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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #11 2026

Graphical abstract Dyslipidaemia

CV, cardiovascular; CVOT, CV outcome trials; LDL-C, low-density lipoprotein cholesterol; LDLR, low-density lipoprotein receptor; PCSK9, proprotein convertase
subtilisin/kexin type 9.

The results highlight the robust efficacy of injectable PCSK9 dependent LDL-C reductions of over 50% following a single
inhibitors. Fully human monoclonal antibodies, such as infusion, though long-term safety surveillance is still required.
evolocumab and alirocumab, have consistently demonstrated
a particularly significant LDL-C reduction of 40% to 70%, which While these therapies are highly effective and generally safe,
have translated into significant 15% relative risk reductions in lacking the muscle symptoms or hepatotoxicity associated with
major adverse CV events. statins, their real-world impact has been severely constrained

Newer injectable modalities have been developed to improve CLINICAL PEARLS FROM THE FACULTY
patient convenience. Lerodalcibep, an adnectin fusion protein,
achieves nearly 60% LDL-C reduction with smaller, room
temperature, stable monthly injections, while inclisiran, an siRNA
therapy, effectively silences hepatic PCSK9 synthesis to lower
LDL-C by roughly 50% with a highly convenient twice-yearly
dosing schedule.

Beyond injectables, there are highly promising results for
developing oral and gene editing therapies. Oral, small molecule
inhibitors like enlicitide and laroprovstat have successfully
demonstrated substantial placebo-adjusted LDL-C reductions
(ranging from 35% to 62% in trials) without the need for
injections. Furthermore, investigational clustered regularly WATCH
interspaced short palindromic repeats (CRISPR) base editing PROF. CHOONG HOU KOH DISCUSS
therapies, such as VERVE-102, aim to provide a permanent THE CLINICAL RELEVANCE OF THIS
functional cure by altering the PCSK9 gene directly in the liver. ARTICLE.
Early phase 1b trials have already shown highly durable, dose-

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