Oral PCSK9 inhibitors significantly reduced LDL-C and other atherogenic lipids in patients with hypercholesterolemia. A meta-analysis published in Circulation assessed lipid-lowering efficacy and safety across clinical trials in adults with elevated cholesterol. The pooled dataset included four randomized trials, comprising one Phase 1 and three Phase 2 trials, with a total of 1,114 participants. The primary outcome was percent change in LDL-C versus placebo, and the secondary outcomes included changes in Lp[a], ApoB, total cholesterol, triglycerides, and adverse events.

Oral PCSK9 inhibitors reduced LDL-C by a mean difference of –47.09% (95% confidence interval [CI], –53.22% to –40.96%; p < 0.001). MK-0616 achieved the largest LDL-C reduction (–53.69%; 95% CI, –61.05% to –46.34%), followed by NNC0385-0434 (–46.23%; 95% CI, –63.15% to –29.31%) and AZD0780 (–38.18%; 95% CI, –45.06% to –31.29%). Lp[a] decreased by 19.87%, ApoB by 37.70%, and total cholesterol by 24.29%.

Triglyceride reduction was not statistically significant (–3.58%; 95% CI, –7.63% to 0.47%; p = 0.08). Adverse-event rates were similar between groups (risk ratio [RR], 1.06; 95% CI, 0.95–1.17; p = 0.32).