{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:38:55Z","timestamp":1785494335207,"version":"3.56.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH-1103602C, TCVGH-1103601D, and TCVGH-1113602D"],"award-info":[{"award-number":["TCVGH-1103602C, TCVGH-1103601D, and TCVGH-1113602D"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Heart failure with reduced ejection fraction (HFrEF) poses significant health risks. Midodrine for maintaining blood pressure in HFrEF, requires further safety investigation. This study explores midodrine\u2019s safety in HFrEF through extensive matched analysis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Patients with HFrEF (LVEF &amp;lt;50%) without malignancy, non-dialysis dependence, or non-orthostatic hypotension, were enrolled between 28 August 2013, and 27 August 2023. Propensity score matching (PSM) created 1:1 matched groups. Outcomes included mortality, stage 4 and 5 chronic kidney disease (CKD), emergency room (ER) visits, intensive care unit (ICU) admissions, hospitalizations, and respiratory failure. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for each outcome, and Kaplan-Meier survival analysis was performed. Subgroup analyses were conducted based on gender, age (20-&amp;lt;65 vs. \u226565), medication refill frequency, and baseline LVEF.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> After 1:1 PSM, 5813 cases were included in each group. The midodrine group had higher risks of respiratory failure (HR: 1.16, 95% CI: 1.08\u20131.25), ICU admissions (HR: 1.14, 95% CI: 1.06\u20131.23), hospitalizations (HR: 1.21, 95% CI: 1.12\u20131.31), and mortality (HR: 1.090, 95% CI: 1.01\u20131.17). Interestingly, midodrine use reduced ER visits (HR: 0.77, 95% CI: 0.71\u20130.83). Similar patterns of lower ER visit risk and higher risks for ICU admissions, respiratory failure, and overall hospitalizations were observed in most subgroups.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In this large-scale study, midodrine use was associated with reduced ER visits but increased risks of respiratory failure, prolonged ICU stays, higher hospitalizations, and elevated mortality in HFrEF patients. Further research is needed to clarify midodrine\u2019s role in hemodynamic support and strengthen existing evidence.<\/jats:p>","DOI":"10.3389\/fphar.2024.1367790","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T13:13:56Z","timestamp":1709730836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Safety of midodrine in patients with heart failure with reduced ejection fraction: a retrospective cohort study"],"prefix":"10.3389","volume":"15","author":[{"given":"Ming-Ju","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Feng","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2023055","DOI":"10.4178\/epih.e2023055","article-title":"Association of blood pressure measurements in sitting, supine, and standing positions with the 10-year risk of mortality in Korean adults","volume":"45","author":"Baik","year":"2023","journal-title":"Epidemiol. health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/j.jacc.2012.12.038","article-title":"Heart failure\u2013associated hospitalizations in the United States","volume":"61","author":"Blecker","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1159\/000494806","article-title":"The impact of midodrine on outcomes in patients with intradialytic hypotension","volume":"48","author":"Brunelli","year":"2018","journal-title":"Am. J. Nephrol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e009806","DOI":"10.1161\/JAHA.118.009806","article-title":"Guideline-directed medical therapy for patients with heart failure with midrange ejection fraction: a patient-pooled analysis from the kor HF and kor AHF registries","volume":"7","author":"Choi","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"B5","article-title":"Alpha-1 receptor agonists","volume-title":"StatPearls","author":"Dean II","year":"2023"},{"key":"B6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/s0735-1097(02)01943-5","article-title":"Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients","volume":"40","author":"Dries","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1056\/NEJM200004133421502","article-title":"Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy","volume":"342","author":"Felker","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ejim.2022.08.031","article-title":"Might midodrine be useful in patients with decompensated and worsening chronic heart failure?","volume":"105","author":"Fern\u00e1ndez-Fern\u00e1ndez","year":"2022","journal-title":"Eur. J. Intern. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"003246","DOI":"10.12890\/2022_003246","article-title":"Use of midodrine in heart failure: two case reports and a review of the literature","volume":"9","author":"Hajjiah","year":"2022","journal-title":"Eur. J. Case Rep. Intern Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1093\/eurheartj\/ehy615","article-title":"Managing the patient with heart failure in the emergency department","volume":"39","author":"Hasin","year":"2018","journal-title":"Eur. heart J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1161\/01.cir.88.1.107","article-title":"Survival after the onset of congestive heart failure in Framingham Heart Study subjects","volume":"88","author":"Ho","year":"1993","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1056\/NEJMsa0803563","article-title":"Rehospitalizations among patients in the Medicare fee-for-service program","volume":"360","author":"Jencks","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1002\/ejhf.1594","article-title":"Survival of patients with chronic heart failure in the community: a systematic review and meta-analysis","volume":"21","author":"Jones","year":"2019","journal-title":"Eur. J. heart Fail."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1056\/NEJMoa020265","article-title":"Long-term trends in the incidence of and survival with heart failure","volume":"347","author":"Levy","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.amjcard.2007.11.061","article-title":"Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study)","volume":"101","author":"Loehr","year":"2008","journal-title":"Am. J. Cardiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/acem.12878","article-title":"Diagnosing acute heart failure in the emergency department: a systematic review and meta-analysis","volume":"23","author":"Martindale","year":"2016","journal-title":"Acad. Emerg. Med. official J. Soc. Acad. Emerg. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"757","DOI":"10.2165\/00003495-198938050-00004","article-title":"Midodrine A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders","volume":"38","author":"McTavish","year":"1989","journal-title":"Drugs"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1097\/MEJ.0000000000000411","article-title":"Disposition of emergency department patients diagnosed with acute heart failure: an international emergency medicine perspective","volume":"24","author":"Mir\u00f3","year":"2017","journal-title":"Eur. J. Emerg. Med. official J. Eur. Soc. Emerg. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1053\/j.ajkd.2011.12.023","article-title":"Survival in patients treated by long-term dialysis compared with the general population","volume":"59","author":"Nordio","year":"2012","journal-title":"Am. J. kidney Dis. official J. Natl. Kidney Found."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/j.amjcard.2020.01.037","article-title":"Cardiovascular safety considerations in the treatment of neurogenic orthostatic hypotension","volume":"125","author":"Olshansky","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.parkreldis.2020.04.011","article-title":"The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension","volume":"75","author":"Palma","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1093\/ndt\/gfh420","article-title":"Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review","volume":"19","author":"Prakash","year":"2004","journal-title":"Nephrol. dialysis, Transplant. official Publ. Eur. Dialysis Transpl. Assoc. - Eur. Ren. Assoc."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1001\/jama.289.19.2517","article-title":"Race, quality of care, and outcomes of elderly patients hospitalized with heart failure","volume":"289","author":"Rathore","year":"2003","journal-title":"Jama"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e648","DOI":"10.1097\/CCM.0000000000003814","article-title":"Continuation of newly initiated midodrine therapy after intensive care and hospital discharge: a single-center retrospective study","volume":"47","author":"Rizvi","year":"2019","journal-title":"Crit. care Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e628","DOI":"10.1097\/CCM.0000000000003121","article-title":"Trends in use of midodrine in the ICU: a single-center retrospective case series","volume":"46","author":"Rizvi","year":"2018","journal-title":"Crit. care Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1080\/08860220802249025","article-title":"Midodrine-induced vascular ischemia in a hemodialysis patient: a case report and literature review","volume":"30","author":"Rubinstein","year":"2008","journal-title":"Ren. Fail."},{"key":"B27","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1056\/NEJMp1204431","article-title":"The growing role of emergency departments in hospital admissions","volume":"367","author":"Schuur","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/s0735-1097(21)02037-4","article-title":"Prevalence of midodrine use in patients admitted with systolic congestive heart failure","volume":"77","author":"Scoma","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"B29","first-page":"203","article-title":"Renal failure caused by eyedrops containing phenylephrine in a case of retinopathy of prematurity","volume":"50","author":"Shinomiya","year":"2003","journal-title":"J. Med. investigation JMI"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2050313X221100400","DOI":"10.1177\/2050313X221100400","article-title":"Midodrine to optimize heart failure therapy in patients with concurrent hypotension","volume":"10","author":"Shiu","year":"2022","journal-title":"SAGE open Med. case Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.ejim.2022.09.009","article-title":"Might midodrine be useful in patients with decompensated and worsening chronic heart failure? Author's reply","volume":"105","author":"Sinagra","year":"2022","journal-title":"Eur. J. Intern. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13613-020-00737-w","article-title":"Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study","volume":"10","author":"Tremblay","year":"2020","journal-title":"Ann. intensive care"},{"key":"B33","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1007\/BF02849965","article-title":"Midodrine: insidious development of urologic adverse effects in patients with spinal cord injury: a report of 2 cases","volume":"24","author":"Vaidyanathan","year":"2007","journal-title":"Adv. Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1001\/jama.2017.2841","article-title":"Association between US norepinephrine shortage and mortality among patients with septic shock","volume":"317","author":"Vail","year":"2017","journal-title":"Jama"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1161\/CIR.0b013e3181f9a223","article-title":"Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association","volume":"122","author":"Weintraub","year":"2010","journal-title":"Circulation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s13181-016-0574-4","article-title":"Severe hypertension and bradycardia secondary to midodrine overdose","volume":"13","author":"Wong","year":"2017","journal-title":"J. Med. Toxicol. official J. Am. Coll. Med. Toxicol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jacc.2017.11.025","article-title":"2017 acc Expert Consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology task force on Expert Consensus decision pathways","volume":"71","author":"Yancy","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1111\/j.1751-7133.2008.00042.x","article-title":"The use of midodrine in patients with advanced heart failure","volume":"15","author":"Zakir","year":"2009","journal-title":"Congest. heart Fail. (Greenwich, Conn)"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1367790\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T13:13:59Z","timestamp":1709730839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1367790\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,6]]},"references-count":38,"alternative-id":["10.3389\/fphar.2024.1367790"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1367790","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,6]]},"article-number":"1367790"}}