Despite its treatability, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality globally. “Modifying cholesterol is one of the most important things we can do in patients with established ASCVD or those without ASCVD but at high risk,” says Duke cardiologist Nishant P. Shah, MD. “Many studies have shown the lower your LDL cholesterol, the better your outcome, the less likely you are to have an initial or recurrent cardiac event: the lower, the better.”

Although 70 mg/dL is the general threshold for LDL cholesterol (LDL-C) treatment, new American College of Cardiology/American Heart Association guidelines, released in March 2026, recommend LDL-C levels less than 55 mg/dL for very high-risk patients with a history of ASCVD. Early treatment and intensively addressing LDL cholesterol (LDL-C) are vital to address ASCVD risk.

Physicians are vital to increasing compliance, a key challenge. “Many patients don’t understand why they’re on certain medications nor that these medications could be lifelong,” says Shah. “Some patients self-discontinue statin therapy or assume they don’t need it anymore. It’s important that patients and providers have a discussion where the patient is fully informed on what they’re taking, why they’re taking it, and what goals we’re looking for on the medication.”

The problem is also systemic. In a recent study published in Circulation: Population Health and Outcomes, Shah examined information from 1.7 million patients with ASCVD across 16 health systems. On average, 57.5% of patients with data available had LDL-C above 70 md/dL despite treatment. “We need innovative implementation strategies to improve cholesterol across a health system,” Shah says.

Lifestyle modifications are foundational to lower LDL-C, including exercise and a heart-healthy diet. “But for some people, lifestyle modifications alone are not enough to get to their specific LDL goal,” Shah says. Backed with solid clinical evidence, statin therapy is usually the first line. When statins are insufficient or not well tolerated, further medical options include:

• Ezetimibe, daily oral medication, can lower LDL-C up to 30%
• Evolocumab and alirocumab, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors injected bi-monthly
• Inclisiran, PCSK9 inhibitor injected up to twice a year
• Bempedoic acid, daily oral medication, which can also be taken with ezetimibe to increase its effectiveness

Shah also helps patients with their cholesterol goals at the Duke Cardiometabolic Prevention Clinic. “If providers feel unsure on how low to make patients’ cholesterol, or they’re having difficulty getting the cholesterol under control, or a patient would like to know more, please send them to us,” Shah says. “The clinic is more than happy to assist referring providers in the community to improve their patients’ cardiovascular risk factors.”