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JAMA Netw Open. 2019 May 3;2(5):e194934. doi: 10.1001/jamanetworkopen.2019.4934.

Association of Preoperative Renin-Angiotensin System Inhibitors With Prevention of Postoperative Atrial Fibrillation and Adverse Events: A Systematic Review and Meta-analysis.

Author information

Cardioangiologisches Centrum Bethanien, Frankfurt Academy for Arrhythmias, Medizinische Klinik III, Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany.
Department of Cardiology, AZ Delta, Roeselare, Belgium.
School of Medicine, Royal Perth Hospital Unit, University of Western Australia, Perth.
Klinik für Kardiologie mit Schwerpunkt Elektrophysiologie, Universitäres Herzzentrum Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg.
German Centre for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Germany.
Klinik für Elektrophysiologie/Rhythmologie, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
Abteilung der Elektrophysiologie, Herzzentrum Universität Leipzig, Leipzig, Germany.
Abteilung der Kardiologie, Akademisches Lehrkrankenhaus der Elisabethinen, Ordensklinikum Linz Elisabethinen, Linz, Austria.
Medizinische Abteilung mit Kardiologie, Krankenhaus Hietzing Wien, Vienna, Austria.
Department of Cardiology, Sul Fluminense University Hospital, Vassouras, Brazil.
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Cardiac Arrhythmia Therapeutic Service Center, Chongqing, China.
Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Medicine and Cardiology, Duke University Medical Center and Duke Clinical Research Institute, Durham, North Carolina.



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.

Data Sources:

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. was searched from inception until December 31, 2018, by using the keywords postoperative atrial fibrillation.

Study Selection:

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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