Reference: Circulation 2026 Mar 13 early online
Practice Points: The American College of Cardiology (ACC) / American Heart Association (AHA) released updated guidance on managing dyslipidemias that differs meaningfully from prior guidance, representing a clear paradigm shift toward lifetime atherosclerotic cardiovascular disease (ASCVD) risk management. Below is a concise summary of key clinical practice points, followed by a more detailed, evidence‑based discussion highlighting what changed from the 2018 guideline, and why.
- Check lipids (nonfasting or fasting) every 5 years starting at age 19; screen all children once between ages 9-11.
- Use the PREVENT-ASCVD equations to estimate 10- and 30-year risk.
- Classify 10-year PREVENT-ASCVD risk as low (< 3%), borderline (3% to < 5%), intermediate (5% to < 10%), or high (≥ 10%).
- Use coronary artery calcium (CAC) scoring to reclassify borderline or intermediate‑risk patients when treatment decisions are uncertain. Statin therapy may be deferred for CAC = 0. CAC > 0 generally favors statin initiation; higher CAC scores (≥ 100 or ≥ 75th percentile) support high‑intensity therapy.
- Initiate LDL‑C-lowering therapy earlier and for longer durations to reduce cumulative atherogenic exposure. Consider pharmacotherapy at borderline risk (> 3%), and recommend statins for intermediate or higher risk (≥ 5%). Use higher-intensity statins for higher-risk patients.
- Treat to LDL‑C goals: < 100 mg/dL for low, borderline, or intermediate risk, < 70 mg/dL for high risk, and < 55 mg/dL for very high‑risk ASCVD (secondary prevention), with non‑HDL‑C goals 30 mg/dL higher.
- If lipid targets are not met with statins alone, consider measuring apolipoprotein B and lipoprotein(a) and add nonstatin therapies such as ezetimibe or PCSK9 inhibitors in whatever sequence makes the most sense for the patient (no longer fixed).
Screening starts sooner and is universal. Universal lipid screening with a nonfasting or fasting lipid panel is now recommended every 5 years starting at age 19, along with a one‑time screening in childhood between ages 9-11. This represents a departure from the largely risk‑based approach of prior guidelines and reflects mounting evidence that cumulative exposure to atherogenic lipoproteins drives lifetime ASCVD risk, not just individual events.
This shift was influenced by rising rates of obesity, diabetes, and premature myocardial infarction in young adults as well as long‑term observational data. The CARDIA study, which followed young adults initially enrolled at ages 18-30, demonstrated that even modest reductions in LDL-C in young adulthood translated to clinically important reductions in ASCVD events over the next 16-20 years. Importantly, these associations persisted after adjustment for traditional risk factors, supporting the idea that earlier LDL‑C lowering confers lasting benefit.
Universal childhood screening may seem like more of a stretch at first glance, bringing up questions like “Have those recommending universal screening for children ever borne witness to trying to get labs from a child?” However, there is actually some new evidence that universal screening improves detection of familial hypercholesterolemia (FH), which affects about 1 in 250 children. The most compelling data come from a 20-year follow-up study of 214 children with heterozygous FH who initiated statin therapy in adolescence: By age 39, 99% were cardiovascular disease-free, compared with 74% of their affected parents, who did not have access to statins until adulthood. Impractical recommendation or not, that magnitude of benefit is difficult to ignore. That said, equipoise remains. As of its most recent review, the USPSTF still concludes that evidence is insufficient to show that universal lipid screening in children directly reduces cardiovascular events or mortality, an uncertainty acknowledged by the guideline and worth flagging.
Risk assessment got an upgrade with PREVENT. The Predicting Risk of Cardiovascular Disease Events (PREVENT) equations replace the Pooled Cohort Equations (PCEs) for estimating both 10‑ and 30‑year ASCVD risk in adults aged 30-79. Several differences are clinically meaningful:
- Borderline risk now starts at 3% (not 5%), lowering the threshold at which lipid-lowering pharmacotherapy may be considered. 10-year PREVENT-ASCVD risk is classified as low (< 3%), borderline (3% to < 5%), intermediate (5% to < 10%), or high risk (≥ 10%).
- PREVENT excludes race and incorporates kidney function, A1c, and measures of social deprivation.
- PREVENT estimates both ASCVD and heart failure risk, which better reflects the real-world scope of cardiovascular disease.
Unlike the PCEs, which do not generate estimates for adults under 40 and are known to overestimate risk in current-day populations, PREVENT has demonstrated improved calibration and discrimination across derivation and external validation cohorts and allows more informed decision-making in younger adulthood, leaving more time to address cumulative exposure to lipoproteins.
Treatment is recommended sooner and for a longer duration. For primary prevention, statin therapy is now considered reasonable at borderline risk (3% to < 5%) and is recommended at intermediate risk (5% to < 10%), of course following a discussion between the patient and provider. The higher the PREVENT-ASCVD risk, the stronger the recommendation and the higher the suggested statin intensity.
Importantly, the relevant treatment window has expanded to ages 30-79, compared with 40-75 in the 2018 guideline. In addition, at least moderate-intensity statin therapy is also recommended regardless of calculated risk for adults aged 40-75 with diabetes, CKD stage 3-4, or HIV.
Statin therapy may also be considered for adults aged 30-59 who are at low 10‑year risk (< 3%) but have a 30‑year risk ≥ 10% and LDL‑C 160-189 mg/dL, reinforcing the guideline’s emphasis on long‑term risk exposure rather than short‑term event prediction and prevention.
These broader treatment thresholds are supported primarily by a large meta‑analysis (but no new trials) which demonstrated statistically significant ASCVD risk reduction even among lower‑risk individuals treated with statins. In that analysis, a 10‑year risk threshold near 3% marked the point at which anticipated benefit exceeded potential harms. The same meta-analysis, albeit of still somewhat limited data in older adults, also suggested ongoing benefit beyond age 75, helping justify longer treatment duration in selected older adults, again, after discussion with the patient.
Treatment in children should start sooner, too. For children with LDL-C ≥ 160 mg/dL, early statin therapy should be considered, especially when accompanied by risk enhancers such as heterozygous FH, family history or premature ASCVD, elevated lipoprotein(a), or diabetes. These recommendations do not apply to children with homozygous FH, for whom statins are recommended from the time of diagnosis (which is often in infancy) as part of combination therapy.
On a sort-of related note, while statins are no longer absolutely contraindicated by the FDA in pregnancy, the ACC/AHA continues to recommend discontinuation during pregnancy except in rare, very high‑risk cases.
Coronary artery calcium (CAC) reclassification is recommended for borderline or intermediate-risk patients when uncertainty exists about statin initiation. High-quality evidence supports the reliability of CAC to meaningfully reclassify risk. Up to 40% of intermediate-risk individuals (5%-10%) have a CAC score of 0, making CAC a powerful downward reclassifier (music to the ears of those who lean toward doing less). On the flip side, 25% have CAC ≥ 100, with event rates comparable to high-risk patients, clearly favoring statin initiation, often at a high intensity.
LDL-C (and non-HDL-C) treatment goals are back. After a decade without numeric targets, the guideline brings back absolute LDL‑C and non‑HDL‑C goals to guide therapy.
- For primary prevention, target LDL‑C < 100 mg/dL for patients at borderline or intermediate risk and LDL‑C < 70 mg/dL for patients at high risk.
- For secondary prevention (very high risk), target LDL‑C < 55 mg/dL.
Non‑HDL‑C targets remain 30 mg/dL higher than corresponding LDL‑C targets.
This shift reflects accumulating randomized trial evidence showing that achieved LDL‑C levels, not just percentage reductions, correlate with reduction in major coronary events, independent of baseline LDL‑C, across both primary and secondary prevention populations. For secondary prevention especially, lower really does seem to be better.
There are more options for nonstatin therapy and flexibility with sequence of use. For patients who are statin‑intolerant or require additional agents to achieve LDL‑C reduction, several nonstatin therapies now have high-quality outcome data and strong guideline support.
Bempedoic acid demonstrated ASCVD event reduction in statin‑intolerant patients, with efficacy approaching that of moderate‑intensity statins, although it is associated with increased risk of gout, tendon rupture, and elevated uric acid.
Ezetimibe and PCSK9 inhibitors, including monoclonal antibodies such as evolocumab (Repatha), alirocumab (Praluent), and inclisiran (Leqvio), remain effective options with demonstrated LDL‑C lowering and cardiovascular benefit when added to statins in high‑risk patients. Ezetimibe is now generic, and even some of the newer drugs are more accessible with lower cost, broader formulary coverage, or through manufacturer coupons.
Notably, ezetimibe is no longer required to precede PCSK9 inhibitors when therapy intensification is needed. The 2026 guidelines now support therapy selection based on the degree of LDL-C reduction needed, tolerability, cost, and patient preference.
Consider measuring apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)] to guide treatment intensification. ApoB measurement is reasonable once LDL‑C and non‑HDL‑C are at or near goal, particularly in patients with diabetes, hypertriglyceridemia, or suspected residual risk. Every atherogenic particle (LDL, VLDL, IDL, and Lp[a]) carries exactly one ApoB molecule, making ApoB a direct measure of total plaque‑forming particle burden, which is sometimes more informative than the data from a standard lipid profile alone.
The guideline recommends that Lp(a) should be measured at least once in a lifetime for all adults. Lp(a) is a genetically determined, highly atherogenic lipoprotein and represents an independent ASCVD risk factor. (If it helps: The “a” in Lp(a) = apple doesn’t fall far from the tree.)
When Lp(a) is ≥ 125 nmol/L, risk is meaningfully higher regardless of LDL‑C level. While no medications are currently approved to specifically target Lp(a), the guideline recommends intensifying LDL‑C lowering and aggressively managing all other modifiable risk factors. PCSK9 inhibitors may be particularly useful in this context, given their modest but consistent Lp(a)‑lowering effect.
What stays the same? Statins are still the mainstay of lipid-lowering therapy, lifestyle modification continues to be emphasized, and shared decision-making remains central to treatment decisions, especially for primary prevention.
For more information, see the topic Hypercholesterolemia in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Executive Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Senior Clinical Writer at DynaMed; Claire Symanski, PhD, Medical Editor and Team Lead for ENT at DynaMed; Michael Butler, PhD, Medical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.