Oral PCSK9 inhibitors as an emerging frontier in lipid management: A meta-analysis

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are effective lipid-lowering therapies that reduce cardiovascular risk in hypercholesterolemia. Recent advances include oral PCSK9i, which may offer advantages over injectables.

We aimed to assess the efficacy and safety of oral PCSK9i in reducing low-density lipoprotein cholesterol (LDL-C) levels, triglycerides, apolipoprotein B, and lipoprotein(a) compared with placebo on the background of standard medical therapy (SMT) in hypercholesterolemic populations.

This systematic review and meta-analysis included randomized controlled trials of oral PCSK9i vs placebo in patients with hypercholesterolemia at varying levels of atherosclerotic cardiovascular disease risk, and on stable lipid-lowering therapies. PubMed, Embase, and Cochrane were searched. Mean difference (MD) and odds ratio (OR) with 95% CI were pooled across trials for continuous and binary endpoints, respectively.

We included 3 randomized controlled trials, with 1020 patients, of whom 804 (78.9%) received oral PCSK9i. The average patient age was 61.6 years, and 55.2% were male. Mean percent changes from baseline of LDL-C levels (MD = -47.83%; 95% CI: -54.91, -40.74; P < .00001), triglycerides (MD = -11.65%; 95% CI: -15.44, -7.87; P < .0001), apolipoprotein B (MD = -38.71%; 95% CI: -45.48, -31.93; P < .00001), and lipoprotein(a) (MD = -19.80; 95% CI: -25.60, -14; P < .0001) were significantly reduced in patients treated with oral PCSK9i compared with placebo on the background of SMT. Serious adverse events were not increased with oral PCSK9i (OR = 0.74; 95% CI: 0.34, 1.62; P = .45).

Oral PCSK9i significantly reduced LDL-C, triglycerides, apolipoprotein B, and lipoprotein(a) without increasing serious adverse events. They show promise as effective, well-tolerated, and accessible lipid-lowering therapies for cardiovascular risk management.