Renin-angiotensin system blockade does not attenuate abdominal aortic aneurysm growth, rupture rate, or perioperative mortality after elective repair

Objective: The objective of this study was to summarize the literature regarding the effects of renin-angiotensin system blockade (RASB) using angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) on human abdominal aortic aneurysm (AAA) growth, rupture, and perioperative mortality. Methods: We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Our review protocol was registered at the International Prospective Register of Systematic Reviews (CRD42016054082). We searched the Cochrane Central Register of Controlled Trials database, MEDLINE, and Embase from inception to 2017 for studies examining the effects of ACEi or ARB treatment on AAA growth, rupture, or perioperative mortality. Review, abstraction, and quality assessment were conducted in duplicate, and a third author resolved discrepancies. We assessed study quality using the Cochrane and Newcastle-Ottawa scales. We used randomeffects models to calculate pooled mean differences and odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was quantified using the I-2 statistic. Results: Our search yielded 525 articles. One randomized and seven observational studies involving 35,448 patients were included. Inter-rater agreement was excellent (k = 0.78), and risk of bias was low to moderate. All studies investigated ACEis, three studies investigated ARBs, and two studies included a composite RASB group consisting of ACEi or ARB users. Five studies assessed AAA growth, two assessed rupture rate, and one reported 30-day mortality after elective open repair. There was no difference in AAA growth rate between RASB and control (mean difference, 0.03 mm/y; 95% CI, - 0.40 to 0.46; P =.88; I-2 = 60%). No protective effect of RASB (OR, 0.92; 95% CI, 0.72, 1.16; P =.47; I-2 = 90%) was demonstrated for AAA rupture. Finally, RASB increased 30-day mortality in patients undergoing elective open AAA repair (OR, 5; 95% CI, 1.4, 27) according to a single well-adjusted study. Conclusions: RASB does not appear to affect AAA growth and rupture rate but increases elective perioperative mortality. The small number of heterogeneous, retrospective studies and limited long-term follow-up preclude a definitive dismissal of RASB as pharmacotherapy for AAA. Prospective, long-term data are needed to clarify the effect of RASB on AAA growth, rupture, and perioperative mortality.