Beta-blocker initiation under dobutamine infusion in acute advanced heart failure: a target trial emulation with observational data

Author:

Mori Yuichiro1ORCID,Inoue Kosuke23ORCID,Sato Hiroyuki4,Tsushima Takahiro5ORCID,Fukuma Shingo16ORCID

Affiliation:

1. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , 54, Shogoin-Kawahara-cho, Sakyo-Ku, Kyoto-shi, Kyoto 6068507 , Japan

2. Department of Social Epidemiology, Graduate School of Medicine, Kyoto University , Yoshida-Konoe-cho, Sakyo-ku, Kyoto-shi, Kyoto 6068315 , Japan

3. Hakubi Center for Advanced Research, Kyoto University , Yoshida-Honmachi, Sakyo-ku, Kyoto-shi, Kyoto 6068317 , Japan

4. Department of Cardiovascular Medicine, Graduate School of Medicine, Tohoku University , 1-1, Seiryo-cho, Aoba-ku, Sendai-shi, Miyagi 9808574 , Japan

5. University Hospitals Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine , 11100 Euclid Ave., Cleveland, OH 44106 , USA

6. Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Graduate School of Biomedical and Health Sciences , 1-3-2, Kagamiyama, Higashi-Hiroshima 7398511 , Japan

Abstract

Abstract Aims In patients with advanced heart failure requiring dobutamine infusion, it is usually recommended to initiate beta-blockers after weaning from dobutamine. However, beta-blockers are sometimes initiated under dobutamine infusion in a real-world scenario. The association between such early beta-blocker initiation with clinical outcomes is unknown. Therefore, this study investigates the association between initiating beta-blockers under dobutamine infusion and survival outcomes. Methods and results This observational study with a multicentre inpatient-care database emulated a pragmatic randomized controlled trial (RCT) of the beta-blocker initiation strategy. First, 1151 patients on dobutamine and not on beta-blockers on the day of heart failure admission (Day 0) were identified. Among 1095 who met eligibility criteria, patients who were eventually initiated beta-blockers under dobutamine infusion by Day 7 (early initiation strategy) were 1:1 matched to those who were not initiated (conservative strategy). The methods of cloning, censoring, and weighting were applied to emulate the target trial. Patients were followed up for up to 30 days. The primary outcome was all-cause death. Among 780 matched patients (median age, 81 years), the adjusted hazard ratio was 1.11 (95% confidence interval 0.75–1.64, P = 0.59) for the early initiation strategy. The estimated 30-day all-cause mortalities in the early initiation strategy and the conservative strategy were 19.3% (10.6–30.7) and 16.2% (9.2–25.3), respectively. The results were consistent when we used different days to determine strategies (i.e. 5 and 9) instead of 7 days. Conclusion The present observational study emulating a pragmatic RCT found no positive or negative association between beta-blocker initiation under dobutamine infusion and overall survival.

Funder

Japan Society for the Promotion of Science

Japan Science and Technology

Meiji Yasuda Life Foundation of Health and Welfare

Program for the Development of Next-generation Leading Scientists with Global Insight

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Oxford University Press (OUP)

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