CHOLESTEROL GUIDELINES

Coupled with the guideline changes—the most surprising of which was abandoning LDL-cholesterol targets in favor of identifying four specific groups of patients who benefit from moderate- or high-dose statin therapy—the cholesterol scene is made complicated because other clinical guidelines, including those from Europe and Canada, also offer advice on treating patients at risk for atherosclerotic cardiovascular disease (ASCVD).

Given the confusion and controversy, Dr Pamela Morris(Medical University of South Carolina, Charleston) and colleagues published a state-of-the-art review of the clinical practice guidelines for the management of LDL-related risk in the July 15, 2014 issue of the Journal of the American College of Cardiology ^[1].

In it, they summarize the existing clinical guidelines of the ACC/AHA, the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), the Canadian Cardiovascular Society (CCS), and the International Atherosclerosis Society (IAS), as well as clinical guidelines for the management of lipids in women, children, adolescents, and those with diabetes or chronic kidney disease (CKD). In doing so, they attempt to provide a clear picture of the guidelines' differences and similarities.

"It can be very confusing for healthcare providers," said Morris. "When I have a patient in my office, and it's a Hispanic woman who might have a little bit of renal insufficiency, what do I do? Do I follow the AHA guidelines for women, do I look to the CKD guidelines, or do I go to the ACC/AHA guidelines? There is some confusion regarding the multitude of available guidelines, and this confusion can result in suboptimal care of LDL-related risk."

Speaking with heartwire , Morris said that when she is speaking with other clinicians about the old and new clinical guidelines, the myriad of recommendations leads many of them to simply stay the course.

"They're doing the exact same thing they've always been doing," she said. "It's a barrier to change. So, hopefully, an article like this will help them understand previous guidelines and why the new guidelines were formulated. It will also help them understand that there are some similarities with the new guidelines, as well as some differences. I think if we can put it all in context, it might help them begin to implement new recommendations into their practice."

ACC/AHA Guidelines Launched in November 2013Reported by heartwire when they were published and later criticized, the ACC/AHA cholesterol guidelines recommend physicians treat four major primary- and secondary-prevention patient groups with statins. These four groups were selected because randomized, controlled clinical trials showed that the benefit of treatment outweighed the risk of adverse events. The four groups include:

• Individuals with clinical atherosclerotic cardiovascular disease.
• Individuals with LDL-cholesterol levels >190 mg/dL, such as those with familial hypercholesterolemia.
• Individuals with diabetes aged 40 to 75 years old with LDL-cholesterol levels between 70 and 189 mg/dL and without evidence of ASCVD.
• Individuals without evidence of ASCVD or diabetes but who have LDL-cholesterol levels between 70 and 189 mg/dL and a 10-year risk of ASCVD >7.5%.

The guidelines also recommend either moderate- or high-dose statin therapy, depending on the patient's risk. Those with ASCVD, for example, should be treated with a high-dose statin, such as atorvastatin 80 mg or rosuvastatin (Crestor, AstraZeneca) 40 mg, to achieve a 50% reduction in LDL-cholesterol levels.

To heartwire , Morris noted that while the new ACC/AHA practice guidelines abandon specific treatment targets, LDL remains the target of therapy, something it has in common with the other clinical guidelines. The majority of other practice guidelines continue to treat to specific LDL-cholesterol targets depending on patient risk and utilize low-dose statin therapy in certain patients (the US guidelines recommend low-dose statins only in those with a high risk of statin-related adverse events).

"LDL is still the lipoprotein of interest," said Morris of the 2013 ACC/AHA practice guidelines. "There might be variations in how you measure it. The big difference now is that there are no longer goals for how low to get it. And this is really unique to two sets of guidelines. It's unique to the ACC/AHA guidelines, and interestingly it's also a part of the new CKD guidelines, the new [Kidney Disease: Improving Global Outcomes] KDIGO guidelines. Again, in those guidelines, you start statin therapy at a fixed dose and there is no LDL-cholesterol goal."

New Risk Assessment Tool

In addition to coming under fire from those who believed the new guidelines opened the floodgates to treating more and more individuals with statins, especially those without ASCVD, the ACC/AHA guidelines had a rocky launch when two independent researchers reported that the algorithm used to assess the 10-year risk of ASCVD overestimated risk by 75% to 150% in three cohorts. The new risk-assessment calculator departs from the Framingham Risk Score (FRS) and was developed by an ACC/AHA expert panel who authored the 2013 guidelines for the management of patient risk.

"I think this change is important, that we now have a brand-new risk assessment tool," said Morris. "For decades we've been using different iterations of the Framingham Risk Score, whether it's the 10-year risk or lifetime risk. The new risk-assessment tool does have some limitations in terms of ethnic groups. It applies only to non-Hispanic whites and non-Hispanic African-Americans."

On the whole, however, the use of different risk calculators across the different guidelines makes sense, said Morris. These calculators should be tested and validated in the group of patients to which they are being applied.

Other Forms of Dyslipidemia

To heartwire , Morris said the older ATP III guidelines addressed how to treat most forms of dyslipidemia, including patients who would require a statin plus another LDL-lowering agent, such as cholesterol absorption inhibitors, bile-acid sequestrants, LDL apheresis, or newer drug therapies. The 2013 ACC/AHA guidelines are simplified and focus entirely on managing ASCVD risk caused by LDL cholesterol. Morris said this is appropriate given that this is where researchers have accumulated the most evidence. For example, there is very limited evidence supporting raising HDL or lowering triglycerides alone for the reduction of cardiovascular outcomes, she said.

The American Association of Clinical Endocrinologists (AACE) and the National Lipid Association(NLA) do not support the ACC/AHA guidelines, instead recommending that their members follow their own clinical guidelines for the management of cholesterol and CVD risk.

While Morris said she couldn't speak to why these two societies chose not to endorse the 2013 ACC/AHA guidelines, she suspects they still believe that treating to lower and lower goals still offers meaningful clinical benefits to the patient. In contrast to the ACC/AHA guidelines, which focused on randomized, controlled clinical trials only to support the recommendations, clinical lipidologists will often cite the totality of evidence, including animal and pathophysiologic studies of atherosclerosis, supporting lower LDL-cholesterol targets to decrease the risk of cardiovascular events.