Effect of Angiotensin II Inhibitors on Gastrointestinal Bleeding in Patients With Left Ventricular Assist Devices

BACKGROUND Angiotensin II receptor activation may result in angiogenesis, and ultimately arteriovenous malformations (AVM), through transforming growth factor (TGF)-beta and angiopoietin-2 pathway activation. OBJECTIVES The goal of this study was to determine whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) were associated with lower risk of major gastrointestinal bleeds (GIB) and AVM-related GIBs in continuous-flow left ventricular assist device (CF-LVAD) patients. METHODS The authors reviewed HeartMate II CF-LVAD recipients between January 2009 and July 2016. Major GIBs were endoscopically confirmed requiring >= 2 U of packed red blood cells or resulting in death. ACE inhibitor/ARB dose was abstracted from medical records. ACE inhibitor/ARB exposure status was landmarked at 30 days post-operatively to avoid immortal time bias. Fine and Gray hazard models assessed the impact of ACE inhibitor/ARB therapy on major GIB and AVM-related GIB, whereas standard Cox regression assessed the impact on mortality, adjusting for baseline variables. RESULTS One-hundred and eleven patients were included with a mean 2.1 +/- 1.4 years follow-up. Patients who received an ACE inhibitor/ARB within 30 days post-operatively had a 57% reduction in the risk of major GIB (adjusted hazard ratio [aHR]: 0.43; 95% confidence interval [CI]: 0.19 to 0.97; p = 0.042) and a 63% reduction in the risk of AVM-related GIB (aHR: 0.37; 95% CI: 0.16 to 0.84; p = 0.017). When the mean daily post-operative lisinopril-equivalent ACE inhibitor/ARB dose was >5 mg, the risk of major GIB decreased in a dose-threshold manner (aHR: 0.28; 95% CI: 0.09 to 0.85; p = 0.025). CONCLUSIONS ACE inhibitor/ARB therapy is associated with a protective effect of developing GIBs in CF-LVAD patients, with a dose threshold of >5 mg of daily lisinopril equivalence, possibly due to prevention of AVM formation. (C) 2019 by the American College of Cardiology Foundation.