
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.




