If a statin isn't enough, isn't tolerated, or you'd rather go lower without a bigger statin dose, two oral add-ons do real work — and, importantly, both now have hard-outcome trials behind them, not just LDL numbers.
Ezetimibe blocks cholesterol absorption in the gut, cutting LDL a further ~15–20% on top of a statin. IMPROVE-IT proved that adding it reduced events — the trial that validated the principle that lowering LDL helps regardless of the mechanism used. It's cheap, generic, and very well tolerated: the obvious first step when a statin alone falls short. Evidence ●●●●○
Bempedoic acid works one step upstream of statins and is activated only in the liver — so muscle tissue never takes it up, making it an option for people who can't tolerate statins. It lowers LDL ~20–25% alone (more with ezetimibe), and CLEAR Outcomes proved it reduced cardiovascular events in statin-intolerant patients. The main watch-outs are a small rise in uric acid and gout risk. Evidence ●●●●○
'Lower is better' — however you get there
IMPROVE-IT and CLEAR Outcomes extended the LDL-benefit principle beyond statins: what matters is getting ApoB/LDL down and keeping it down, not which drug does it. That's what makes combination therapy at lower doses a legitimate strategy.
The Cholesterol Guide