Latest VA/DoD cholesterol guideline broadens risk checks, steps up therapy

Clinical takeaway: Use PREVENT for primary-prevention risk assessment, consider CAC when treatment decisions remain uncertain, and intensify therapy beyond statin monotherapy for patients with established ASCVD who are at very high risk.

A major update to the VA/DoD lipid management guideline shifts cardiovascular prevention toward more personalized risk assessment and more intensive treatment for patients at greatest risk of cardiovascular events. The guideline, summarized in Annals of Internal Medicine, incorporates evidence through January 2025 and includes 24 recommendations for primary and secondary prevention.

For primary prevention, clinicians should use the PREVENT equations to estimate cardiovascular risk. If an intermediate- to high-risk result leaves the treatment decision uncertain, coronary artery calcium (CAC) testing may improve risk classification; routine CAC testing is discouraged in low-risk patients.

The panel also suggests measuring lipoprotein(a), generally once in a lifetime, to identify inherited risk not captured by standard lipids. Evidence remains insufficient for routine use of other risk markers, including apolipoprotein B and high-sensitivity C-reactive protein.

Moderate-intensity statins remain first-line primary prevention. At least moderate-intensity therapy is strongly recommended for adults with diabetes, LDL-C of at least 190 mg/dL, or 10-year cardiovascular risk of at least 10%; it is suggested for adults without diabetes whose LDL-C is below 190 mg/dL and risk is about 5% to less than 10%.

The panel suggests a moderate-intensity statin with low antiretroviral interaction potential for adults with HIV, even when estimated 10-year risk is below 5%. Baseline AST or ALT elevations less than three times the upper limit of normal should not prevent otherwise indicated statin treatment.

For secondary prevention, the guideline offers three options: a high-intensity statin, a moderate-intensity statin plus ezetimibe, or a moderate-intensity statin plus a PCSK9 inhibitor. Very-high-risk patients may need a high-intensity or maximally tolerated statin plus ezetimibe, a PCSK9 inhibitor, or both.

Very high risk includes an acute coronary syndrome or myocardial infarction within the past 12 months despite lipid-lowering therapy, recurrent acute coronary syndrome, MI, or stroke, or ASCVD with LDL-C of at least 70 mg/dL despite treatment. If therapy drives LDL-C below 30 mg/dL, the panel suggests continuing it; evidence is insufficient to favor a treat-to-target approach over fixed-dose high-intensity statin therapy.

Icosapent ethyl is suggested for secondary prevention when fasting triglycerides remain at least 150 mg/dL on statin therapy, but evidence is insufficient for primary prevention. The panel advises against adding fibrates to statins and against omega-3 supplements or formulations other than icosapent ethyl.

For statin-associated symptoms, try a washout followed by rechallenge with the same or another statin, a lower dose, then intermittent dosing. If no statin is tolerated, options include bempedoic acid, ezetimibe, a fibrate, or a PCSK9 monoclonal antibody inhibitor.

The authors acknowledge remaining uncertainty: “At what risk level the benefit of statins disappears is unclear.” Shared decision-making remains important, particularly for intermediate-risk patients and when choosing among secondary-prevention regimens.

The guideline also supports a Mediterranean diet, sustainable aerobic activity, and structured cardiac rehabilitation after recent coronary disease.

What’s changed

• PREVENT replaces the nonspecific recommendation to use any 10-year risk calculator.
• Selective CAC scoring and one-time Lp(a) measurement are newly recommended for risk refinement.
• The strong primary-prevention statin threshold falls from 12% to 10% 10-year risk; consideration begins at about 5%.
• Moderate-intensity statins are newly suggested for adults with HIV, even at low calculated risk.
• Secondary prevention now includes statin-based choices and more intensive combination therapy for very-high-risk ASCVD.
• New nonstatin options are specified for complete statin intolerance, including bempedoic acid.
• Previous fixed limits on reassessment and lipid monitoring are removed; no specific interval is endorsed.

Source: Arnold MJ, et al. (2026 Sep 14) Ann Intern Med. A synopsis of the 2025 VA/DoD Clinical Practice Guideline for Lipid Management for Cardiovascular Disease Risk Reduction