At a session at Internal Medicine 2014, held in Orlando, Fla., in April, Michelle A. Albert, MD, MPH, offered insight into the 2013 American College of Cardiology Foundation/American Heart Association guideline on treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.
According to the guideline, 4 groups of patients, 2 primary prevention groups and 2 secondary prevention groups, can benefit from statin therapy, noted Dr. Albert, who is chair of cardiovascular medicine and director of cardiovascular research at Howard University College of Medicine in Washington, D.C., and adjunct professor of medicine at Johns Hopkins University in Baltimore.
Statins can be used as primary prevention in patients with diabetes who are between 40 and 75 years of age with low-density lipoprotein (LDL) cholesterol levels of 70 to 189 mg/dL, as well as in patients 40 to 75 years of age without diabetes who fall into the high-risk group for atherosclerotic cardiovascular disease (ASCVD), defined by the guideline as a 10-year risk of at least 7.5%. Also, statins can be used for secondary prevention in patients with clinical ASCVD and in patients 21 years of age or older with an LDL cholesterol level of 190 mg/dL or greater.
Focus on intensity
The guideline authors pointed out that there is lack of evidence from randomized, controlled trials to support titration of drug therapy to specific LDL cholesterol and/or non-HDL cholesterol goals, Dr. Albert said, while evidence supports appropriate intensity of statin therapy.
“The focus of the cholesterol guidelines [is] on intensity of statin therapy and not so much targeting an LDL cholesterol level, and also quantitative comparison of statin benefits with statin risk,” she said. She also noted that LDL cholesterol is a surrogate biomarker of CVD risk but does not encompass the total risk profile related to plaque rupture. “Something like non-HDL cholesterol may actually be a better assessment of rupture risk,” Dr. Albert said.
The guideline recommendations for statin initiation to reduce ASCVD risk are “pretty simple, actually, and probably again is not that different from what you have been doing in your practice,” she said. “The core of the guideline is lifestyle habits, making sure you exercise and you eat a balanced diet, among other things,” before statins are started.
Dr. Albert noted that decisions about statin type are related to age in adults who have clinical atherosclerotic disease. High-intensity statins, those that reduce LDL cholesterol level by more than 50%, are recommended for secondary prevention in patients age 75 or younger, and moderate-intensity statins, those that reduce LDL cholesterol by 30% to 50%, are recommended in those older than age 75 and in those in whom high-intensity statins can't be used. High-intensity statins are also recommended in patients with LDL cholesterol levels in the high-risk range, that is, 190 mg/dL or greater.
Diabetic patients can receive moderate-intensity statins unless their 10-year risk of ASCVD is considered to be 7.5% or greater, Dr. Albert said. She also noted that 80-mg doses of simvastatin are no longer recommended by the FDA because of side effects, specifically myopathy.
When considering primary prevention, Dr. Albert said, there's some debate about whether 10-year risk or lifetime risk should be considered. Evidence suggests that the new guidelines and risk calculator potentially overestimate 10-year risk in primary prevention. Critics point to large primary prevention studies, external validation data, and miscalibration in support of the contention of risk overestimation in large numbers of healthy people, Dr. Albert stated. The guideline authors, she said, recommend estimating 10-year atherosclerotic disease risk by using the new pooled cohort risk equations, which they feel have been improved by the inclusion of race and sex.
The guideline also aimed to more accurately identify higher-risk patients who will benefit from statin therapy, Dr. Albert said. She noted that clinicians may want to consider avoiding initiation of statin therapy in high-risk groups who have not been found to benefit, such as patients with more severe heart failure and those with renal failure.
Balancing benefit with risk
Before initiating statin therapy, clinicians and patients should discuss the potential for benefits of risk reduction for ASCVD, potential for adverse effects, drug-drug interactions, and patient preferences, Dr. Albert said. In patients for whom a risk decision is uncertain, she said, the following factors may help inform clinical decision making:
- family history of premature ASCVD, or “anybody who has a family member who's had CVD at less than age 50, and in African-Americans that can shift about 5 years lower”;
- elevated lifetime risk for ASCVD;
- LDL cholesterol level of 160 mg/dL or greater;
- high-sensitivity C-reactive protein level of 2.0 mg/dL or greater;
- a coronary artery calcium score of at least 300 Agaston units; and
- an ankle-brachial index less than 0.9.
When clinicians are prescribing statins, the guideline recommends that they avoid focusing on LDL cholesterol or non-HDL cholesterol levels as treatment goals, although a lipid panel should still be obtained to monitor adherence, Dr. Albert said. In addition, clinicians should use medications proven to reduce ASCVD risk and should discuss benefits and harms for each individual patient, emphasizing optimal lifestyle and allowing appropriate shared decision making.
Therapeutic response to statin therapy and safety should be regularly assessed, Dr. Albert said. This should include a fasting lipid panel performed within 4 to 12 weeks after initiation or dose adjustment and every 3 to 12 months thereafter. Other safety markers should be measured as clinically indicated, Dr. Albert said. In patients who are candidates for statin treatment but who are statin-intolerant, it is reasonable to use non-statin cholesterol-lowering drugs that have been shown to reduce ASCVD risk in randomized, controlled trials if the ASCVD risk reduction benefits outweigh the potential for adverse events, she noted.
Dr. Albert reminded her audience that adherence to medications is an important piece of the puzzle and part of the focus of the new guidelines.
“When you start somebody on a medication, [it's] not so much focusing on a target, not so much focusing on ... other issues around therapy, but really focusing on benefit, focusing on things like adherence, and ensuring that people are actually taking their meds and ensuring that they're actually decreasing their global risk,” she said.