ACC/AHA Guidelines Still Stirring Up Discussion, Questions

Boston—Since the 2013 American College of Cardiology (ACC) and American Heart Association (AHA) joint guidelines were published, debate has ensued [Circulation. 2013;129(25 suppl 2):S1-S45]. “From the get-go they had criticism from the approach they took,” said R. Scott Wright, MD, FACC, FESC, FAHA, professor of medicine, division of cardiology, Mayo Clinic, during a satellite symposium at the AMCP meeting, detailing new therapies for hypercholesterolemia. The session was supported by an educational grant from Sanofi US and Regeneron Pharmaceuticals.

Guideline Updates
In summation, changes made in the 2013 ACC/AHA guidelines included:
• No specific treatment goals for low-density lipoprotein (LCL) cholesterol and non–high-density lipoprotein (HDL) cholesterol
• Statins classified as high-, moderate-, or low-intensity (Table)
• Four distinct groups targeted for treatment with statins
• Nonstatin therapies de-emphasized
• Guidelines recommended only for adults 40 to 75 years of age
• New risk tool—Cardiovascular (CV) Risk Calculator—was implemented to replace the Framingham Risk Score
• No guidelines for high triglycerides

Dr. Wright noted that another task force has already been convened for a new set of guidelines. He said particular criticism has arisen from multiple areas. For example, with no specific LDL and non-HDL goals, physicians have no goal to track patient progress on; therefore, they can no longer be penalized for not getting patients to goal. In addition, many have expressed concern over the CV Risk Calculator, which Dr. Wright agreed, “I think criticisms were very fair. [This is a] new tool that was not peer-reviewed.”

The 4 major groups targeted for statin treatment according to the guidelines include: (1) individuals with atherosclerosis cardiovascular disease (ASCVD), who should be treated with high-intensity statins if they are ≤75 years of age or moderate-intensity statins if they are >75 years of age; (2) individuals with LDL >190 mg/dL, who should be treated with high-intensity statins; (3) individuals with diabetes and those between 40 and 75 years of age with LDL cholesterol levels of 70 mg/dL to 189 mg/dL, who should be treated with moderate-intensity statins if they have a low risk of ASCVD <7.5% or treated with high-intensity statins if they have a high risk of ASCVD >7.5%; and (4) individuals without clinical ASCVD or diabetes but those with LDL cholesterol levels of 70 mg/dL to 189 mg/dL and an estimated 10-year ASCVD risk ≥7.5%, who should be considered for moderate- or high-intensity statins.

The guidelines also emphasize lifestyle modifications, including a heart healthy diet, regular exercise, avoidance of tobacco products, and maintaining a healthy weight. “Nothing trumps lifestyle,” said Dr. Wright.

Dr. Wright said that what this means for managed care is the National Committee for Quality Assurance will be retiring its Healthcare Effectiveness Data and Information Set measure in 2015 in order to align itself with the current ACC/AHA guidelines.

Weighing Treatment Options
Joanne M. Foody, MD, FACC, FAHA, executive director, Pollin Women’s Heart Center, Heart and Vascular Center, Brigham and Women’s Hospital, associate professor, Harvard Medical School, continued the presentation by discussing unmet needs that remain for CVD patients.

CVD continues to be the leading cause of death in the United States, accounting for >30% of all deaths and costing >$108 billion each year.

Despite effective treatments such as statins, many patients are not achieving optimal LDL cholesterol levels. According to the presentation, approximately 31.9 million adults ≥20 years of age have total serum cholesterol levels ≥240 mg/dL. In a study of 20,000 US veterans, 59% of very–high-risk patients were not reaching a LDL goal of <70 mg/dL. Additionally, in an analysis of 1249 patients with heterozygous familial hypercholesterolemia (FH), only 21% achieved a LDL treatment goal of <97 mg/dL on maximum statin treatment or combination therapy with ezetimibe.

Dr. Foody said 3 patient populations face unmet needs: (1) statin-intolerant patients; (2) statin-resistant patients; and (3) FH.

Dr. Foody said statin intolerance occurs in approximately 10% to 20% of patients and commonly results in treatment discontinuation. The FDA defines statin intolerance as treatment failure on 2 statins. Other than statins, existing therapies only provide modest LDL reduction. Statin-related adverse events commonly lead to discontinuation. Upward of two-thirds of patients report muscle pain as a serious adverse effect. In a national survey, 62% of statin users cited muscle pain as the primary reason for discontinuation. One-third of patients stopped treatment without asking or informing their provider. Dr. Foody suggested that clinicians perform a “muscle inventory” before beginning statin therapy. That way, clinicians and patients will have a baseline record of patient aches and pains prior to therapy so that can be eliminated as a possible side effect.

FH is also underdiagnosed and undertreated, with >600,000 US adults having FH, though <10% are diagnosed. FH causes early CVD and is difficult to treat. “We need to be more aggressively screening [for FH],” said Dr. Foody, mentioning that screening for FH is beginning to occur more by pediatricians.

New & Emerging Therapies
Newly approved lipoprotein synthesis inhibitors, including mipomersin and lomitapide, have already been approved for adjunctive use in patients with homozygous FH to further lower plasma LDL levels. These medications are expensive and carry Black Box Warnings for hepatotoxicity. An additional 2 classes are still in clinical trials: (1) CETP inhibitors; and (2) PCSK9 inhibitors.

CETP inhibits conversion of HDL to LDL by stopping the action of CETP. Dr. Foody said that better data on this class should be available in 2 to 3 years, which could result in a new therapy for patients.

PCSK9 inhibitors promote intracellular degradation of hepatic LDL receptor (LDL-R), thus preventing LDL-R recycling to cell surface, LDL-R population on cell surface, and LDL clearance from circulation. The inhibition of PCSK9 offers potential for enhancing the LDL lowering effects of statins. Dr. Foody estimated that outcomes data on PCSK9 inhibitors should be available in 2017 or 2018.—Kerri Fitzgerald