biostudies-literatureUnknown331(9)Bakris GL<h4>Importance</h4>Angiotensinogen 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.<h4>Objective</h4>To evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens.<h4>Design, setting, and participants</h4>This 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 antihypertensivJAMA740-749https://www.ebi.ac.uk/biostudies/studies/S-EPMC10873804biostudies-literatureRNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial.PMC10873804Patton SFylenko YMcGill LMondoc NBailey GWest NQuenneville LMauri MMerrick ANovotny ECoreas DMcElheney MKendall TLeone STagsip MVillarreal SSantana CChalhoub FRamirez RCastello JBlanchard JRioux SViljoen MBlubaugh HRussell SArnold VCulbreth EHeredia GRioux JClowes JRafuse AVan Camp DWorthen IYu DWahaj ZAverett AKrambeck EVenereo JRadchenko OCortes-Maisonet GRamirez CTyler KShalala JVaquerano LCoslet JScatamacchia CAreeb Siddiqui MMishra PSikes KKundapati SNewsom-Henderson CAlbornoz Santofimio MPlantholt SRamsey JKarimjee NMcGrath VMarske CRamsey MSosa YWolfer JEsparza JDolfi KHarvalik PSanchez Crespo NMachado YLaurent JMir LSaunders JRuiz LRocco 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OBokhari FFaggett WLamontagne CYaniz MKornblatt AIsla ACleghorn MMister RNony TToor MValentine AAngel STeachman GChowdhry AMorin DMayfield RImran FBull LClayton CBakris GLFenuyi OButko OLachance PSheets LFilgueiras CRoman ABaron DHalliwell LJimenez AJimenez GMarmion CJimenez NJimenez LGonzales JPalmer JJimenez RJimenez STrudel JPlotka KPalmer KfalseRNA Interference With Zilebesiran for Mild to Moderate Hypertension: The KARDIA-1 Randomized Clinical Trial.<h4>Importance</h4>Angiotensinogen 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.<h4>Objective</h4>To evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens.<h4>Design, setting, and participants</h4>This 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 antihypertensiv2024-01-01T00:00:00Z2024 Mar2026-06-01T16:25:41.688Z2024-11-09T15:40:46.63ZS-EPMC108738043836357710.1001/jama.2024.0728