Lower LDL Levels, Starting Earlier in Life: New ACC/AHA Dyslipidemia Guidelines

Today, the American College of Cardiology (ACC) and American Heart Association (AHA), in partnership with multiple other societies, released new guidelines for the management of patients with dyslipidemia.

Gone are the pooled cohort equations that formed the basis of risk assessment for the better part of two decades, with the PREVENT risk calculator now taking center stage. There is a return to specific cholesterol goals absent from prior guidelines and a focus on the patient’s lifetime risk of atherosclerotic cardiovascular disease (ASCVD).

Like past guidelines, statins remain the cornerstone of pharmacotherapy, with other agents, such as ezetimibe and PCSK9 inhibitors, added as needed.

Measuring lipoprotein(a) is strongly recommended once during an adult’s lifetime, and apolipoprotein B  testing now has a clear pathway toward improving risk assessment and guiding treatment. Coronary artery calcium (CAC) testing recommendations have been strengthened, specifically for its use as “tie breaker” when treatment is uncertain.

“This is really a preventive cardiology document,” Roger Blumenthal, MD (Johns Hopkins University School of Medicine, Baltimore, MD), chair of the writing committee, told TCTMD. “It says dyslipidemia, but it’s so much more than that with all the advances in risk assessment, imaging, Lp(a), triglycerides, and many other things.”

The new guidelines, co-chaired by Pamela Morris, MD (Medical University of South Carolina, Charleston), and published simultaneously in JACC and Circulation, include top 10 take-home messages for physicians and a large section on what’s new from the last update 2018. Since then, several new lipid-lowering drugs have been approved by the US Food and Drug Administration: bempedoic acid (Nexletol; Esperion), inclisiran (Leqvio; Novartis), and evinacumab (Evkeeza; Regeneron).

One major message of the recommendations is to treat elevated cholesterol levels earlier in life to reduce lifelong risk, with an emphasis on counseling and optimizing lifestyle habits in young people. Starting earlier with statins is recommended in all adults with heterogenous familial hypercholesterolemia (FH) or those 30 years old and younger with LDL cholesterol ≥ 160 mg/dL, those with a strong family ASCVD history, and those with a high 30-year ASCVD risk based on the PREVENT calculator.

The goal is “to reduce the lifelong risk of prolonged exposure to atherogenic lipoproteins,” said Blumenthal. “Health behavior counseling should start in youth, and we want people to ideally improve their lifestyle so that they get their LDL cholesterol for primary prevention in the range of 100 [mg/dL] or less.”

This is how preventive cardiology is practiced in 2026. Christopher Cannon

Christopher Cannon, MD (Brigham and Women’s Hospital, Boston, MA), who wasn’t involved with the guidelines but who has been involved in several lipid-lowering trials, said the writing committee got it right with their recommendations. “A++,” he told TCTMD. “This is how preventive cardiology is practiced in 2026.” That there should be a broad shift toward lower cholesterol levels in all patients is appropriate and “that’s based on the evidence.”

Similarly, Steven Nissen, MD (Cleveland Clinic, OH), who also has done extensive research around lipid-lowering treatments, said the emphasis on risk over 30 years is a welcomed change.

“We’ve known for some time that the time-averaged LDL over your lifetime is the one of the strongest predictors of whether you’re going to get cardiovascular disease,” he told TCTMD. A younger person, “somebody who is 41 years old, is not going to have much of a 10-year risk, so do you wait until they have manifest disease before you treat them? Or do you treat them before they have manifest disease?”

Preventive cardiologist Thais Coutinho, MD (Mayo Clinic, Rochester, MN), also agreed with the focus on getting cholesterol levels low earlier in life.

“I have always felt quite uncomfortable in cardiology, because we tend to twirl our thumbs and wait until there’s a signal of a problem before we treat,” she told TCTMD. “Once the plaque develops in your arteries, we can’t really remove that.” In prevention, the goal should be to set people up to have the healthiest lifestyle, and if they need it, pharmacotherapy, early in life because “it’s not just increased cholesterol or increased triglycerides, but it’s also the time under that higher level,” she said.

Primary Prevention

The new guidelines address treatment for patients with and without ASCVD. In the primary prevention setting, recommendations are broken out by patient risk estimated by the PREVENT calculator.

In low-risk patients (< 3%) based on the 10-year timeline who have an LDL cholesterol level between 160 to 189 mg/dL, or those with a 30-year risk of 10% or higher, a moderate-intensity statin is considered a reasonable approach (class 2a recommendation). If baseline LDL is less than 160 mg/dL in low-risk patients, and 30-year risk is less than 10%, only counseling on health behaviors is advised (class 1 recommendation).   

For those at borderline (3% to < 5%) and intermediate (5% to < 10%) risk, lipid-lowering therapy can be considered based on clinical judgement and discussions with the patient. In the borderline group, the LDL cholesterol target is less than 100 mg/dL, and if treatment is decided upon, moderate-intensity statin therapy is recommended (class 2a recommendation). For the intermediate-risk patient, either a moderate- or high-intensity statin is considered reasonable based on clinical judgement (class 1 recommendation).

“This is the data we have from the clinical trials, but again it’s all going to depend on clinician-patient risk discussion,” said Blumenthal. “Some people might feel they want some time to really work on lifestyle factors whereas others are going to be more apt to think about pharmacotherapy sooner rather than later.”

For primary prevention patients at high risk, such as those with a 10-year risk > 10%, the LDL target is less than 70 mg/dL (class 2a recommendation). For this group, treatment begins with a high-intensity statin to achieve at least a 50% reduction in LDL cholesterol from baseline (class 1 recommendation).

It’s really about being in this for the long haul, and these guideline writers got that right. Steven Nissen

To TCTMD, Nissen said the recommendation to possibly treat patients with a 10-year risk as low as 3% to less than 100 mg/dL is a “huge shift” from prior guidelines, noting that some of these changes will potentially affect a lot of people in the United States. In his clinical practice, though, he already treats such patients, particularly if LDL cholesterol is elevated, say around 160 mg/dL, and they have a family history of premature heart disease. While their 10-year risk might be borderline, their lifetime risk is high, he said.  

“You may not need to give them an intensive dose of statin,” said Nissen. “Five milligrams of rosuvastatin in a 32-year-old might be just fine for the long term, whereas if you pick them up when they’re 55, you need to get them a lot lower in order to lower their long-term risk. Treating earlier is sensible. It’s really about being in this for the long haul, and these guideline writers got that right.”

The PREVENT calculator used for risk assessment is derived from a more contemporary cohort than the older PCE. As such, estimates are more closely aligned with observed rates, but thresholds defining low, intermediate, and high risk are lower than with the PCE. Coutinho said that physicians will have to adjust to the different risk thresholds, but like Nissen, she is already frequently having conversations with patients deemed borderline risk.    

“Medicine is not [always] black and white,” she said. “When it’s black and white, it’s easy, right? In this grey zone, that’s where it takes on a new lens with the patient’s preferences and values.”

Some patients in the borderline-risk category may want to do everything to avoid ASCVD, including changing their diet, lifestyle, and taking a statin. Others will focus on their low absolute risk or may have a preference not to be on medication.

“That discussion is important to inform how to consider the therapy for these patients,” said Coutinho. “Most importantly, I always talk to my patients [and tell them] that lipid-lowering therapies in general are really the tip of the pyramid. They work best, or sometimes may not be needed at all, if we get that base taken care of. The base of the pyramid is all the behavioral and lifestyle therapies that we know work well.”

Risk Enhancers

Like prior guidelines, the updated version includes multiple “risk enhancers” that can help sway treatment, including family history, higher-risk ancestry (eg, South Asian and Filipino, high polygenic risk score, and presence of other clinical conditions, such as cardiovascular-kidney-metabolic (CKM) syndrome or inflammatory diseases. Different biomarkers—high-sensitivity C-reactive protein, triglycerides, and Lp(a)—also can be measured and considered to guide treatment in those at borderline or intermediate risk.

The advice that Lp(a) should be measured once in a person’s lifetime is a new class 1 recommendation—it was listed as a risk enhancer in prior iterations—and aligns with current European and Canadian guidelines, as well as those from the National Lipid Association. Elevated Lp(a) levels (≥ 50 mg/dL) are an indication for more intensified LDL cholesterol lowering and management of other risk factors (class 1 recommendation).

[The goal is] to reduce the lifelong risk of prolonged exposure to atherogenic lipoproteins. Roger Blumenthal

In adults at intermediate risk for ASCVD, and some at borderline risk, CAC scoring has a class 1 recommendation to help make a treatment decision if there is uncertainty around starting lipid-lowering therapy. If the CAC score is above zero, it’s recommended to start treatment, particularly if the score is 100 AU or greater (class 1 recommendation). If there’s uncertainty around the intensity of lipid-lowering treatment in intermediate or high-risk patients, a CAC score could also be useful (class 2a recommendation).  

“We really tried to stress that this is the best tiebreaker,” said Blumenthal. “Both the absolute amount of coronary calcium and the standardized percentile based on age, sex, and race have prognostic importance.”

Unlike the 2013 and 2018 guidelines, the current version recommends treatment targets based on CAC scores. For those with CAC ≥ 100 to 999 AU, treatment with statin therapy is recommended to hit LDL and non-HDL cholesterol goals of < 70 and < 100 mg/dL, respectively (class 1 recommendation). For the patient with CAC ≥ 1,000 AU, the goal is at least a 50% reduction in LDL cholesterol and a target of less than 55 mg/dL (class 1 recommendation).

Cannon said the biggest change in his clinical practice in the past couple of years has been the use of CAC scoring to help stratify patient risk. The new guideline recommendations, including the direction around cholesterol targets based on CAC score, “align with how I and every other preventive cardiologist I know practice,” he said.

Additionally, there is a new recommendation for measuring apoB, which can be used to further risk stratify patients once LDL and non-HDL cholesterol goals are achieved, particularly for those with elevated triglycerides, diabetes, or CKM syndrome (class 2a recommendation).

Coverage around apoB testing has been spotty in the past, say the experts, but the hope is that guideline recommendations lead to changes in reimbursement.

Blumenthal said the guidelines overall emphasize the “CPR” model: calculate, personalize, reclassify, and reassess. “The PREVENT risk estimate is an educated guess,” he said. After calculating the 10- and 30-year risk score, there are multiple tests available to help physicians personalize patient risk, and then direct treatment, he said.  

Secondary Prevention

In secondary prevention, things have been tightened up, as well, such that the cholesterol goals for the very-high-risk patient with ASCVD are < 55 mg/dL for LDL and < 85 mg/dL for non-HDL. These are patients with two or more major ASCVD events, such as a prior MI or stroke, or those with a single major ASCVD event plus two other high-risk conditions, such as smoking, diabetes, or hypertension, among others.

To achieve this aggressive target in the very-high-risk ASCVD patient, the recommendation is to add ezetimibe and/or a PCSK9 inhibitor to maximally tolerated statin therapy (class 2a recommendation). It’s also reasonable to use inclisiran, with or without ezetimibe, if patients can’t tolerate or obtain a PCSK9 inhibitor or if they prefer less-frequent dosing (class 2a recommendation).  

While there might be some ASCVD patients considered just high risk, and in whom the target can be LDL < 70 mg/dL, most secondary-prevention patients should be treated to the less than 55-mg/dL goal, according to the guidelines.    

The LDL targets, which were eliminated in the 2013 US guidelines, are aligned with the European Society of Cardiology dyslipidemia guidelines, said Blumenthal.

Interestingly, the ACC/AHA guidelines were approved before the VESALIUS-CV trial was published. That trial, which included patients at high cardiovascular risk but without a prior MI or stroke, showed that adding the PCSK9 inhibitor evolocumab (Repatha; Amgen) to statin therapy reduced the risk of CHD deaths, MI, or stroke after taking LDL levels down to 45 mg/dL.

Blumenthal said there are cost implications to adding a PCSK9 inhibitor to statin therapy when ezetimibe is available as a generic medication. While VESALIUS-CV led to some calls to lower LDL levels down to 45 mg/dL in high-risk patients, Blumenthal said that’s a challenge, especially if patients are starting with baseline LDL levels around 130 mg/dL.

“It’ll be interesting to see what clinicians do, but clearly there’s a been higher uptake of PCSK9 inhibitor prescriptions in the US since the VESALIUS study,” he said.

Regarding the return of LDL targets, Nissen, Coutinho, and Cannon were all pleased, noting that many doctors never really abandoned treating to goal. “I believe we should treat to target,” said Nissen, noting he was critical of the decision to abandon them in 2013. “Physicians like it, patients like it, and it’s the right thing to do. They’ve got good scientific evidence around treating to these lower targets, and I think the guidelines got it exactly right.”

“It makes total sense,” said Cannon. “There’s plenty of trials, including the latest VESALIUS, that support this.” Coutinho added that treatment targets let patients know exactly where they stand in terms of how treatment is going.

Special Considerations

Finally, the guidelines also provide insight into some special considerations. For patients with stage 3-4 chronic kidney disease, intensive lipid-lowering therapy to achieve a target LDL < 55 mg/dL is a class 1 recommendation. Statin therapy is recommended for HIV patients aged 40 to 75 years who are on stable antiretroviral therapy, for those with cancer or a history of cancer, and for those with diabetes without ASCVD (all class 1 recommendations).  

For patients with hypertriglyceridemia, lifestyle is the bedrock of treatment. This includes weight loss of at least 5% body weight and 150 minutes or more moderate-intensity exercise each week.  

Among women with dyslipidemia who are planning a pregnancy, are pregnant, or are lactating, there are also directions around treatment, too. Coutinho said the recommendations around pregnancy are more nuanced than in the past. Historically, pregnancy meant a hard stop to lipid-lowering therapy, but now there is an aim to have a discussion around the woman’s ASCVD risks and benefits of treatment as well as suggested referrals to a dietician.

“They give a little bit more space for a discussion between the patient and the physician about what is the right thing to do while still acknowledging that the majority of patients when they become pregnant will stop the statin,” Coutinho said.