Key Takeaways
- Oral PCSK9 inhibition is now a reality. With enlicitide approved and another oral agent in development, pharmacists can offer daily oral options to needle-averse or non-adherent patients who still need aggressive LDL lowering on top of statins.
- Universal Lp(a) screening is the new mandate. Because Lp(a) is genetically driven and unresponsive to lifestyle change, guidelines now call for testing every adult—identifying elevated patients now so they're ready for targeted therapy later.
- LDL/Lp(a) lowering does not yet equal proven event reduction. Pharmacists should temper expectations: Lp(a) agents show >95% reductions, but cardiovascular outcomes data confirming they prevent MI, stroke, or CV death remain years away.
In an interview with Pharmacy Times, Jeremy L. Johnson, PharmD, BCACP, CDCES, BC-ADM, professor of pharmacy practice at the Southwestern Oklahoma State University College of Pharmacy, discussed newly approved and emerging proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and the evolving role of lipoprotein(a) [Lp(a)] in cardiovascular risk. The discussion was based on a presentation he gave at the 2026 Association of Diabetes Care and Education Specialists (ADCES) Annual Meeting in Columbus, Ohio.
Johnson stressed that statins remain the gold standard for atherosclerotic cardiovascular disease risk reduction, with the newer agents serving as add-on therapy for patients who cannot reach increasingly strict low-density lipoprotein (LDL) targets. Among PCSK9 inhibitors, he noted that the monoclonal antibodies evolocumab (Repatha; Amgen) and alirocumab (Praluent; Regeneron) offer every-2-week dosing; lerodalcibep (Lerochol; LIB Therapeutics) offers a once-monthly injection (and a soon-to-be-available autoinjector device); and inclisiran (Leqvio; Novartis) is dosed just twice yearly after initial doses, each providing roughly 50% or greater LDL reduction. The most notable recent development, he said, is the arrival of oral PCSK9 inhibitors, led by enlicitide (Lipfendra; Merck & Co.), approved in July 2026, with another oral agent still under investigation.
Turning to Lp(a), Johnson explained that this independent, genetically determined risk factor now appears in the new American College of Cardiology/American Heart Association lipid guidelines, which recommend that every adult be screened. Because lifestyle changes have little effect on Lp(a), the immediate priority is identification, so patients are ready for targeted therapies once approved. He reviewed a robust pipeline—olpasiran, zerlasiran, lepodisiran, the oral agent muvalaplin, and pelacarsen—with several agents lowering Lp(a) by more than 95%. Importantly, Johnson cautioned that reducing the lipoprotein is only the first step: cardiovascular outcomes trials proving these agents actually prevent heart attacks, strokes, and cardiovascular death typically arrive years after approval, so their event-reduction benefit remains to be confirmed.
