Angiotensin-II and Thromboembolic Events: A Systematic Review

OBJECTIVES: To evaluate and synthesize the existing evidence for the association of angiotensin-II with thromboembolic events. DATA SOURCES: PubMed, Scopus, and CENTRAL databases. STUDY SELECTION: This systematic review included randomized trials and comparative observational studies that reported on the occurrence of venous and/or arterial thromboembolic events in adult patients receiving treatment for shock with angiotensin-II vs. a comparator. DATA EXTRACTION: A total of 1689 records were screened by two independent investigators. Seven studies were deemed eligible for inclusion, encompassing 1461 patients. This included two randomized controlled trials and five nonrandomized studies of intervention. Data were extracted independently and in duplicate. Risk of bias assessments were performed using the Risk of Bias 2 and Risk Of Bias In Nonrandomized Studies of Interventions tools. DATA SYNTHESIS: The included studies reported on a variety of individual and composite thromboembolic events as exploratory endpoints. Overall, they demonstrated an elevated risk of bias, predominantly related to confounding, measurement of outcomes and selection of reported results, which precluded quantitative synthesis. Within these limitations, we found that thromboembolic event rates were similar between the angiotensin-II and comparator groups. Venous thromboembolic events were described in 8.8% of patients receiving angiotensin-II and 9.4% of controls, while arterial thromboembolic events were reported in 11.3% and 12.7%, respectively. Total event rates were broadly comparable when utilizing data derived from the primary publications and when adjusted for the U.S. Food and Drug Administration account of trial data. CONCLUSIONS: Published evidence does not currently support or refute an association between angiotensin-II and an increased risk of venous or arterial thromboembolic events. Given the limited quality of available data, future studies should explicitly define diagnostic and reporting criteria for such events.