Advancing Lipid Management: Saudi Heart Association Position Statement on PCSK9-targeted Therapies in the Primary and Secondary Prevention of Cardiovascular Disease

Background Despite robust evidence for low-density lipoprotein cholesterol (LDL-C) reduction in atherosclerotic cardiovascular disease (ASCVD) prevention, attainment of guideline-recommended targets remains suboptimal in Saudi Arabia, especially among high- and very high-risk patients. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)-targeted therapies, which include monoclonal antibodies (evolocumab, alirocumab) and small interfering RNA (inclisiran), offer potent LDL-C lowering that can help address this gap. Methods The Saudi Heart Association (SHA) convened a multidisciplinary panel to review evidence from randomized controlled trials, real-world studies, and economic analyses on PCSK9-targeted therapies. Recommendations were developed through expert consensus, contextualized to the Saudi healthcare environment. Results and conclusions PCSK9 inhibitors (evolocumab, alirocumab) lower LDL-C substantially by around 60% and reduce the risk of adverse cardiovascular outcomes when added to maximally tolerated statins. Inclisiran achieves similar LDL-C reductions with biannual dosing, potentially improving adherence, though cardiovascular outcome data are pending. Both drug classes are well tolerated across diverse patient populations, including those with high or very high-risk, familial hypercholesterolemia (FH), recent acute coronary syndrome (ACS), or statin intolerance. The SHA expert panel recommends the early integration of upfront combination treatment including PCSK9-targeted therapies for patients with high risk features unlikely to reach LDL-C goals with statins ± ezetimibe, including recent ACS, FH, established ASCVD, metabolic conditions with end-organ damage, and statin intolerance. For Saudi populations, targeted integration of these agents into combination regimens offers a significant opportunity to close LDL-C treatment gaps and reduce residual ASCVD risk.