Dose-response relationship seen
Angiotensin II antagonists may help prevent GI bleeding among heart failure patients with continuous-flow left ventricular assist devices (LVADs), a retrospective study suggested.
Taking ACE inhibitors or angiotensin receptor blockers (ARBs) at any point within the first 30 days following LVAD placement was associated with a reduced subsequent risk of major GI bleeds (15% vs 31%, adjusted HR 0.43, 95% CI 0.19-0.97).
GI bleeds stemming from endoscopy-confirmed arteriovenous malformations (AVMs) were also less common with use of either class of medication (8% vs 21%, adjusted HR 0.37, 95% CI 0.16-0.84) over a 2-year follow-up, researchers led by Maureen Converse, PharmD, of the University of Florida Health Shands Hospital in Gainesville, reported in the April 16 issue of the Journal of the American College of Cardiology.
The reduced risk of major GI bleeding was only seen for patients on at least 5 mg daily lisinopril-equivalent medication (adjusted HR 0.28, 95% CI 0.09-0.85).
"ACE inhibitor/ARB therapy should be considered in all continuous-flow LVAD patients who can tolerate angiotensin II antagonism," the investigators suggested.
Other benefits to ACE inhibitors and ARBs include blood pressure control and renin-angiotensin-aldosterone system inhibition, noted an accompanying editorial by Joseph Rogers, MD, and Adam DeVore, MD, MHS, both of the Duke Clinical Research Institute in Durham, North Carolina.
"In our opinion, these reasons are sufficient to implore us to prescribe and optimize conventional heart failure medical therapy for patients on LVAD support early and often: early after implantation and at each clinical encounter," they urged.
Converse's study included a review of the medical records of 111 heart failure patients who got a HeartMate II continuous-flow LVAD from January 2009 through July 2016 at the Medical University of South Carolina. Patients were excluded if they had a GI bleed in the first 30 days or did not keep the HeartMate II for that entire initial period.
Two-thirds of the cohort got an ACE inhibitor/ARB at some point in the first 30 days, and this group generally shared similar characteristics as peers who didn't get the therapy.
Major GI bleeds were defined as requiring at least two units of packed red blood cells or resulting in death.
"GI bleeding on continuous-flow LVAD therapy occurs in approximately one-third of patients, and recurrent GI bleeds can be especially frustrating for patients and caregivers. These bleeds require frequent hospitalizations, transfusions, and repeat endoscopic procedures," Rogers and DeVore pointed out.
"Given that the use of ACE inhibitors and ARBs was not randomly allocated, making causal inferences is not possible. However, the observed treatment effect is remarkable and worth considering in the context of other evidence," they wrote.
The findings confirm those of a 2017 observational study linking ACE inhibitor/ARB therapy with reduced GI bleeding risk.
Continuous-flow LVADs are thought to cause GI bleeds through the hypoperfusion of the GI mucosa and subsequent angiogenesis that results in crumbly vessels prone to bleeding, the authors noted. "ACE inhibitor/ARB therapy may protect against angiogenesis by directly blocking angiotensin II formation or by antagonism of the angiotensin type 1 receptor."
Aside from the modest sample size, limitations of the study include its single-center and retrospective nature.
"We simply do not know the reasons patients were treated with an ACE inhibitor or ARB, but it is likely that patients doing well on LVAD support with better end-organ function were selected for treatment," according to Rogers and DeVore.
"Although there remains a significant amount of work to do to understand the best way to optimize medical therapy for patients on LVAD support, for now, the available evidence suggests that the right thing to do is the most logical, treat heart failure patients with heart failure medical therapy," they concluded.
Converse and Rogers disclosed no relevant conflicts of interest.
DeVore reported research funding from Akros Medical, Amgen, the American Heart Association, Bayer, Luitpold Pharmaceuticals, the National Heart, Lung, and Blood Institute, and Novartis as well as consulting for Novartis.
Journal of the American College of Cardiology
Source Reference: Converse MP, et al "Effect of angiotensin II inhibitors on gastrointestinal bleeding in patients with left ventricular assist devices" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2019.01.051.
Journal of the American College of Cardiology
Source Reference: Rogers JG, DeVore AD "RAAS inhibition to prevent GI bleeding: another reason to do the right thing" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2019.01.052.
Read the original article on Medpage Today: LVAD-Related GI Bleeding: Another Reason to Take Heart Failure Drugs