Expanding the Toolkit: Non-Statin Therapies, Broader Populations, and Closing the Treatment Gap

For the first time, the 2026 ACC/AHA guideline provides strong, evidence-based recommendations for patients who cannot tolerate statins—a group historically underserved by prior guidance. Outcome data now support bempedoic acid (from the CLEAR trial), PCSK9 monoclonal antibodies, ezetimibe, and inclisiran as viable alternatives. Rather than defaulting to high-intensity statin doses, clinicians can consider combination strategies such as a moderate-intensity statin paired with ezetimibe—a pairing shown in the RACING trial to match the cardiovascular event reduction of high-intensity monotherapy while improving tolerability and LDL goal achievement. The "rule of sixes"—where doubling a statin dose yields only an additional 6% LDL reduction versus 18% from adding ezetimibe—further reinforces early combination thinking.

The guideline is also clear that cardiovascular risk management should begin well before traditional thresholds. Patients with diabetes, chronic kidney disease (stage 3-4), and HIV all carry Class I recommendations for statin therapy regardless of PREVENT score. Cholesterol screening is now recommended in children aged 9 to 11, with earlier screening for children of affected parents. A one-time lipoprotein(a) measurement is recommended for all adults, given its role as an independent risk enhancer not captured in standard lipid panels.

Despite these advances, a substantial implementation gap persists. Data from the GOLD registry show that in the US, two-thirds of ASCVD patients have LDL levels above 70 mg/dL, and only 17% had their therapy intensified over 2 years. Closing this gap will require team-based care models—incorporating pharmacists, nurses, and prior authorization specialists—alongside EHR-embedded prompts and patient education. Goals, now that they are back, give both clinicians and patients a concrete number to work toward.