LDL Control Remains Poor in CAD Patients: NHANES

The majority of US patients with CAD are not being treated to the recommended LDL cholesterol targets outlined in clinical guidelines, according to an analysis of the National Health and Nutrition Examination Survey (NHANES).

Many patients aren’t even being treated with a statin, report investigators, and this translates into nearly three-quarters of adults with CAD exceeding the recommended LDL cholesterol target of 70 mg/dL.

“Even in a relatively contemporary era, there’s still about one in three adults with coronary artery disease who aren’t receiving statin therapy,” senior investigator Deepak Bhatt, MD, MPH (Icahn School of Medicine at Mount Sinai, New York), told TCTMD. “If we talk about things like ezetimibe, only 6.4% were receiving it. That is a really low rate [of use] of both of those and it’s reflected in rather poor LDL control.”  

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of cholesterol recommend that all patients with atherosclerotic cardiovascular disease (ASCVD) be treated with a high-intensity statin with the aim of reducing LDL cholesterol levels by 50% or more. The ACC/AHA guidelines have moved away from hard LDL targets, but they still recommend adding a PCSK9 inhibitor or ezetimibe in very-high-risk patients with LDL cholesterol levels 70 mg/dL or higher.

The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines take a stricter line with cholesterol targets, recommending that all high- and very-high-risk patients be treated to LDL cholesterol levels of < 70 and 55 mg/dL, respectively.

‘Perplexing’ State of Affairs

In the new analysis, which was published as a research letter July 3, 2022, in JAMA, researchers led by Rahul Aggarwal, MD (Brigham and Women’s Hospital, Boston, MA), evaluated lipid control between 2015 and 2020 among 5,862 US adults enrolled in NHANES. Of these, 472 adults (mean age 64.5 years; 40.5% women) had a diagnosis of CAD.

Among those with CAD, of whom 67.9% were taking a statin, the mean age-adjusted LDL cholesterol level was 94.4 mg/dL. In total, 73.5% of adults with CAD had LDL cholesterol levels 70 mg/dL or greater. In the statin-treated patients, the mean age-adjusted LDL cholesterol level was 82.2 mg/dL. In these patients, 65.2% had LDL cholesterol levels 70 mg/dL or greater and 83.3% had levels 55 mg/dL or greater.

For the patients with CAD not taking a statin, only 10.9% were taking ezetimibe. In this group, the age-adjusted LDL cholesterol level was 120.4 mg/dL, with 91.0% and 98.2% of patients having LDL cholesterol levels ≥ 70 and 55 mg/dL, respectively.

The low rate of achieving guideline goals for LDL cholesterol is concerning, said Bhatt. While the reasons may be multifactorial, one reason typically cited for the lack of compliance to medical therapy is the cost of drugs, but that doesn’t apply here. “We’re talking about generic statins and generic ezetimibe,” he said. Side effects from statins—whether real or perceived—might be a contributing factor, but that shouldn’t be the case with ezetimibe, which is reasonably effective but has an excellent safety profile, he said.

“It’s a bit perplexing that these relatively inexpensive, easy measures aren’t being used more,” said Bhatt. “Medicine has to do a better job at getting physicians to use therapies that are effective and really safe.” 

Prior studies have also demonstrated that European physicians aren’t faring much better at getting patients to LDL cholesterol goals.  

Physician and Patient Education

In terms of efforts to improve LDL cholesterol levels, as well as the percentage of patients at goal, Bhatt said more physician education is necessary, particularly with ezetimibe. There are data from IMPROVE-IT showing the drug modestly lowers the risk of major cardiovascular events (it does not have a US Food and Drug Administration indication for cardiovascular event reduction), but the drug is no longer aggressively marketed to physicians after Merck, the manufacturer, lost patent protection in 2017.

While physician education, particularly with primary care doctors, would be helpful to increase statin prescribing, a patient-education campaign would also be beneficial, Bhatt said.

Statins have such a bad reputation online that it “would be hard to really undo” without a massive educational effort, he noted. For the truly statin intolerant, there are other options, among them the PCSK9 inhibitors alirocumab (Praluent; Sanofi/Regeneron) and evolocumab (Repatha; Amgen), inclisiran (Leqvio; Novartis), and bempedoic acid (Nexletol; Esperion). These drugs could be used in statin-intolerant patients if ezetimibe is insufficient to get patients to the recommended LDL cholesterol goals, he said.

One of the challenges of treating stable CAD patients is that many “feel well” in the outpatient setting, which can make it difficult to convince patients they need to be on lifelong medical therapy with statins, ezetimibe, or other drugs, said Bhatt.  

“It probably points to the fact that maybe we really do get more aggressive in terms of risk factor control when we do have patients in the hospital, when we have their attention,” he said. “If that intense LDL control isn’t started in the hospital, a lot of times, as we’re seeing here, it doesn’t get started.”

There is also a need for education about the importance of continuing therapy, said Bhatt, noting that rates of statin discontinuation in acute MI patients are as high as 50% after 1 year.