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A retrospective propensity score-matched real-world cohort from Clalit Health Services (Israel, 2010–2023) compared PCSK9 mAbs with ezetimibe in adults without prior cancer using a 1-year latency. Over a median 4.6-year follow-up, overall cancer incidence was similar, while all-cause mortality was significantly lower with PCSK9 mAbs.",{"@graph":69,"@context":115},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/proprotein-convertase-subtilisinkexin-type-9-pcsk9-inhibition-and-cancer-risk-insights-from-a-large-propensity-matched-cohort-study/355667/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/proprotein-convertase-subtilisinkexin-type-9-pcsk9-inhibition-and-cancer-risk-insights-from-a-large-propensity-matched-cohort-study/355667.png","ImageObject",300,407,{"name":92,"@type":93},"Putri","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109],{"name":110,"@type":111,"acceptedAnswer":112},"How did PCSK9 mAb therapy affect mortality?","Question",{"text":113,"@type":114},"All-cause mortality was significantly lower in the PCSK9 mAb group (3% vs. 5%; HR 0.65; 95% CI, 0.54–0.80), and post-cancerdiagnosis mortality did not differ.","Answer","https://schema.org",{"og:url":83,"og:type":117,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":119,"canonical":83},"index,follow",{"doc_id":121,"site_id":62},355667,1790849324,{"code":4,"msg":5,"data":124},{"doc_id":121,"user_id":125,"nickname":92,"user_avatar":126,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":127,"file_id":128,"file_url":129,"file_type":130,"file_size":131,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":132,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":133,"faqs":134,"seo_title":135,"seo_description":67,"update_tm":136,"read_time":46},962085571259,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition and Cancer Risk: Insights from a Large Propensity-Matched Cohort Study  \nInbar Nardi Agmon 1,2,3,4,*  , Chen Gurevitz 1,2, Tzippy Shochat5, Shiri Kushnir5, Guy Witberg1,2, Amos Levi 1,2, Dan Gilon6, Ran Kornowski 1,2, Paaladinesh Thavendiranathan3, Husam Abdel Qadir3 and Zaza Iakobishvili7,8  \nProprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) lower LDL cholesterol and may influence cancer through immunomodulatory pathways. However, their effect on human cancer incidence remains unknown. We conducted a retrospective, propensity score-matched study (Clalit Health Services, Israel, 2010–2023) comparing PCSK9 mAbs to ezetimibe. Adults prescribed PCSK9 mAbs for 6 months or more were matched 1:3 toezetimibe-treated patients without prior cancer, applying a 1-year latency. The cohort included 9,876 patients (2,469 PCSK9 mAb; 7,407 ezetimibe; mean age 65) . During a median 4.6-year follow-up, cancer occurred in 12% of PCSK9 mAb users and 11% of ezetimibe users (HR 1.09 [95% CI, 0.95–1.25]) . In sex-stratified analysis, men on PCSK9 mAbs had a higher cancer incidence (12.5% vs. 10.3%, P = 0.03); no difference was observed in women. All-cause mortality was significantly lower in the PCSK9 mAb group (3% vs. 5%; HR 0.65 [95% CI, 0.54–0.80]) . Post-cancerdiagnosis mortality did not differ. In this large cohort, PCSK9 mAb therapy appeared safe regarding overall cancer risk and was associated with a significant reduction in all-cause mortality; the slightly higher cancer incidence in men may likely be attributed to a higher prevalence of baseline risk factors.  \nStudy Highlights  \nWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?  \n; Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) are potent low-density lipoprotein cholesterol (LDL-C) lowering agents. Preclinical studies suggest that PCSK9 may influence cancer biology by modulating tumor cell cholesterol metabolism and immune evasion mechanisms, specifically by downregulating major histocompatibility complex class I (MHC-I) expression on tumor cells. However, clinical evidence regarding the impact of long-term PCSK9 inhibition on human cancer incidence has been limited to post-hoc analyses of short-term randomized trials. WHAT QUESTION DID THIS STUDY ADDRESS?  \n; This study investigated whether long-term therapy with PCSK9 mAbs (evolocumab or alirocumab) is associated with an altered incidence of newly diagnosed malignancies compared to treatment with ezetimibe, an LDL-C lowering agent without known immunomodulatory effects, in a large, real-world cohort of patients without prior cancer.  \nWHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?  \n; In a propensity score-matched cohort of nearly 10,000 patients followed fora median of 4.6 years, PCSK9 mAb therapy  \nwas not associated with a significant difference in overall or site-specific cancer incidence compared to ezetimibe. Sexstratified analysis revealed a mildly higher cancer incidence in men, which likely reflects a higher baseline prevalence of shared cardiovascular and oncologic risk factors. Notably, PCSK9 mAb users experienced a significant 35% reduction in all-cause mortality, a benefit that was independent of concomitant statin use and likely driven by cardiovascular protection rather than anticancer activity.  \nHOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?  \n; These findings suggest that while PCSK9 mAbs provide a robust survival benefit, the subtle divergence in cancer incidence among men warrants continued long-term surveillance. The results reinforce the importance of intensive lipid management while suggesting that any hypothesized “protective” anticancer effects may be context-specific or require combination with other immunotherapies to manifest clinically.  \nReceived October 22, 2025; accepted January 28, 2026. doi:10.1002/cpt.70232  \nCLINICAL PHARMACOLOGY & THERAPEUTICS | VOLUME 119 ","cbCaipC0SAsQZBtO","https://ap.wps.com/l/cbCaipC0SAsQZBtO","pdf",450493,"English","# Study Highlights\n## Current knowledge on the topic\n## Question addressed by this study\n## Added value to knowledge\n## Clinical and translational implications","[{\"question\":\"How did PCSK9 mAb therapy affect mortality?\",\"answer\":\"All-cause mortality was significantly lower in the PCSK9 mAb group (3% vs. 5%; HR 0.65; 95% CI, 0.54–0.80), and post-cancerdiagnosis mortality did not differ.\"}]","Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition and Cancer Risk - Insights from a Large Propensity-Matched Cohort Study | PDF",1790120428]