RNA Interference With Zilebesiran for Mild to Moderate Hypertension
Authors: Bakris George L. , Saxena Manish , Gupta Anil , Chalhoub Fadi , Lee Jongtae , Stiglitz Daniel , Makarova Nune , Goyal Nitender , Guo Weinong , Zappe Dion , Desai Akshay S. ,   KARDIA-1 Study Group, Carr George , Case Christopher , Jaeger Lauren , Bruns Lisa , Stratman Ginger , Kidwell Christy , Cunningham Suzin , Piccone Nicholas , Klein Mordecai , Acuna Maria , Arora Srishti , Clark Amanda , Fink Ezekiel , Garcia Cesia , George Astrid , Gray Elizabeth , Mahaffey Caroline , McElheney Maria , Ortiz Elizabeth , Saumya Sunny , Wallace Adele , Watts Jenelle , Zambrana Daisy , Denham Douglas , Rivera Erica , Avworo Ayoade , Hedges Parke , Fancher Corri , Abadier Rafik , Braud Lisa , Cenatiempo Laura , Elwood Amanda , Gray Linda , Gray Peter , Griffin Kimberly , Khan Hasibul , Kongquee Nadeen , LaTorraca Susan , Liles Tiffany , Livingston Jill , Lozano Marc , Lupton Amy , Lyles Tiffany , Mardini Deana , Moss Susan , Packer Karen , Patel Aakash , Russ Tina , Scinicariello Brianna , Trull Shannon , Warren Blair , Chalhoub Fadi , Angel Susan , Dhakhwa Sujeeta , Gabon Ivy , Goodwin Leticia , Joshi Jones Nandita , Joyce Mark , Kamble Niketa , McFall Brooke , Githiiyu Rose , Robinson Leticia , Tomlinson Lauren , Hadziavdic Emir , Vega Stephany , Greenwald James , Achan Jessica , Ruiz Lucille , Buksh Mehwish , Chauhan Omkar , Derisseau Elisee , Ferguson Faith , Grabowski Monika , Gumerova Larisa , Hernandez Miriam , Martin Kenna , Patel Krina , Nanda Dibnain , Perez Jose , Ribeca Corey , Rueda Elijah , Sordi Guth Ana , Zaki Nader , Green Ebony , Mondoc Nina , Buynak Robert , Andree Stephanie , Brazinsky Martha , Fuller Lisa , Green Nikki , Ibrahim Hannade , Idowu Marilyn , Lee Miranda , Lewis Erica , Luna Goldie , McNeal Rachel , Owens Alicia , Perez Consuelita , Petty Taryn , Smith Megan , Volom Patricia , Webb Angela , Williams Destiny , Yarosz Mark , Gabra Nashwa , Andrawis Nabil , Aziz Amy , Hanna Magda , Manalo Josefina , Helow Victoria , Davila William , Crisp Sydney , Douglas Yvonne , Everett Jenna , Graham Sarah , Heard Ellen , Mackie Michelle , Mayer Suman , Moore Lisa , Resurreccion Stephanie , Sidey Jennifer , Stephens Michael , Strickland Mary , Van Camp Dawn , Wilder Stephanie , Witt Anne , Wolfer Jolenne , Groben Lucas , Aeschliman Lindsey , Audlehelm Emily , Fitz Casey , Greene Judi , Hippen Emily , Johnson Michelle , Latcham Allan , Leggett Shekela , Link Keeta , Lovell James , Marlow Kourtney , Marske Cynthia , Maxwell Kelsey , Newsom-Henderson Charlotte , Oelberg Darcie , Ollinger Kathleen , Risius Rebecca , Ryther Kylea , Waddell Alyssa , Zellerman Tyler , Albornoz Santofimio Martin , Plantholt Stephen , Beatty Morgan , Blubaugh Heather , Bootz Tina , Cole Jeffrey , Conners Jasmine , Coombs Vicki , Goddard Chloe , Ince Carlos , Kiddy Gail , Klimuszka Barbara , Kuhn Frederick , Lowry David , Previll Patricia , Rioux Stephanie , Scott Jasmine , Shepherd Britney , Urffer Amy , Smiley Sarah , Lucksinger Gregg , Alvord Allison , Anderson Jordan , Block Courtney , Chan Ashley , Delgado John , Frost Kambrea , Gadbois Levi , Hamlin Danuel , Johnson Sarah , Juncal Vivianna , Kelly Kary , Kelly Emily , Kelly Lilly , Kerwin Avery , Kuehl Audrey , Ostovar Jaleh , Rackley Ryan , Rocha George , Sandberg Lacee , Sheghewi Sarah , Smith Tiffany , Taucher Ben , Vasquez Cecilia , Villa Rodriguez Francisca , Weisbart Jay , Wescom Veronica , Williams Keenan , Overcash Jeffrey Scott , Anorve Angela , Asmann Hunter , Bovee Gordon , Castillo Laura , Chu Hanh , Coslet Jordan , Davis Allison , Dinan Mary , Dubbula Amanda , Esparza Jacob , Foster Ann , Garcia Andrea , Gonzales Jessica , Gonzalez Lizette , Kappen Pat , Kornblatt Allison , Lauderdale Brandon , Lee Kia , Lindholm Sylvia , Lindsay Ashliegh , Llanos Gomez Luis , Marquez Adrienna , Meza Catherine , Odom Shandel , Orel Makenna , Paselio Shanna , Penziner Samuel , Pu Helen , Quillin Kimberly , Ramirez Cesar , Ramirez Roxanna , Salgado Monica , Shores Marcy , Taitingfong Raquel , Tande Jennifer , Tuiletufuga Van , Tyler Katrina , Vega Linda , Zepeda Karla , Anderson Corey , Carhill Nikki , Clark Benjamin , Dean Lisa , Devine Naomi , DiPeri Sophia , Espinal Gladys , Hawkins Ronald , Irra Gabriela , Ledezma Angela , Lopez-Wood Georgina , Luna Micaela , Mansour Wael , Marriott Tasha , Perez Ashley , Ramsey James , Reedy William , Spinks Hannah , Tanori Cecilia , Tatelbaum David , Vasquez Rudy , Vasquez Kim , Vigil Jori , Worthen Isabel , Yu Devin , Zuniga Jessica , Dennis Patrick , Alvarado Lauren , Cox Armand , Cullaro Victoria , Dunbar John , Giorlando Katherine , Hannan London , Hastings Tyler , Hoskins Geoff , Krambeck Emily , Laurent Juliana , Martinez Olga Michelle , Mister Reggie , Moss Autumn , Muli Margaret , Quinn Nicolette , Reed Brittany , Robinson Adam , Saavedra Casey , Simon Caitlin , Smith Derek , Touchet Dylan , Wright Annie , Trevino Miguel , DeVries Benjamin , Allison-Hicks Sara , Light Timothy , Rubach Wendy , Mai Kimberly , Osborn Tracey , Sheets Lori , Carver Dusty , Reichman Alan , Lotfi Djamchid , Berrios Nelson , Vulichi Sangeetha , Naguleswaran Tulashi , Subhan Yvonne , Rios Monica , Baron Diana , Khowaja Abdul , Nair Siddharth , Vicente Michael , Gonzalez Gomez Luvia Lizette , Acevedo Gomez Uriel Salvador , Lamichhane Janak , Ekomoda Efe , Nair Akhila , Maldonado Shana , Naqvi Mobina , Dayani Fahim , Patro Sontoshi , Golandaz LubnaGazal , Jaka Amin , Rios Santiago , Gurung Maushami , Gongloor Pratik , Coreas David , Demir Tarik , Celik Zehra , McGill Lora , Usdan Lisa , Arnold Valerie , Heckle Keerthi , Scatamacchia Carolyn , Anthony Codi , Marsh Carol , Fair Jernell , Stewart Anekeya , Hamlet Rebecca , Presley Robyn , Granberry Charles , Flowers Melissa , Houpt Cathy , O'Brien Debra , Evans Kelsey , Williams Mary , Sinatra Julia , Powell Irene , Flagg Tavia , Pipkin LaKeshia , Wheeler Vanessa , Wells Erin , Gruber Brandi , Jones Amber , Toor Monica , Iskiwitz Kelly , Boyd Mia , Epps Sharneiseca , Cole Frank , Grayson-Mathis Charlotte , Web Maci , Turner Catrina , Reese Krystal , Robinson Dana , Goodwin Atira , Parker Kyle , Ward Chantelle , Solomon Amber , Lawson Taylor , Pledger Marquita , Lane Peterson Amanda , Carignan Monique , Oguoma-Richards David , Jones Stacy , McFarland-Head Kiara , Bundeff Brittany , Wojtowicz Stephanie , Holland Cynthia , Sanders Taylor , Simon Lee , Lawrence Caitlin , Bolton Brittany , Lemoine Kandice , Harris Kasey , Kingsley Hilary , Bryant Danielle , Clawson Korie , Murphy Colleen , Crawford Allison Dale , Newman Gregory , Preece Dedra , Zook Pamela , Roznos Taylor , Russell Sharla , Rodriguez Richard , Roy Angela , Layle Stacey , Mehra Purvi , Bowen Samantha , Johnson Daniel , Guillen Natalie , Leone Sofia , McCormick Guinevere , Hermann Laurel , Sarno Lerner , Abellatif Taher , Cleghorn Monica , Elansary Aya , Israel Athalyah , Leeward Michelle , Parra Claudia , Harris Sydney , Patel Prianka , Cawley Megan , Castro Myrna , Miroshnikova Tatyana , Dever Michael , Venereo Jorge , Paez Henry , Isla Andres , Martin Yailin , Fernandez Ana , Hernandez Isabel , Isla Lavoy Andrew , Rios Nancy , Hernandez Armando , Denenberg Michael , McTier Treacy , Reynolds Caroline , Thomas Lacie , Eubanks Connie , Oliver Tori , Jacobs Michael , Mirkil Vincent , Menasche Kathleen , Yee Michael , Alvarado Vasquez Bonny , Garcia Candice , Elio Laura , Arenas Allan , Buena Clarissa , Garcia Cristina , Cannon Michael , Novotny Erin , Oliver Michelle , Cannon Amanda , Gatdula Mark , Gillenwater Cyn , Rafi Adam , Derian Wissam , Ramsey Miranda , Culbreth Evan , Fessler Catherine , Sorrill Kelly , Mauri Monica , Rosen Jeffrey , Acosta Olga , Brauchle Walter , Castaneda Dadllany , Castells Mailyn , Castro Daniela , Cespedes Laplace Maria Bibiana , Flerisme Magdala , Garcia Rocio , Gomez Julio , Hidalgo Michael , Jimenez Gabriela , Legon Miguel , Lella Victoria , Lemus Kimanys , Rico-Aramillo Sheilla , Rodriguez Maria , Rodriguez Yelida , Salazar Latisha , Santana Carlos , Tercero Nelly , Martin Earl E. , Acevedo Maria , Anderson Amy , Baig Talha , Baker Rana , Basrai Reemsha , Cabrera Nora , Caroll Cassidy , Chatmon Shanika , Cheema Sukhvinder , Chowdhry Anum , Cordero Nicole , Deandres Carolina , Deshpande Mounika , Dileep Ambily , Dolfi Kimberly , Eng Lara , Fountain Niccirria , Gali Ramani , Hernandez Adrienne , Iskandar Arsani , Khan Riaz , Knight Adrianna , Kundapati Soni , Lobo Irma , Lokhandwala Zahra , Lokhandwala Zara , Mahmood Faryal , Marediya Rifa , Martin Earl F , Melendez Mirella , Moosa Asfand , Motiwala Alefiyah , Muhebb Shamnun , Murray Monica , Rehman Muneeb , Rivera Ariel , Shah Ashay , Solorzano Sara , Somani Laila , Soneira Loreta , Starr Amy , Thompson Danielle , Torres Andrea , Tran Elizabeth , Ullah Mohammad Ali , Valentine Allie , Vaquerano Laura , Yake Amanda , Yousif Yousra , Zaldivar Ashley , Byars William , Brown Hillary , Claire Gaskin Anne , Clayton Caitlynn , Davis Christopher , Dillon Sydney , Driggers Belinda , Ferrell Anfernee , Green Danielle Elizabeth , Hunt Lisa , Jeffers Cathleen , Kirkland Cindy , Lopez Lina , Mayfield Ronald , Mercer Carole , Parsons Kathy , Patton Sharon , Puck Kayla , Restrepo Lina , Sheppard Tanya , Teachman Gina , Velez Jessica , Whitehead Amanda , Jain Mahendra , Asanji Gloria , Garrett Jennifer , Gill Katie , Hester DeAndrea , Jain Bela , Mitchell Yvette , Becker Teresa , McKeown-Biagas Cecilia , Fragoso Veronica , Holloway Lisa , Kowalski Tracy , Barr Shakira , Colville Bonnie , Yang Chen-Ho , Glasper Danitra , Phuah Allan , Miller Vicki , Schmidt Sheila , Jafri Ashraf , Sureshbabu Waheeda , Mir Leena , Sharma Stuti , Asaad Saja , Hasnain Muhammad , Ngo Tru , Hari Devi , Oheri Ikenna , Patwary Asma , Mohamed Mahmoud , Hernandez Priscilla , Gioia Jonatan , Dalal Abdeali , Ngban Pauline , Smith Sandra , Martinez Leal Bernardo , Assaf Akram , Martinez Alondra , Khan Khola , Castello Jacqueline , Potapenko Mariya , Wahaj Zurzar , Elmachtoub Faris , Akhtar Amna , Areeb Siddiqui Muhammad , Jamal Maira , Rizvi Mohammad , Sainz Karina , Lucky-Dania Sarah , Villarreal Stacy , Fernandez William , Hampton Shamarrian , Bellamy Jerry , Brown Lonisha , Doran Evan , Manzanares Eduardo , Palmer James , Sanders Aaron , Bokhari Faraya , Fenuyi Omowunmi , Greer Clarissia , Jang Hansol , Juanillo Andrea , Reese Crystal , Narla Dheeraj , Okoko Ijeoma , Woodham Cara , Eaton Rose , Khawaja Shariqa , Mushtag Tehreem , Nisar Bhutto Asifa , Solorsano Sara , Ahmed Sajeel , Shamim Rabia , Gonzalez Norma , Ardoin Felicia , Moore Joshua , Nuncio Nina , Ray Eric , Sikes Kara , Troutman Imani , West Natasha , Wilson Quiana , Young Nikisha , Baloch Misbah , Karimjee Najmuddin , Carroll Kristy , Broachwala Sakina , Calais Natalee , Laabs Jessica , Marler Karen , Rizvi Samana , Syed Amar , Syed Narjis , Rizvi Zamir , Hariwala Zohair , Gloyd Patty , Rizvi Abid , Marcum Benjamin , Carswell Joshua , Fanning Cortney , Bull Lesslie , Corta Peter , James Holly , Martinez David , Scurlark Robin , Elliott Stephanie , Beck Sydney , Beck Cayla , Glover Sarah , Bonson Jasmine , Patel Tanisha , Matthew Garrett , Davidoff Kyla , Vesely Jim , Horton Cyrus , Barbour Rebecca , Pereira Isabel , Rivero Gina , Alston Denise , Miller Paulina , Downing Frances , Sanchez Crespo Nelia , Schwartz Howard , Mederos Surisaday , Tamayo Janet Sentil , Shapiro Craig , Mallet Orbein , Plotka Karenda , Valladares Carlos , Palmer Karenda , Deltejo Dayana , Garcia Katherine , Camacho Marilein , Chanza Yarixa , Morera Jocelyn , Davis Claudette , Dawson Karlene , Rosales Vivian , Torres Dunia , Pinero Maria , Cruz Catherine , Rivera Beatriz , Balebona Patricia , Basurco Andrea , Montoya Jenny , Yaniz Mikael , Petit Phar Pedro , Filgueiras Christy , Fernandez May , Skrine Latauri , Alcantara Aaliarys , Parodis Isnier , Parodis Jessica , Jara Jailene , Alouption Joslandey , Yan Malvin , Padilla Jesse , Cruz Carolina , Bran Bianca , Flores Vanessa , Perez Leandro , Labovitz Arthur , Roth Tracey , Javier Julian , Jimenez Lorenzo , Ojeda Carmen , Caceres Maria , Misir Caren , Rudd Kyle , Ramos Juan , Deeb Wasim , Bisharat Mohannad , Dennis-Saltz Amy , Sutton David , Magee James , Ashchi Majdi , Goldfaden Rebecca , Sheikh-Ali Mae , Kelly Stacey , Nicolas Saikali Elias , Rodel Ramirez Gloria , Domingo Debbie , Hodge William , Greenewalt Adrienne , Stamschror Lauren , Preston Kaitlyn , Petschonek Leann , Graf Katie , Sutton Lynsey , Edson Meghan , Charron Madison , Taylor Mika , Knisely Emily , Gore Ashwini , Jones Thomas , Johns Barry , Sheldon Jennifer , Merritt Kayla , Hichkad Lisa , Barbee Leah , Riley Amanda , Alexander Lindsay , Dasher Lilly , Torres Lopez Elio Argimiro , Baez Bonilla Rafael , Loza Anibal , Hernandez Dunia , Perez Yaili , Perez Alejandro , Perez Yalily , Medina Denisse , Mantero Emilio , Vega Ramses , Pedraza Noel , Sosa Damian , Robles Lys , Machado Yennifer , Sosa Yoandra , Guzman David , Grio Maricor , Frias Juan , Kelly    Sharon , Leibowitz Mark , Nelson John , Handy  Cheryll  , Greenberg Alina , Vega Norma , Francisco Angelica , Soto   Coralia , Arcadia    Sinthia , Francisco Eulalia , Escareno Nicol , Ayala Nelly , Muniz Jennifer , Espino                                 Jose , Vargas Daniel , Jimenez Rosie , Lopez Stephanie , Gallaga Iliana  , Heredia  Genesis  , Barranco Santana Elizabeth , Mendoza-Rodriguez Rafael , Cancel Santana Sara , Román Alejandra , Arroyo Torres Irmaris , Franceschini Velma , Garcia Brenda , Jimenez Nancy , Irizarry Ortiz Michele , Torres Antommattei Armando , Comulada-Rivera Angel , Pintado Andrea , Ortiz Sonia , Rodriguez Adamaris , Mojica Ramirez Rosa , Olofintuyi Anthony , Alvarez Ricardo , Pitts Jay , Samraj Jackelyn , Vasbinder Alma , Averett Amaya , Kane Thomas , Farley Harlicia , Kendall Thomas , Kemmerlin Richard , Saunders Jackie , Livingston Yolanda , McLean Barry , Mayer Maureen , Goodwin Valerie , Ngugi Evelyne , Mishra Prateek , Carter Hannah , Szymela Lorie , Imran Ali , Abdallah Saiaf , Clarke Nadia , Hernandez Latog Sylvania , Moore  Broderick , Lopez Miguel , Tagsip Maureen , Nepali Prakash , Kumaran Nivi , Jacinto Greta , Magsino Catherine , Batalla Freddie , Imran Feroza , Montgomery Richard , Riggs Stephanie , Haamid Shavonna , Whitt Catherine , Hopper William , Smith Dominique , Kordsmeier Julia , Sherron Courtney , Plummer Miyah , Jimenez Sherisse , Newkirk Airelle , Murray Laura , Scott Haley , Whitney Rebecca , Castro Monica , Rhames Michelle , Cortes-Maisonet Gregorio , Miranda Martinez Luis , Allende-Vigo Myriam , Vila Karina , Santiago Rivera Michelle , Yunker Valerie , Rivera Bryan , Rodriguez Alex , Rivera Carla , Reyes Blanco Genesis , Batista Colon Keven , Cruz Mariely , Nweke Chinedu , Okafor Norah , Nweke Angela , Chaves-Montoya Daisy , Patrick Heather , Alvarez Stephanie , Momeh Eunice , Anaele Cyriacus , McArthur Katherine , Longonje Peter , Husbands Danielle , Williams Iasia , Dillingham Christine , Sanchez Sayyah Gloria , Carey Laura , Brock Clarissa , Hussain Rubaba , Sultana Khadiza , Mohammad Omar , Lopez Jennifer , Bittencourt Valeria , Prasad Sneha , Akther Nafsun , Smith Timothy , Rocco Sheri , Straatmann Donna , Stoneman Jill , Maryas Elizabeth , Gravier Johanna , Faggett Walter , Jimenez Andres , Maya Alvarez Maria , Evora Wendy , Herrera Alcira , Leonardi Lorena , Karns Adam , Sisneros Edith , Hong Sarom , Rudyk Iurii , Medentseva Olena , Alexeeva Maryna , Strakhova Nataliya , Lozyk Tetyana , Babichev Denys , Yushko Kostiantyn , Tseluyko Vira , Zhadan Andriy , Butko Olena , Mishchenko Oksana , Radchenko Olha , Karpenko Oleksandr , Klimko Polina , Berezhniak Anna , Todoriuk Liudmyla , Bezuglova Svitlana , Mitskevych Liubov , Kizim Svitlana , Nevolina Inna , Galchenko Oksana , Korzh Oleksii , Pankova Olena , Fylenko Yana , Ziabchenko Valeriia , Krasnokutskiy Sergiy , Liashok Artem , Donets Oleksandra , Mishustina Anna , Khrustalyova Liliya , Donets Dmytro , Rybachok Yuliia , Senchylo Vyacheslav , Lyakhova Iryna , Takhaieva Olena , Shkroba Anna , Shchypak Diana , Tryshchuk Nadiya , Pieshkova Olga , Karaia Olena , Yakovleva Anna , Horoshko Olha , Lohdanidi Tetiana , Belei Nestor , Kuzmenko Inga , Demchuk Tetiana , Cherniuk Sergii , Kozliuk Alina , Kovalenko Volodymyr , Adarichev Valerii , Vakaliuk Igor , Tymochko Nataliia , Sovtus Volodymyra , Haliuk Nadiia , Gaudet Daniel , Côté Fanny , Milot Jean-Philippe , Roy Nathalie , Larouche Andrea , Piché Johanne , Charest Laurie-Anne , Dufour Josiane , Pageau Joannie , Audet-Verreault Noemie , Côté Lyne , Gagnon Melissa , Côté Véronique , Morin Denise , Fortin-Mimeault Jessica , Brassard Marc-Olivier , Gagne Helene , Rousseau Sophie , Sia Ying Tung , Guzzetti Ezequiel , Alejandro Gisbert Ramon , Dias Mariana , de Oliveira Mariana , Cote Claudia , Rodrigues Izabel , Blanchard Johanne , Labbe Laurence , Dumoulin Lemay Sabrina , Beauchemin Kathleen , Turcotte Roxanne , Beaudoin Annabelle , Saliphod Chansamone , Lamontagne Chantal , Trudel Josiane , Beaudoin Carolyne , Blanchard Josée , Larouche Annie , Robinaud Cecile , Paré Valérie , Bergeron Alexandre , Bilodeau Maude , Bellavance Ethel , Betit Eve , Fortier Karine , Racine Josee , Perras Dinah , Boulanger Elyse , Beauchesne Christelle , Lehoux Sarah , Turgeon Vickie , Cote Rachele , Tardif Marie-Eve , Aggarwal Naresh , Aggarwal Puja , Patel Bharti , Dhaliwal Gurdeep , Aggarwal Preeti , Tellier Guy , Gagne Gilbert , Laperriere Luc , Shalala Jennifer , Danchuk Janelle , Barrette Catherine , Lauzon Lydia , Langille Natalie , Gagné Sarah , Lupien Joanie , Brochu Raphael , Coallier Sophie , Vaillancourt Catherine , Lachance Pierre , Carbonneau Diane , Thibault Helene , Bouchard Luc , St-Cyr Andreanne , Rioux Johanne , Quenneville Laureanne , Gagnon Constance , Nony Theana , Laberge Pascale , Corbin Annabelle , Patry Isabelle , Savage Sophie , MacNeil Melanie , Murdock Andrea , Inglis Jill , Libbus Katelyn , Smith Kathryn , Johnson Deseray , Walters-Findlay Linda , Harris Laura , Hutchison Taylor , Rafuse Autumn , Thorsen Julie , MacDonald Greg , Akhras Ronald , Assef Richard , Irani Elise , Khayat Rania , Guidolin Scott , Gupta Anil , Price David , Gandhi Amisha , Chhabra Ajay , Gandhi Bhavya , Acharya Shrey , Panchal Maheshwari , Kansal Bindu , Bailey Gordon , Harvalik Paula , Demchuk Kerri , Saxena Manish , Collier David , David Colvell , Quiros Benildo Jr , Patel Mital , Balawon Armida , Galera Francis , Michalska Ania , Piniera Brian , Uddin Rahat , Abbott Joanna , Faulkner Karen , Yousef Tamer , Love Kyle , Zagdanski Ariella , Slaney Susan , Anderson Michelle , Leath Aimee , Dunlop Cheryl , Hardy Elizabeth , Wall Shannon , El-Koubani Osman , Kelt Tracy , Connolly Billy-Jean , Marmion Cheryl , Alapati Maheswari , Simmons Louise , Colquhoun Caroline , Clyde Darren , Mooty Adrian , Mullen Nicole , Viljoen Marianne , Trevor Lucy , Pretswell Carol , Austin Catherine , Munthali Chigomezgo , Munsoor Imrozia , Venkate Gowda Madhu , Ozunlu Pembe , Keighley Peter , Jones Alison , James Annette , Pollitt Joanne , Littlewood Wendy , Al-Sheikhly Lena , Lee David , Nistor Denise , Roberts Elaine , Mawdsley Gayle , Sobolewska Kamila , Hannis Katrina , Wojtkiewicz Klaudia , Stopford Lauren , Halliwell Lindsay , Mort Veronica , McGrath Victoria , Osborne Harry , Merrick Alison , Basikolo Cathrine , Ghysels Inge , Fenlon Laura , Beech Lucy , Munoz Olga Lusquinos , Bilton Sarah , Goddard Lyne , Gillon Tracey , Taylor Stacy , Tyson Brianne , Connor Victoria , Felber Hannah , Fallows Angela , Clowes Jacqueline , Cheung Shirley 
Published: February 2024

ImportanceAngiotensinogen is the most upstream precursor of the renin–angiotensin–aldosterone system, a key pathway in blood pressure (BP) regulation. Zilebesiran, an investigational RNA interference therapeutic, targets hepatic angiotensinogen synthesis.ObjectiveTo evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens.Design, Setting, and ParticipantsThis phase 2, randomized, double-blind, dose-ranging study of zilebesiran vs placebo was performed at 78 sites across 4 countries. Screening initiation occurred in July 2021 and the last patient visit of the 6-month study occurred in June 2023. Adults with mild to moderate hypertension, defined as daytime mean ambulatory systolic BP (SBP) of 135 to 160 mm Hg following antihypertensive washout, were randomized.InterventionsRandomization to 1 of 4 subcutaneous zilebesiran regimens (150, 300, or 600 mg once every 6 months or 300 mg once every 3 months) or placebo (once every 3 months) for 6 months.Main Outcomes and MeasuresThe primary end point was between-group difference in least-squares mean (LSM) change from baseline to month 3 in 24-hour mean ambulatory SBP.ResultsOf 394 randomized patients, 377 (302 receiving zilebesiran and 75 receiving placebo) comprised the full analysis set (93 Black patients [24.7%]; 167 [44.3%] women; mean [SD] age, 57 [11] years). At 3 months, 24-hour mean ambulatory SBP changes from baseline were −7.3 mm Hg (95% CI, −10.3 to −4.4) with zilebesiran, 150 mg, once every 6 months; −10.0 mm Hg (95% CI, −12.0 to −7.9) with zilebesiran, 300 mg, once every 3 months or every 6 months; −8.9 mm Hg (95% CI, −11.9 to −6.0) with zilebesiran, 600 mg, once every 6 months; and 6.8 mm Hg (95% CI, 3.6-9.9) with placebo. LSM differences vs placebo in change from baseline to month 3 were −14.1 mm Hg (95% CI, −19.2 to −9.0; P &amp;lt; .001) with zilebesiran, 150 mg, once every 6 months; −16.7 mm Hg (95% CI, −21.2 to −12.3; P &amp;lt; .001) with zilebesiran, 300 mg, once every 3 months or every 6 months; and −15.7 mm Hg (95% CI, −20.8 to −10.6; P &amp;lt; .001) with zilebesiran, 600 mg, once every 6 months. Over 6 months, 60.9% of patients receiving zilebesiran had adverse events vs 50.7% patients receiving placebo and 3.6% had serious adverse events vs 6.7% receiving placebo. Nonserious drug-related adverse events occurred in 16.9% of zilebesiran-treated patients (principally injection site reactions and mild hyperkalemia) and 8.0% of placebo-treated patients.Conclusions and RelevanceIn adults with mild to moderate hypertension, treatment with zilebesiran across a range of doses at 3-month or 6-month intervals significantly reduced 24-hour mean ambulatory SBP at month 3.Trial RegistrationClinicalTrials.gov Identifier: NCT04936035