{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:11:00Z","timestamp":1786133460055,"version":"build-2736575974"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","funder":[{"DOI":"10.13039\/100009257","name":"ASN Foundation for Kidney Research","doi-asserted-by":"crossref","award":["Ben J. Lipps Postdoctoral Fellowship grant (2025), awarded by Kidney Cure."],"award-info":[{"award-number":["Ben J. Lipps Postdoctoral Fellowship grant (2025), awarded by Kidney Cure."]}],"id":[{"id":"10.13039\/100009257","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Many major adverse cardiovascular events happen within the first 6 months after hemodialysis initiation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Using nondialyzable\n                            <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                            -blockers at hemodialysis initiation was associated with fewer cardiovascular events than dialyzable\n                            <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                            -blockers.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      How\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blocker dialyzability affects cardiovascular outcomes in patients receiving hemodialysis remains unclear. Previous observational studies show conflicting results, and conducting clinical trials in this population has proven challenging. This uncertainty has contributed to substantial variation in\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blocker prescribing patterns across regions and clinicians.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using data from the United States Renal Data System, we identified patients receiving\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blockers on the day of starting hemodialysis and classified them into nondialyzable and dialyzable exposure groups. Geographical variations in nondialyzable and dialyzable\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blocker prescription rates across neighboring regions in each state were leveraged as an instrumental variable. The treatment effect of nondialyzable versus dialyzable\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blockers on major adverse cardiovascular events (MACE) at 6 months, 1 year, and 3 years was evaluated using instrumental variable\n                      <jats:italic toggle=\"yes\">g<\/jats:italic>\n                      -estimation methods for survival outcomes. MACE comprised myocardial infarction, stroke, and all-cause mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort of 40,313 participants from 41 US states experienced 25,720 MACE over the 3-year follow-up period (median years [interquartile range], 1.4 [0.4\u20133.0]), with more than 42% occurring during the first 6 months after hemodialysis initiation. The instrumental variable met all statistical assumptions. Nondialyzable\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blockers were associated with significantly lower risk of MACE at all three follow-up time points compared with dialyzable\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blockers (hazard ratios [95% confidence intervals], 0.82 [0.74 to 0.90], 0.85 [0.79 to 0.92], and 0.90 [0.85 to 0.96], respectively). Similar patterns were observed for each separate component of MACE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The use of nondialyzable\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blockers compared with dialyzable\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -blockers was associated with a lower risk of MACE during all time points, including the early, high-risk period in the 6 months following hemodialysis initiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001147","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:00:16Z","timestamp":1779296416000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Nondialyzable versus Dialyzable \u03b2-Blockers in Hemodialysis"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7246-1370","authenticated-orcid":false,"given":"Ali","family":"Etemadi","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-5649","authenticated-orcid":false,"given":"Sai","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-425X","authenticated-orcid":false,"given":"Wolfgang C.","family":"Winkelmayer","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-2182","authenticated-orcid":false,"given":"Maria E.","family":"Montez-Rath","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4691-1681","authenticated-orcid":false,"given":"Tara I.","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"issue":"8","key":"B1-20260713","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.2215\/CJN.10611015","article-title":"Antihypertensive medication use in older patients transitioning from chronic kidney disease to end-stage renal disease on dialysis","volume":"11","author":"Chang","year":"2016","journal-title":"Clin J Am Soc Nephrol."},{"issue":"4","key":"B2-20260713","doi-asserted-by":"crossref","first-page":"604","DOI":"10.2215\/CJN.07470717","article-title":"\u03b2-Blocker dialyzability in maintenance hemodialysis patients: a randomized clinical trial","volume":"13","author":"Tieu","year":"2018","journal-title":"Clin J Am Soc Nephrol."},{"key":"B3-20260713","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ijcard.2017.01.015","article-title":"Cardiovascular impact in patients undergoing maintenance hemodialysis: clinical management considerations","volume":"232","author":"Chirakarnjanakorn","year":"2017","journal-title":"Int J Cardiol."},{"issue":"3","key":"B4-20260713","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/nep.12362","article-title":"The rationale and design of the beta-blocker to LOwer CArdiovascular dialysis events (BLOCADE) feasibility study","volume":"20","author":"Roberts","year":"2015","journal-title":"Nephrology."},{"issue":"24","key":"B5-20260713","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1001\/jama.2022.21383","article-title":"Target trial emulation: a framework for causal inference from observational data","volume":"328","author":"Hern\u00e1n","year":"2022","journal-title":"JAMA."},{"issue":"5","key":"B6-20260713","doi-asserted-by":"crossref","first-page":"100460","DOI":"10.1016\/j.xkme.2022.100460","article-title":"\u03b2-Blocker use and cardiovascular outcomes in hemodialysis: a systematic review","volume":"4","author":"Tella","year":"2022","journal-title":"Kidney Med."},{"issue":"12","key":"B7-20260713","doi-asserted-by":"crossref","first-page":"e0279680","DOI":"10.1371\/journal.pone.0279680","article-title":"Impact of type of dialyzable beta-blockers on subsequent risk of mortality in patients receiving dialysis: a systematic review and meta-analysis","volume":"17","author":"Yeh","year":"2022","journal-title":"PLoS One."},{"issue":"3","key":"B8-20260713","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1053\/j.ajkd.2018.02.350","article-title":"A comparative study of carvedilol versus metoprolol initiation and 1-year mortality among individuals receiving maintenance hemodialysis","volume":"72","author":"Assimon","year":"2018","journal-title":"Am J Kidney Dis."},{"issue":"1","key":"B10-20260713","doi-asserted-by":"crossref","first-page":"14","DOI":"10.2202\/1557-4679.1072","article-title":"Preference-based instrumental variable methods for the estimation of treatment effects: assessing validity and interpreting results","volume":"3","author":"Brookhart","year":"2007","journal-title":"Int J Biostat."},{"issue":"13","key":"B11-20260713","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1002\/sim.6128","article-title":"Instrumental variable methods for causal inference","volume":"33","author":"Baiocchi","year":"2014","journal-title":"Stat Med."},{"issue":"1","key":"B13-20260713","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s12874-021-01440-5","article-title":"Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review","volume":"21","author":"Bosco","year":"2021","journal-title":"BMC Med Res Methodol."},{"issue":"8","key":"B14-20260713","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1097\/MLR.0b013e3181e41bb2","article-title":"A new method to isolate local-area practice styles in prescription use as the basis for instrumental variables in comparative effectiveness research","volume":"48","author":"Fang","year":"2010","journal-title":"Med Care."},{"issue":"1","key":"B15-20260713","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/widm.53","article-title":"Algorithms for hierarchical clustering: an overview","volume":"2","author":"Murtagh","year":"2012","journal-title":"WIREs Data Mining Knowledge Discov."},{"issue":"3","key":"B16-20260713","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/EDE.0000000000000262","article-title":"Instrumental variable estimation in a survival context","volume":"26","author":"Tchetgen Tchetgen","year":"2015","journal-title":"Epidemiology."},{"issue":"1","key":"B17-20260713","doi-asserted-by":"crossref","first-page":"20180024","DOI":"10.1515\/em-2018-0024","article-title":"Instrumental variable estimation with the R package ivtools","volume":"8","author":"Sjolander","year":"2019","journal-title":"Epidemiologic Methods."},{"issue":"3","key":"B18-20260713","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2307\/2171753","article-title":"Instrumental variables regression with weak instruments","volume":"65","author":"Staiger","year":"1997","journal-title":"Econometrica."},{"issue":"15","key":"B19-20260713","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1002\/sim.4780141510","article-title":"Graphical methods for assessing violations of the proportional hazards assumption in cox regression","volume":"14","author":"Hess","year":"1995","journal-title":"Stat Med."},{"key":"B20-20260713","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J Stat Softw."},{"issue":"11","key":"B21-20260713","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1093\/ndt\/gfaa058","article-title":"\u03b2-blocker dialyzability and the risk of mortality and cardiovascular events in patients undergoing hemodialysis","volume":"35","author":"Wu","year":"2020","journal-title":"Nephrol Dial Transplant."},{"issue":"1","key":"B22-20260713","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12872-016-0233-3","article-title":"Effectiveness comparison of cardio-selective to non-selective \u03b2-blockers and their association with mortality and morbidity in end-stage renal disease: a retrospective cohort study","volume":"16","author":"Shireman","year":"2016","journal-title":"BMC Cardiovasc Disord."},{"issue":"5","key":"B23-20260713","doi-asserted-by":"crossref","first-page":"sfae087","DOI":"10.1093\/ckj\/sfae087","article-title":"Comparison of \u03b2-blocker agents and mortality in maintenance hemodialysis patients: an international cohort study","volume":"17","author":"Toye","year":"2024","journal-title":"Clin Kidney J."},{"issue":"10","key":"B24-20260713","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.3390\/biomedicines11102838","article-title":"Influence of different types of \u03b2-blockers on mortality in patients on hemodialysis","volume":"11","author":"Kang","year":"2023","journal-title":"Biomedicines."},{"issue":"4","key":"B25-20260713","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1681\/ASN.2014040324","article-title":"\u03b2-Blocker dialyzability and mortality in older patients receiving hemodialysis","volume":"26","author":"Weir","year":"2015","journal-title":"J Am Soc Nephrol."},{"issue":"9","key":"B26-20260713","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1093\/aje\/kwg231","article-title":"Evaluating medication effects outside of clinical trials: new-user designs","volume":"158","author":"Ray","year":"2003","journal-title":"Am J Epidemiol."},{"issue":"12","key":"B27-20260713","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.2215\/CJN.02680314","article-title":"Intradialytic hypotension and risk of cardiovascular disease","volume":"9","author":"Stef\u00e1nsson","year":"2014","journal-title":"Clin J Am Soc Nephrol."},{"issue":"12","key":"B28-20260713","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1093\/ndt\/gfg450","article-title":"The effect of frequent or occasional dialysis-associated hypotension on survival of patients on maintenance haemodialysis","volume":"18","author":"Tisl\u00e9r","year":"2003","journal-title":"Nephrol Dial Transplant."},{"issue":"2","key":"B29-20260713","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/hdi.12138","article-title":"Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome","volume":"18","author":"Sands","year":"2014","journal-title":"Hemodial Int."},{"issue":"8","key":"B30-20260713","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/pds.5614","article-title":"Bias amplification of unobserved confounding in pharmacoepidemiological studies using indication-based sampling","volume":"32","author":"Ahlqvist","year":"2023","journal-title":"Pharmacoepidemiol Drug Saf."},{"issue":"23","key":"B31-20260713","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1001\/jama.2011.822","article-title":"Surveillance bias in outcomes reporting","volume":"305","author":"Haut","year":"2011","journal-title":"JAMA."},{"issue":"6","key":"B32-20260713","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/pds.1908","article-title":"Instrumental variable methods in comparative safety and effectiveness research","volume":"19","author":"Brookhart","year":"2010","journal-title":"Pharmacoepidemiol Drug Saf."}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:34:18Z","timestamp":1786131258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001147"}},"subtitle":["A Target Trial Emulation Study"],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":30,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001147","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"2026-03-03","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}