eprintid: 118328 rev_number: 43 eprint_status: archive userid: 12688 dir: disk0/00/11/83/28 datestamp: 2016-04-11 11:41:49 lastmod: 2020-05-28 10:21:55 status_changed: 2016-04-11 11:41:49 type: article metadata_visibility: show creators_name: Okumura, Naoki creators_name: Jhund, Pardeep S. creators_name: Gong, Jianjian creators_name: Lefkowitz, Martin P. creators_name: Rizkala, Adel R. creators_name: Rouleau, Jean L. creators_name: Shi, Victor C. creators_name: Swedberg, Karl creators_name: Zile, Michael R. creators_name: Solomon, Scott D. creators_name: Packer, Milton creators_name: McMurray, John J. V. creators_orcid: 0000-0003-4306-5317 creators_orcid: 0000-0002-6317-3975 title: Importance of clinical worsening of heart failure treated in the outpatient setting: evidence from the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) ispublished: pub divisions: 25200000 full_text_status: public abstract: Background—Many episodes of worsening of heart failure (HF) are treated by increasing oral therapy or intravenous treatment in the community or emergency department (ED), without hospital admission. We studied the frequency and prognostic importance of these episodes of worsening in PARADIGM-HF. Methods and Results—Outpatient intensification of HF therapy (IT) was added to an expanded composite outcome with ED visits, HF hospitalizations (HFh) and cardiovascular deaths. Examining first non-fatal events, 361/8399 patients (4.3%) had IT without a subsequent event (i.e. ED visit/HFh) within 30 days; 78/8399 (1.0%) had an ED visit without prior IT or a subsequent event within 30 days; and 1107/8399 (13.2%) had HFh without a preceding event. The risk of death (compared with "no event" patients) was similar after each manifestation of worsening - IT: HR=4.8(95%CI 3.9-5.9); ED visit: 4.5(3.0-6.7); HFh: 5.9(5.2-6.6). The expanded composite added 14% more events and shortened time to accrual of a fixed number of events. The benefit of sacubitril/valsartan over enalapril was similar to the primary outcome for the expanded composite (HR 0.79, 0.73-0.86) and was consistent across the components of the latter. Conclusions—Focusing only on HFh underestimates the frequency of worsening and the serious implications of all manifestations of worsening. For clinical trials conducted in an era of heightened efforts to avoid HFh, inclusion of episodes of outpatient treatment intensification (and ED visits) in a composite outcome adds an important number of events and shortens the time taken to accrue a target number of endpoints in an event-driven trial. date: 2016-06-07 date_type: published publication: Circulation volume: 133 number: 23 publisher: American Heart Association pagerange: 2254-2262 id_number: 10.1161/CIRCULATIONAHA.115.020729 refereed: TRUE issn: 0009-7322 copyright_holders: Copyright © 2016 American Heart Association, Inc. prior: First published in Circulation 133(23):2254-2262 repro: Reproduced in accordance with the copyright policy of the publisher uniqueid: glaseprints:2016-118328 published_online: 2016-04-20 issn_online: 1524-4539 pubmed_id: 27143684 euro_pubmed_id: 27143684 hoa_compliant: 9215 hoa_emb_len: 6 hoa_ref_pan: AB hoa_date_acc: 2016-04-08 hoa_date_pub: 2016-04-20 hoa_date_foa: 2016-04-11 hoa_version_fcd: VoR hoa_exclude: FALSE hoa_gold: TRUE rioxx2_apc_input: not required citation: Okumura, N. et al. (2016) Importance of clinical worsening of heart failure treated in the outpatient setting: evidence from the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Circulation , 133(23), pp. 2254-2262. (doi: 10.1161/CIRCULATIONAHA.115.020729 ) (PMID:27143684) document_url: https://eprints.gla.ac.uk/118328/1/118328.pdf