin therapy to reduce further ASCVD events. However, he said the panel thought it was reasonable to use nonstatin cholesterol-lowering drugs to reduce ASCVD events in individuals who are completely intolerant to statins if the evidence from randomized clinical trials shows that the benefits outweigh the potential adverse effects.

Another issue Dr. Saseen discussed was the panel’s recommendation on statin safety. The guidelines recommend using moderate-intensity statin therapy in patients with whom high-intensity therapy is recommended but who are predisposed to adverse effects, such as individuals with multiple or serious comorbidities, those with previous statin intolerance or muscle disorders, those with unexplained alanine transaminase elevations >3 times the upper limit of normal range, those ≥75 years of age, or those who have characteristics or concomitant use of drugs affecting statin metabolism.

Dr. Saseen emphasized that, despite the lack of support by some organizations on the treatment approach represented in the guidelines, he thinks the recommendations are evidence-based and “represent a reasonable proven approach to reducing risk of cardiovascular events.”—Mary Beth Nierengarten