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Does the use of renin-angiotensin system inhibitors have any association with reduction in atrial fibrillation and adverse events for patients undergoing cardiac surgery?
This systematic review and meta-analysis involving 11 unique studies with 27 885 patients undergoing cardiac surgery found no additional association between preoperative renin-angiotensin system inhibitor therapy and a reduced risk of postoperative atrial fibrillation, stroke, death, or hospitalization.
The results provide no support for the routine use of renin-angiotensin system inhibitors for the possible prevention of postoperative atrial fibrillation and adverse events in patients undergoing cardiac surgery.
Postoperative atrial fibrillation (POAF) is a well-known complication after cardiac surgery. Renin-angiotensin system inhibitors (RASIs) have been suggested as an upstream therapy for selected patients with AF; however, evidence in the surgical setting is limited.
To evaluate the role of preoperative RASIs in prevention of POAF and adverse events for patients undergoing cardiac surgery.
The PubMed database and the Cochrane Library from inception until December 31, 2018, were searched by using the keywords renin-angiotensin system inhibitors OR angiotensin-converting enzyme inhibitors OR angiotensin receptor blocker OR aldosterone antagonist AND cardiac surgery. ClinicalTrials.gov was searched from inception until December 31, 2018, by using the keywords postoperative atrial fibrillation.
Randomized clinical trials (RCTs) and observational studies comparing the association between preoperative RASI treatment vs no preoperative RASI treatment (control group) and the incidence of POAF were identified. Eleven unique studies met the selection criteria.
Data Extraction and Synthesis
Pooled analysis was performed using a random-effects model. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall effect. Metaregression was conducted to explore potential risk of bias.
Main Outcomes and Measures
The primary outcome was POAF, and the secondary outcomes included rates of stroke and mortality and duration of hospitalization.
Eleven unique studies involving 27 885 unique patients (74.4% male; median age, 65 years [range, 58.5-74.5 years]) were included. Compared with the control group, the RASI group did not have a significantly reduced risk of POAF (odds ratio [OR], 1.04; 95% CI, 0.91-1.19; P = .55; z = 0.60), stroke (OR, 0.86; 95% CI, 0.62-1.19; P = .37; z = 0.90; without significant heterogeneity, P = .11), death (OR, 1.07; 95% CI, 0.85-1.35; P = .56; z = 0.59; without significant heterogeneity, P = .12), composite adverse cardiac events (OR, 1.04; 95% CI, 0.91-1.18; P = .58; z = 0.56), or a reduced hospital stay (weighted mean difference, −0.04; 95% CI, −1.05 to 0.98; P = .94; z = 0.07) using a random-effects model. Pooled analysis focusing on RCTs showed consistent results. The primary overall effect was maintained in sensitivity and subgroup analyses. Metaregression showed that male sex was significantly associated with POAF (τ2 = 0.0065; z = 3.47; Q = 12.047; P < .001) and that use of β-blockers was associated with a significantly reduced risk in developing POAF (τ2 = 0.018; z = −2.24; Q = 5.0091; P = .03).
Conclusions and Relevance
The findings from this study suggest that preoperative RASI treatment does not offer additional benefit in reducing the risk of POAF, stroke, death, and hospitalization in the setting of cardiac surgery. The results provide no support for conventional use of RASIs for the possible prevention of POAF and adverse events in patients undergoing cardiac surgery; further randomized data, particularly among those patients with heart failure, are needed.
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Accepted for Publication: April 1, 2019.
Published: May 31, 2019. doi:10.1001/jamanetworkopen.2019.4934
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Chen S et al. JAMA Network Open.
Corresponding Author: Shaojie Chen, MD, PhD , Cardioangiologisches Centrum Bethanien, Frankfurt Academy for Arrhythmias, Medizinische Klinik III, Agaplesion Markus Krankenhaus, Wilhelm-Epstein Straße 4, Frankfurt am Main, Germany, 60431 (firstname.lastname@example.org).
Author Contributions: Dr Chen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Chen, Martinek, Yin.
Acquisition, analysis, or interpretation of data: Chen, Acou, Kiuchi, Meyer, Sommer, Martinek, Schratter, Andrea, Ling, Liu, Hindricks, Pürerfellner, Krucoff, Schmidt, Chun.
Drafting of the manuscript: Chen, Kiuchi.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Chen, Kiuchi, Martinek.
Administrative, technical, or material support: Meyer, Schratter, Ling, Liu, Hindricks, Krucoff, Chun.
Supervision: Sommer, Martinek, Liu, Yin, Pürerfellner, Schmidt, Chun.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank all the participants in this study for their scientific contribution.
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