{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:30:26Z","timestamp":1791419426449,"version":"4.3.3"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Ambulatory chronic heart failure patients (n=988) with normal sinus rhythm and ejection fraction &gt;45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n=492) or placebo (n=496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07;\n                    <jats:italic>P<\/jats:italic>\n                    =0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04;\n                    <jats:italic>P<\/jats:italic>\n                    =0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91;\n                    <jats:italic>P<\/jats:italic>\n                    =0.061).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.106.628347","type":"journal-article","created":{"date-parts":[[2006,7,24]],"date-time":"2006-07-24T20:25:41Z","timestamp":1153772741000},"page":"397-403","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":510,"title":["Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure"],"prefix":"10.1161","volume":"114","author":[{"given":"Ali","family":"Ahmed","sequence":"first","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Rich","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome L.","family":"Fleg","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Young","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalane W.","family":"Kitzman","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Love","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilbert S.","family":"Aronow","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Kirkwood F.","family":"Adams","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Gheorghiade","sequence":"additional","affiliation":[{"name":"From the University of Alabama at Birmingham, and VA Medical Center, Birmingham (A.A.); Washington University, St Louis, Mo (M.W.R.); National Heart, Lung, and Blood Institute, Bethesda, Md (J.L.F.); Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston (M.R.Z.); Cleveland Clinic Foundation, Cleveland, Ohio (J.B.Y.); Wake-Forest University, Winston-Salem, NC (D.W.K.); Case Western Reserve University, Cleveland, Ohio (T.E.L.); New York Medical College, Valhalla (W.S..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.113.22.f85"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.104.7.779"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00118-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-137-8-200210150-00006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.2.194"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032566"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14285-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000132482.95686.87"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(95)00065-8"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199702203360801"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi687"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0033-0620(98)80053-4"},{"key":"e_1_3_2_13_2","unstructured":"Digitalis Investigation Group. Protocol: Trial to Evaluate the Effect of Digitalis on Mortality in Heart Failure. Bethesda Md: National Heart Lung and Blood Institute; 1991."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(03)00135-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/60.10.1339"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2002.124058"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.02.083"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.07.046"},{"key":"e_1_3_2_19_2","unstructured":"Joint clinical review: new drug application 20\u2013405: DIG Study. Original NDA amendment (digoxin for heart failure). Beltsville Md: Center for Drug Evaluation and Research. Division of Cardio-Renal Drug Products; 1997."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198501313120504"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.48.3.7460209"},{"key":"e_1_3_2_22_2","first-page":"254A.","volume":"19","year":"1992","unstructured":"Eichhorn EJ, Alvarez LG, Willard JE, Grayburn PA. Digitalis improves myocardial relaxation in patients with heart failure. J Am Coll Cardiol. 1992; 19: 254A. Abstract.","journal-title":"J Am Coll Cardiol"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.84.5.1834367"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc1202.105290"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.17.2144"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.1.2736756"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1972.222.6.1398"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(83)90346-7"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2005.01.016"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.106.628347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:12:46Z","timestamp":1715562766000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.106.628347"}},"subtitle":["The Ancillary Digitalis Investigation Group Trial"],"short-title":[],"issued":{"date-parts":[[2006,8]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006,8]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.106.628347"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.106.628347","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.723706457.793511071","asserted-by":"object"}]},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,8]]},"assertion":[{"value":"2006-07-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}