Breast Density Masking and the Need for Precision Screening

# Breast Density Masking and the Need for Precision Screening *Published: 2026 Apr 28* Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. Marston NA(1), Bohula EA(1), Bhatia AK(2), De Ferrari GM(3), Leiter LA(4), Nicolau JC(5), Park JG(1), Murphy SA(1), Walsh E(2), Liu L(2), Verma S(6), Sattar N(7), Nicholls SJ(8), Lopez-Sendon J(9), Gouni-Berthold I(10), Tokgozoglu L(11), Blankstein R(12), Cyrille M(2), da Silva Lima GP(2), Giugliano RP(1), Sabatine MS(1); VESALIUS-CV Investigators. Collaborators: Lorenzatti AJ, Litvak Bruno MR, Mackinnon I, Alaguibe ED, Giunta G, Romano Montana O, Vogel D, Sala J, Besada DA, Romero Zarante A, Vico M, Smith Casabella TE, Gonzalez Colaso PDC, Montenegro E, Zaidman C, de Salvo MC, Perna E, Majul CR, Garcia Duran RO, Hominal M, Hermida S, Chacon C, Serrano AP, Albisu Di Gennaro JP, Stoermann WR, Mansilla MV, Koretzky M, Novaretto L, Schiavi L, Orlandini AD, Botto FO, Gelersztein E, Blumberg E, Nicholls S, Amerena J, Abhayaratna W, Roberts-Thomson P, Worthley M, Judkins C, Bisshop F, Begg A, Colquhoun D, Kostner K, Arya K, Cross D, Conradie A, Morton J, Purnell P, Hamilton A, Van Gaal W, Safaa A, Eccleston D, Ebenbichler C, Fasching P, Hanusch U, Ludvik B, Holzinger L, Saely C, Krychtiuk K, Kautzky-Willer A, Stulnig T, Sinnaeve P, Carlier S, De Meulemeester M, Wollaert B, Peeters A, Scott B, Vanduynhoven P, Verwerft J, Sarens T, Tavares Russo LA, Echeverria Sampaio CR, Giraldez R, Pimentel Filho P, Cunha Borges JL, Nasser Hissa M, Ribas Fortes JA, Cerci RJ, Nigro Maia L, Kormann AP, Arantes F, Reis G, Saraiva JF, Bertolim Precoma D, Ferreira Rossi PR, Giorgeto FE, Pereira A, Bodanese LC, Vidotti MH, Barreto da Silva RA, Cvetkov K, Todorov G, Gelev V, Vasilev I, Benov H, Goudev A, Postadzhiyan A, Koundurdjiev A, Penchev K, Zhelev V, Tokmakova M, Milanova M, Tisheva-Gospodinova S, Mincheva V, Tzekova M, Dimov B, Hristova-Tselova K, Dotcheva E, Kichukov K, Schlosser R, Mazer D, Constance C, Bajaj H, Baass A, Burstein J, Beca S, Henein S, Tsoukas G, Bergeron J, Gaudet D, Hartleib M, Heffernan M, Cha J, Peterson S, Tailor C, Alasaad H, Bata I, Vallieres G, Bourgeois R, OKeefe D, Ajala B, Woo V, Yung D, Khandwala H, Manyari D, Gupta M, Lonn E, Udell J, Khaykin Y, Frana P, Zemek S, Sknouril L, Schee A, Pazdera L, Koleckar P, Zidkova E, Bujdak J, Kvasnicka J, Blaha V, Urbanek R, Reichert P, Podpera I, Dulicek P, Machkova M, Fiserova N, Brtnikova S, Pozdisek Z, Cepelak M, Cech V, Homza M, Skrobakova J, Elbl L, Kala P, Raclavska L, Vesely J, Sochor K, Kryza R, Bartaskova D, Krupicka J, Matuska J, Hron J, Pirchala M, Busak L, Kucera D, Zlatohlavek L, Houra M, Reznicek V, Brotanek J, Polasek R, Parenicova I, Francek L, Sepsi M, Vaclavik J, Kukla P, Kuchar L, Karen I, Miklik R, Kosek Z, Krarup NT, Kjaerulf Jensen H, Sogaard P, Bendix Salkvist Jorgensen T, Korsgaard Thomsen K, Rossing P, Bottcher M, Eldrup N, Kamil Thomsen E, Hoi Justesen A, Nielsen SR, Jepsen JM, Husoy B, Valter I, Rosenthal A, Viitas L, Paumets M, Nieminen S, Suomi J, Koski AM, Kuusisto J, Putaala J, Nyman K, Kervinen K, Rissanen T, Hukkanen J, Taurio J, Strandberg T, Montalescot G, Lemesle G, Boccara F, Ducrocq G, Sevestre MA, Farah B, Fourme T, Paillard F, Messas E, Barone Rochette G, Canville A, Elbaz M, Poustis P, Cayla G, Georges JL, Guebre Egziabher F, Chague F, Buzura V, Charriere S, Khanoyan P, Range G, Ferrari E, Cariou B, Roubille F, Beygui F, Caudmont S, Weigmann I, Schenkenberger I, Licka M, Marks M, Borucki K, Rieth AJ, Appel KF, Kassner U, Laufs U, Wilke A, Axthelm C, Schaper F, Bergmann M, Stach-Jablonski K, Simon J, Fischer M, Leggewie S, Taggeselle J, Cremer S, Gebauer K, Koenig W, Kahrmann G, Bosiljanoff P, Placke J, Kollum M, Winkelmann B, Tsioufis K, Patsilinakos S, Liamis G, Tziomalos K, Styliadis I, Ntaios G, Tsougos E, Protogerou A, Stamatelopoulos K, Giannakoulas G, Naka K, Karavidas A, Katsiki N, Milkas A, Mavrokefalou E, Filippatos T, Kiss R, Merkely B, Harangi M, Toth K, Ungi I, Tomcsanyi J, Csanadi Z, Aradi D, Mark L, Zimmermann Z, Papp A, Lupkovics G, Papp A, Benczur B, Hornyik A, Lakatos F, Mucsi J, Nagy L, Szakal I, Mohacsi A, Reiber I, Lippai J, Konyves L, Hajdu C, Hamar S, Sarman B, Szilagyi A, Danos P, Nagy GG, Barany T, Berhes I, Nagy AC, Merlini PA, Licciardello G, Baldassarre MPA, Berti S, Rinaldi E, Tocci G, De Rosa S, Palermo A, Galie N, Trevisan R, De Ferrari GM, Trabattoni D, Morozova I, Teterovska D, Erglis A, Veze I, Jasinkevica I, Badariene J, Venceviciene L, Slapikas R, Urbonas G, Dobilas V, Strazdiene D, Kupstyte-Kristapone N, Kavaliauskiene R, Morales Villegas E, Aguilera Almazan F, Ruiz Ruiz VE, Alcocer Gamba MA, Garcia Reza R, De Los Rios Ibarra M, Aksoy I, Kauer F, van de Wal R, Oude Ophuis A, Prins F, Hermans W, Janse F, Koudstaal S, Emans M, Hoogslag P, Bartels G, Wildbergh T, Meijs M, Ronner E, Westendorp I, Kleijn L, Dijkmans P, Pos L, Rasoul S, Schaap J, Asselman M, Feenema-Aardema M, Groutars R, Nierop P, Swart H, Badings E, van der Zee M, Remkes W, Herrman J, van Bergen P, Stroes E, Hartong S, Kooy A, Post J, van de Ree M, Bax W, Visseren F, Monajemi H, El Messaoudi S, Rambharose R, Van Bemmel T, Daemen-Gubbels C, Alhakim M, Rensing B, Dekkers R, Adiyaman A, Paradies V, Bemelmans R, Hoek B, Verkleij R, Bednarkiewicz Z, Spyra J, Tomaszewski M, Zabowka M, Telec W, Pijanowski Z, Kafara M, Piepiorka M, Kopaczewski J, Grzegorzewski B, Kania G, Wojnowski L, Budaj A, Wozniak I, Kieltucki J, Czochra W, Pawlowicz L, Wlodarczak A, Dulak E, Staneta P, Bednarski J, Busz-Papiez B, Wozakowska-Kaplon B, Rozpondek P, Broncel M, Czerski T, Zabojszcz M, Cieslik K, Glowka R, Saminski K, Skorski M, Surman D, Niegowska J, Napora P, Karas P, Mirek-Bryniarska E, Artyszuk L, Tomaszewska-Kiecana M, Biegajlo J, Banach M, Skonieczny G, Loster M, Chlebus K, Jazwinska-Tarnawska E, Zurakowski A, Drelich G, Dudek D, Klecha A, Deres A, Dabrowska M, Cygler J, Aguiar C, Matos P, Pereira H, Monteiro P, Gavina C, Azevedo P, Vieira M, Ferreira R, Azevedo O, Stanciulescu GE, Militaru C, Vinereanu D, Podoleanu CG, Spiridon MR, Cosma D, Pintilei E, Crisan C, Andrei LD, Averkov O, Radchenko E, Argunova Y, Berns S, Bykov A, Voevoda M, Gordeev I, Dronov D, Veselovskaya N, Duplyakov D, Ezhov M, Zrazhevskiy K, Zykov M, Kobalava Z, Koziolova N, Kosmacheva E, Kostenko V, Kulibaba E, Lozhkina N, Lukyanov Y, Makukhin V, Meshkov A, Milyagin V, Nosov V, Osipova I, Pavlysh E, Pimenov L, Ryabov V, Semenova I, Smolenskaya O, Solovev O, Sorokin M, Statsenko M, Treshkur T, Shalaev S, Petrik E, Shvarts Y, Popov V, Shutemova E, Mordovin V, Morozov E, Sardinov R, Sherenkov A, Sveklina T, Pella D, Fulop P, Antalik L, Semetko J, Majercak I, Nociar J, Smik R, Dzupina A, Vinanska D, Banik M, Klabnik A, Oriesek R, Soosova I, Uhliar R, Lukacova J, Sosovec D, Lacka J, Skripova D, Urgeova L, Park KW, Jang YW, Yang TH, Kim BJ, Nam CW, Hong SJ, Park JS, Hong BK, Sim DS, Kim W, Choi YS, Lee CW, Kim BK, Cho MC, Hahn JY, Ahn S, Choi SY, Chae IH, Suarez Fernandez C, Ibarretxe Gerediaga D, Jarauta Simon E, Lopez Miranda J, Blanco Echevarria A, Tinahones Madueño FJ, Alonso Pedrol N, Brotons Cuixart C, Merino Torres JF, Arenillas Lara JF, Vazquez Ronda MA, Ortega Martinez de Victoria E, Hidalgo Urbano RJ, Iñiguez Romo A, Gonzalez Juanatey JR, Civera Andres M, Rodriguez Rodriguez V, Dalmau Gonzalez-Gallarza R, Peteiro Vazquez J, Modesto Dos Santos JL, Martin Armas JA, Gonzalez Bustos P, Pascual Figal DA, Mooe T, Lindholm CJ, Drakesby A, Soderberg S, Odenstedt J, Olsson A, Peterson M, Koskinen P, Salmonsson S, Sakne R, Bjorklund P, Lin TH, Huang CC, Lee IT, Wang JH, Yeh HI, Wang YC, Li YH, Hsieh IC, Wu CJ, Huang CN, Tseluyko V, Stets R, Stanislavchuk M, Rudenko L, Rishko M, Popova A, Prokhorov O, Parkhomenko O, Melashchenko I, Mishchenko L, Lymar Y, Korzh O, Karpenko O, Vakaliuk I, Alieksieieva L, Mitchenko O, McNally D, D Costa R, McCormack T, Beltran-Martinez A, Connolly D, Narayanan D, Felmeden D, Bain S, Lynch M, Paul N, Burkimsher R, Webster J, Donnelly P, Saravanan P, Shaw L, Issa B, Hossain R, Rajani R, Bickerton A, Negahban A, Moore P, Fairhead S, Heer A, Davies S, Wilson P, Jackson A, Ganeshkumar S, Irvine G, Poterajlo A, Krawczyk B, Walukiewicz P, Asubiaro J, Adesanya M, Dinu I, Nair D, Aslam S, Lillestol M, Abdelshaheed S, Shammas N, Khan T, Portnay E, Singh N, Brodie S, Wahid F, Santos V, Knickelbine T, Shapiro M, Revana M, Wilson V, Desai V, Hearne S, Hershon K, Lepor N, Ziajka P, Fritz R, Mondal P, Wiseman A, Nayda J, Grossman C, Lupovitch S, Forgosh L, Grubb S, Khurana S, Gangi S, Nicol P, Smith W, Patel M, Boccalandro F, Hilty K, Gabler S, Sotolongo C, Bergmark B, Jordan R, Strader JR, Donahoe S, Lamba S, P Benziger C, Arif A, Eid W, Nakhle S, Akhter F, Reddy J, Pomeroy W, Dokun A, Cohen R, Purdy D, Purnell J, Prashad R, Angiolillo D, Hafran M, DeAndrade K, Aspry K, Bajaj A, Miller R, Sloan L, Dharma C, Connelly T, Haught W, Kantaros L, Durrence H, Lieber I, Budoff M, El Shahawy M, Travers C, Potu R, Tannenbaum M, Dauber I, Subramanian S, Nadar V, Traboulssi M, Cox J, Kereiakes D, Carter L, Shah A, Onyema D, Farhat N, Schnitzler R, Humiston D, Garcia-Touza M, Aiyer A, Koren M, Arab D, Voss M, Vora S, Perez J, Mayfield R, Karlsberg R, East C, Iteld B, Fialkow J, Teklinski A, Bernstein M, Malhotra V, Lake L, Austin B, Platt G, Cavender M, Pant N, Hansen J, McNeill R, Chhabra A, Jaffrani N, Jones D, Akyea-Djamson A, Concha M, Wali A, Gianos E, Desouza C, Bassett Shaftoe L, Tan A, Zubairu J, Eaves W, Auerbach E, Connery L, Jardula M, Kandath D, Lerman S, Teufel E, Benjamin S, Bajaj S, Arambasick J, Feldman A, Sigurdsson A, Gudmundsdottir I, Nicolau J, Verma S, Leiter L, Changsheng M, Spinar J, Viigimaa M, Gouni-Berthold I, Cornel JH, Ferreira J, Kim HS, Lopez-Sendon J, Charng MJ, Tokgozoglu L, Sattar N, Blankstein R, Saver J, Bonaca M, Diaz R, Roe M, Giugliano RP, Bohula EA, Sabatine MS. Author information: (1)TIMI Study Group, Heart and Vascular Institute, Brigham and Women's Hospital, Boston, Massachusetts. (2)Amgen Inc, Thousand Oaks, California. (3)Cardiology Division, Department of Medical Sciences, University of Torino and Città della Salute e della Scienza, Torino, Italy. (4)Division of Endocrinology and Metabolism, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. (5)Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. (6)Division of Cardiac Surgery, St Michael's Hospital-Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. (7)School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom. (8)Victorian Heart Institute, Monash University, Melbourne, Victoria, Australia. (9)Idipaz Research Institute, Hospital Universitario La Paz, UAM, Madrid, Spain. (10)Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany. (11)Department of Cardiology, Hacettepe University, Ankara, Turkiye. (12)Heart and Vascular Institute, Brigham and Women's Hospital, Boston, Massachusetts. Comment in JAMA. 2026 Apr 28;335(16):1391-1392. doi: 10.1001/jama.2026.2392. ## IMPORTANCE Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis. ## OBJECTIVE To investigate whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without known significant atherosclerosis. DESIGN, SETTING, AND PARTICIPANTS VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab conducted across 774 sites in 33 countries and enrolling 12 257 patients with no prior myocardial infarction or stroke, LDL-C level 90 mg/dL or greater, and qualifying atherosclerosis or high-risk diabetes. This prespecified subgroup analysis examined outcomes in patients without known significant atherosclerosis (none of the following: prior arterial revascularization, arterial stenosis ≥50%, or coronary artery calcium score ≥100 Agatston units), all of whom had diabetes. Enrollment started in June 2019 and the last patient visit was July 2025, with a median follow-up of 4.8 years. INTERVENTION: Patients were randomized in a 1:1 ratio to subcutaneous administration of either evolocumab (140 mg every 2 weeks) or matching placebo added to optimally tolerated statin therapy. MAIN OUTCOMES AND MEASURES The dual primary end points were composites of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Secondary end points included all-cause mortality. ## RESULTS This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group (P < .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]). CONCLUSIONS AND RELEVANCE In high-risk patients without known significant atherosclerosis and with diabetes, evolocumab reduced the risk of a first major cardiovascular event. ## TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03872401. DOI: 10.1001/jama.2026.3277 PMCID: PMC13033171 DOI: 10.1001/jama.2026.2443