Bile acid sequestrants (resins) — specifically colesevelam, cholestyramine, and colestipol — are the lipid-lowering agents contraindicated in severe hypertriglyceridemia because they can significantly raise TG levels. This is a well-established class effect: by interrupting enterohepatic bile acid recirculation, resins upregulate hepatic VLDL synthesis, worsening hypertriglyceridemia. They are generally contraindicated when TG ≥300–400 mg/dL and absolutely avoided when TG ≥500 mg/dL.
This is distinct from other lipid-lowering agents with TG-raising nuances worth knowing:
Omega-3 acid ethyl esters (DHA + EPA combination, e.g., Lovaza) — can modestly raise LDL-C (though not apoB) in the setting of severe hypertriglyceridemia; this is not seen with icosapent ethyl (EPA-only).
Fibrates — have blunted to no TG reduction in familial chylomicronemia syndrome (FCS) due to absent lipoprotein lipase activity, so they do not raise TG per se but are ineffective in that specific context.
Niacin — actually lowers TG but is a last-line agent in severe hypertriglyceridemia given poor tolerability, hepatotoxicity, and worsening of insulin resistance.

The 2026 ACC/AHA Guideline on the Management of Dyslipidemia confirms that first-line agents for severe hypertriglyceridemia (≥500 mg/dL) are fibrates and prescription omega-3 fatty acids, and that bile acid sequestrants should be avoided in this context.