{"id":"https://openalex.org/W7225832108","doi":"https://doi.org/10.3390/jcm15228811","title":"Fourth-Line Treatment in Resistant Hypertension After QUADRO: Comparative Evidence, Single-Pill Strategies, and Clinical Selection","display_name":"Fourth-Line Treatment in Resistant Hypertension After QUADRO: Comparative Evidence, Single-Pill Strategies, and Clinical Selection","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225832108","doi":"https://doi.org/10.3390/jcm15228811"},"language":"en","primary_location":{"id":"doi:10.3390/jcm15228811","doi":"https://doi.org/10.3390/jcm15228811","is_oa":true,"landing_page_url":"https://doi.org/10.3390/jcm15228811","pdf_url":null,"source":{"id":"https://openalex.org/S2737969411","display_name":"Journal of Clinical Medicine","issn_l":"2077-0383","issn":["2077-0383"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","ki-jl-1","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Medicine","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/jcm15228811","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5063576727","display_name":"Daniel Miron Brie","orcid":"https://orcid.org/0000-0001-9003-456X","observed_orcids":["https://orcid.org/0000-0001-9003-456X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Daniel Miron Brie","raw_affiliation_strings":["Cardiovascular Disease Institute Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania","Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania"],"raw_orcid":"https://orcid.org/0000-0001-9003-456X","affiliations":[{"raw_affiliation_string":"Cardiovascular Disease Institute Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania","institution_ids":[]},{"raw_affiliation_string":"Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062827288","display_name":"Cristian Morno\u015f","orcid":"https://orcid.org/0000-0002-6096-9601","observed_orcids":["https://orcid.org/0000-0002-6096-9601"]},"institutions":[{"id":"https://openalex.org/I4210088791","display_name":"Victor Babe\u0219 University of Medicine and Pharmacy Timi\u0219oara","ror":"https://ror.org/00afdp487","country_code":"RO","type":"education","lineage":["https://openalex.org/I4210088791"]}],"countries":["RO"],"is_corresponding":false,"raw_author_name":"Cristian Morno\u0219","raw_affiliation_strings":["Cardiovascular Disease Institute Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania","Department of Cardiology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania","Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania"],"raw_orcid":"https://orcid.org/0000-0002-6096-9601","affiliations":[{"raw_affiliation_string":"Cardiovascular Disease Institute Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania","institution_ids":[]},{"raw_affiliation_string":"Department of Cardiology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania","institution_ids":["https://openalex.org/I4210088791"]},{"raw_affiliation_string":"Research Center of the Institute of Cardiovascular Diseases Timi\u0219oara, Gheorghe Adam Street, No. 13A, 300310 Timi\u0219oara, Romania","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066902442","display_name":"Roxana Popescu","orcid":"https://orcid.org/0000-0002-9387-1141","observed_orcids":["https://orcid.org/0000-0002-9387-1141"]},"institutions":[{"id":"https://openalex.org/I4210088791","display_name":"Victor Babe\u0219 University of Medicine and Pharmacy Timi\u0219oara","ror":"https://ror.org/00afdp487","country_code":"RO","type":"education","lineage":["https://openalex.org/I4210088791"]}],"countries":["RO"],"is_corresponding":false,"raw_author_name":"Roxana Popescu","raw_affiliation_strings":["ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","Department of Cell and Molecular Biology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania"],"raw_orcid":"https://orcid.org/0000-0002-9387-1141","affiliations":[{"raw_affiliation_string":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","institution_ids":["https://openalex.org/I4210088791"]},{"raw_affiliation_string":"Department of Cell and Molecular Biology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","institution_ids":["https://openalex.org/I4210088791"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5114595911","display_name":"Alina Didu\u021ba Brie","orcid":"https://orcid.org/0009-0002-4078-1537","observed_orcids":["https://orcid.org/0009-0002-4078-1537"]},"institutions":[{"id":"https://openalex.org/I4210088791","display_name":"Victor Babe\u0219 University of Medicine and Pharmacy Timi\u0219oara","ror":"https://ror.org/00afdp487","country_code":"RO","type":"education","lineage":["https://openalex.org/I4210088791"]}],"countries":["RO"],"is_corresponding":false,"raw_author_name":"Alina Didu\u021ba Brie","raw_affiliation_strings":["ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","Department of Cell and Molecular Biology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","\u201cLouis \u021aurcanu\u201d Emergency Children Hospital, Doctor Iosif Nemoianu Street, No. 2, 300011 Timi\u0219oara, Romania"],"raw_orcid":"https://orcid.org/0009-0002-4078-1537","affiliations":[{"raw_affiliation_string":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","institution_ids":["https://openalex.org/I4210088791"]},{"raw_affiliation_string":"Department of Cell and Molecular Biology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Tudor Vladimirescu Street, No. 14, 300174 Timi\u0219oara, Romania","institution_ids":["https://openalex.org/I4210088791"]},{"raw_affiliation_string":"\u201cLouis \u021aurcanu\u201d Emergency Children Hospital, Doctor Iosif Nemoianu Street, No. 2, 300011 Timi\u0219oara, Romania","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5063576727"],"corresponding_institution_ids":[],"apc_list":{"value":2600,"currency":"CHF","value_usd":3137},"apc_paid":{"value":2600,"currency":"CHF","value_usd":3137},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"15","issue":"22","first_page":"8811","last_page":"8811"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10144","display_name":"Blood Pressure and Hypertension Studies","score":0.9955999851226807,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10144","display_name":"Blood Pressure and Hypertension Studies","score":0.9955999851226807,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11839","display_name":"Hormonal Regulation and Hypertension","score":0.0032999999821186066,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12664","display_name":"Clinical practice guidelines implementation","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.973800003528595},{"id":"https://openalex.org/C2776379505","wikidata":"https://www.wikidata.org/wiki/Q422188","display_name":"Spironolactone","level":3,"score":0.9602000117301941},{"id":"https://openalex.org/C84393581","wikidata":"https://www.wikidata.org/wiki/Q82642","display_name":"Blood pressure","level":2,"score":0.6001999974250793},{"id":"https://openalex.org/C3019558611","wikidata":"https://www.wikidata.org/wiki/Q41861","display_name":"Resistant hypertension","level":3,"score":0.5856999754905701},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.47209998965263367},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.4702000021934509},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4699999988079071},{"id":"https://openalex.org/C27081682","wikidata":"https://www.wikidata.org/wiki/Q269829","display_name":"Placebo","level":3,"score":0.45239999890327454},{"id":"https://openalex.org/C177713679","wikidata":"https://www.wikidata.org/wiki/Q679690","display_name":"Intensive care medicine","level":1,"score":0.4318999946117401},{"id":"https://openalex.org/C2778198053","wikidata":"https://www.wikidata.org/wiki/Q181754","display_name":"Heart failure","level":2,"score":0.41510000824928284},{"id":"https://openalex.org/C164705383","wikidata":"https://www.wikidata.org/wiki/Q10379","display_name":"Cardiology","level":1,"score":0.40299999713897705},{"id":"https://openalex.org/C57900726","wikidata":"https://www.wikidata.org/wiki/Q492905","display_name":"Diastole","level":3,"score":0.3483999967575073},{"id":"https://openalex.org/C168563851","wikidata":"https://www.wikidata.org/wiki/Q1436668","display_name":"Randomized controlled trial","level":2,"score":0.33880001306533813},{"id":"https://openalex.org/C126894567","wikidata":"https://www.wikidata.org/wiki/Q105650","display_name":"Urology","level":1,"score":0.31349998712539673},{"id":"https://openalex.org/C2779473830","wikidata":"https://www.wikidata.org/wiki/Q1540899","display_name":"MEDLINE","level":2,"score":0.28760001063346863},{"id":"https://openalex.org/C81917197","wikidata":"https://www.wikidata.org/wiki/Q628760","display_name":"Selection (genetic algorithm)","level":2,"score":0.28189998865127563},{"id":"https://openalex.org/C2781203188","wikidata":"https://www.wikidata.org/wiki/Q1676817","display_name":"Microalbuminuria","level":3,"score":0.26350000500679016},{"id":"https://openalex.org/C95190672","wikidata":"https://www.wikidata.org/wiki/Q815382","display_name":"Meta-analysis","level":2,"score":0.2587999999523163},{"id":"https://openalex.org/C2777097880","wikidata":"https://www.wikidata.org/wiki/Q988405","display_name":"Essential hypertension","level":3,"score":0.25110000371932983},{"id":"https://openalex.org/C159641895","wikidata":"https://www.wikidata.org/wiki/Q108377937","display_name":"Renal function","level":2,"score":0.2506999969482422}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3390/jcm15228811","doi":"https://doi.org/10.3390/jcm15228811","is_oa":true,"landing_page_url":"https://doi.org/10.3390/jcm15228811","pdf_url":null,"source":{"id":"https://openalex.org/S2737969411","display_name":"Journal of Clinical Medicine","issn_l":"2077-0383","issn":["2077-0383"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","ki-jl-1","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Medicine","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3390/jcm15228811","doi":"https://doi.org/10.3390/jcm15228811","is_oa":true,"landing_page_url":"https://doi.org/10.3390/jcm15228811","pdf_url":null,"source":{"id":"https://openalex.org/S2737969411","display_name":"Journal of Clinical Medicine","issn_l":"2077-0383","issn":["2077-0383"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","ki-jl-1","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Medicine","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":107,"referenced_works":["https://openalex.org/W953421312","https://openalex.org/W1544563963","https://openalex.org/W1592471891","https://openalex.org/W1797367453","https://openalex.org/W1970957826","https://openalex.org/W1973686627","https://openalex.org/W1977186839","https://openalex.org/W1977607782","https://openalex.org/W1980094514","https://openalex.org/W1980533403","https://openalex.org/W1996348084","https://openalex.org/W2003145631","https://openalex.org/W2028147850","https://openalex.org/W2043244508","https://openalex.org/W2063753451","https://openalex.org/W2064377767","https://openalex.org/W2064532153","https://openalex.org/W2089259727","https://openalex.org/W2093767567","https://openalex.org/W2103256591","https://openalex.org/W2103881469","https://openalex.org/W2110020527","https://openalex.org/W2111844910","https://openalex.org/W2111945961","https://openalex.org/W2113750355","https://openalex.org/W2114075168","https://openalex.org/W2114333967","https://openalex.org/W2118344567","https://openalex.org/W2118958399","https://openalex.org/W2125226019","https://openalex.org/W2129950671","https://openalex.org/W2129991662","https://openalex.org/W2133667581","https://openalex.org/W2140615065","https://openalex.org/W2142937102","https://openalex.org/W2145989311","https://openalex.org/W2148827677","https://openalex.org/W2150734413","https://openalex.org/W2151009383","https://openalex.org/W2156249907","https://openalex.org/W2157677292","https://openalex.org/W2159854507","https://openalex.org/W2160547085","https://openalex.org/W2172086404","https://openalex.org/W2290633895","https://openalex.org/W2296998040","https://openalex.org/W2305118939","https://openalex.org/W2323458614","https://openalex.org/W2378917168","https://openalex.org/W2435193784","https://openalex.org/W2565616619","https://openalex.org/W2605241743","https://openalex.org/W2608505166","https://openalex.org/W2610569314","https://openalex.org/W2742167604","https://openalex.org/W2753813400","https://openalex.org/W2767799851","https://openalex.org/W2796868581","https://openalex.org/W2800891490","https://openalex.org/W2811123125","https://openalex.org/W2885869386","https://openalex.org/W2887966018","https://openalex.org/W2896865390","https://openalex.org/W2904823586","https://openalex.org/W2910511370","https://openalex.org/W2922577842","https://openalex.org/W2943413777","https://openalex.org/W2972966903","https://openalex.org/W2991065707","https://openalex.org/W3041745066","https://openalex.org/W3093851112","https://openalex.org/W3094429645","https://openalex.org/W3119736121","https://openalex.org/W3134435768","https://openalex.org/W3161121126","https://openalex.org/W3171708529","https://openalex.org/W3178407368","https://openalex.org/W3193598686","https://openalex.org/W3198606485","https://openalex.org/W3210606186","https://openalex.org/W4223640637","https://openalex.org/W4235435263","https://openalex.org/W4296225936","https://openalex.org/W4308405423","https://openalex.org/W4320855364","https://openalex.org/W4361287694","https://openalex.org/W4381598483","https://openalex.org/W4381943587","https://openalex.org/W4384817572","https://openalex.org/W4386194106","https://openalex.org/W4386584720","https://openalex.org/W4394061993","https://openalex.org/W4402049769","https://openalex.org/W4402064302","https://openalex.org/W4402066166","https://openalex.org/W4403505891","https://openalex.org/W4405947683","https://openalex.org/W4410363149","https://openalex.org/W4411786117","https://openalex.org/W4412473622","https://openalex.org/W4413842721","https://openalex.org/W4413842862","https://openalex.org/W4413846475","https://openalex.org/W4416368308","https://openalex.org/W7128605311","https://openalex.org/W7162108239","https://openalex.org/W7162133671"],"related_works":[],"abstract_inverted_index":{"Background:":[0],"Low-dose":[1],"spironolactone":[2,66,123,200],"is":[3,45,186,201,211],"the":[4,175],"preferred":[5,176],"fourth-line":[6,177],"treatment":[7],"for":[8,30,179],"resistant":[9],"hypertension,":[10],"but":[11],"hyperkalemia,":[12],"renal":[13,145,157],"dysfunction,":[14],"endocrine":[15],"adverse":[16],"effects,":[17],"and":[18,51,60,78,92,100,135,144,162,165,193],"monitoring":[19,163],"requirements":[20],"limit":[21],"its":[22,203],"use.":[23],"The":[24,147,183],"QUADRO":[25,85,120],"trial":[26],"provides":[27],"new":[28],"evidence":[29],"a":[31,48,97,187],"bisoprolol-containing":[32],"quadruple":[33,184],"single-pill":[34],"combination":[35],"(SPC).":[36],"Methods:":[37],"This":[38],"narrative":[39],"review":[40],"with":[41,110,207],"an":[42,139,212],"expert-viewpoint":[43],"component":[44],"based":[46],"on":[47],"focused":[49],"PubMed/MEDLINE":[50],"Scopus":[52],"search":[53],"(January":[54],"2000\u2013September":[55],"2026),":[56],"earlier":[57],"landmark":[58],"studies,":[59],"current":[61],"guidelines.":[62],"Results:":[63],"In":[64,84],"PATHWAY-2,":[65],"lowered":[67,90],"home":[68],"systolic":[69,94],"blood":[70],"pressure":[71],"(BP)":[72],"by":[73,79,96],"8.70":[74],"mmHg":[75,81,102],"versus":[76,82,103,116],"placebo":[77],"4.48":[80],"bisoprolol.":[83],"(n":[86],"=":[87],"183),":[88],"perindopril/indapamide/amlodipine/bisoprolol":[89],"office":[91,111],"24-h":[93],"BP":[95,112],"further":[98],"8.0":[99],"7.5":[101],"continued":[104],"triple":[105],"therapy":[106],"at":[107],"8":[108],"weeks,":[109],"control":[113],"in":[114,205],"66%":[115],"43%":[117],"of":[118],"patients.":[119,182],"had":[121],"no":[122],"comparator,":[124],"matched":[125],"tablet":[126],"burden":[127],"between":[128],"groups,":[129],"excluded":[130],"patients":[131,206],"already":[132],"receiving":[133],"beta-blockers,":[134],"did":[136],"not":[137],"test":[138],"adherence":[140],"advantage":[141],"or":[142],"cardiovascular":[143],"outcomes.":[146],"proposed":[148],"framework":[149],"confirms":[150],"true":[151],"resistance,":[152],"optimizes":[153],"background":[154],"therapy,":[155],"weighs":[156],"function,":[158],"potassium,":[159],"comorbidities,":[160],"tolerability,":[161],"capacity,":[164],"separates":[166],"drug-class":[167],"selection":[168],"from":[169],"formulation":[170],"choice.":[171],"Conclusions:":[172],"Spironolactone":[173],"remains":[174],"agent":[178],"most":[180],"eligible":[181],"SPC":[185],"complementary":[188],"option":[189],"when":[190,199],"all":[191],"components":[192],"fixed":[194],"doses":[195],"are":[196,216],"appropriate,":[197],"chiefly":[198],"unsuitable;":[202],"use":[204],"established":[208],"beta-blocker":[209],"indications":[210],"extrapolation.":[213],"Head-to-head":[214],"trials":[215],"needed.":[217]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}