A 2020 review article comprehensively examined the treatment and prophylactic strategies for managing gastrointestinal bleeding (GIB) in patients with left ventricular assist devices (LVADs). Initial management of GIB involves supportive care with blood transfusions and withholding anticoagulation, while endoscopic evaluation remains a cornerstone for both diagnosis and hemostatic therapy when feasible. However, due to the often diffuse or recurrent nature of bleeding, especially from small bowel arteriovenous malformations (AVMs), prophylactic pharmacologic interventions have gained increasing attention. Prophylactic medications commonly assessed in literature include octreotide, thalidomide, danazol, and estrogen-based therapies. Octreotide, a somatostatin analogue, has shown promise in decreasing splanchnic blood flow and inhibiting angiogenesis, with some observational data supporting reduced bleeding recurrence. Thalidomide, with its anti-angiogenic properties via suppression of vascular endothelial growth factor (VEGF), demonstrated efficacy in small case series, though its neurotoxicity and thrombotic risks limit broader use. Danazol, a synthetic androgen, may improve mucosal integrity and has been associated with fewer bleeding episodes, though data remain limited. Estrogen-based therapies, while previously considered for angiodysplasia-associated GIB, have shown inconsistent results and are generally less favored in current practice due to side effects and lack of robust efficacy. The authors concluded that no single agent has been definitively proven to prevent GIB in all LVAD patients, and clinical decisions are often individualized based on patient history, bleeding pattern, and tolerance of pharmacologic therapies. Furthermore, there remains a need for randomized controlled trials to better define the efficacy and safety of prophylactic medications. Overall, a combination of endoscopic surveillance, tailored anticoagulation strategies, and selective use of prophylactic agents appears to offer the most pragmatic approach in reducing the burden of GIB in this population. [1]
A 2020 meta-analysis evaluated the association between angiotensin II antagonists, specifically angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), and the incidence of GIB in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs). The investigation pooled data from three retrospective cohort studies encompassing a total of 619 patients, 467 of whom received ACEI or ARB therapy. Eligible studies included in the analysis were required to report on the incidence of GIB and/or AVM-related GIB in adult CF-LVAD patients who received and did not receive ACEI/ARB therapy. The meta-analysis demonstrated a statistically significant association between ACEi/ARB use and reduced overall GIB in CF-LVAD recipients, with a pooled OR of 0.35 (95% CI, 0.22–0.56; p < 0.001; I² = 0%). However, the relationship between ACEI/ARB therapy and AVM-related GIB was not statistically significant (pooled odds ratio [OR], 0.46; 95% CI, 0.19–1.07; p = 0.07; I² = 51%). Sensitivity analyses suggested that excluding data from the largest contributing study revealed statistical significance for AVM-related bleeding, indicating potential heterogeneity in methods or diagnostic sensitivity across included studies. Dosing effects were inconclusive—though doses equivalent to >5 mg daily of lisinopril were linked to fewer major GIB events, lower doses were paradoxically associated with reduced AVM-related GIB in at least one included report. Duration of exposure was inconsistently defined across studies, and was limited by retrospective design, making it difficult to conclude causality or optimal therapeutic parameters. No differences in outcomes between ACEIs and ARBs were delineated. [2], [3]
A 2023 narrative review synthesized clinical knowledge surrounding GIB related to CF-LVAD. Based on registry analyses and small retrospective studies, the review highlighted several pharmacological interventions targeting both primary and secondary prophylaxis. Utilizing ACEi/ARB was associated with reduced GIB risk by downregulating angiogenic mediators such as TGF-β, VEGF, and angiopoietin-2. A 2019 retrospective cohort analysis demonstrated a 57% reduction in GIB with ACEi/ARB use and a dose-response threshold, although findings remain inconsistent across studies. In secondary prevention, long-acting octreotide showed favorable outcomes in multicenter retrospective series, with reductions in bleeding recurrence and need for transfusions. Other studied agents included digoxin, shown to reduce GIB incidence via HIF-1α inhibition, and omega-3 fatty acids, which in a 2018 observational cohort resulted in a 97% freedom from GIB at one year. Despite these promising pharmacologic strategies, no randomized controlled trials have been conducted, and current evidence is derived exclusively from non-randomized, registry-based, or observational datasets. The review further underscored that newer-generation devices like the HeartMate 3, while reducing thromboembolic events and possibly AVM formation due to restored pulsatility and shear stress mitigation, still confer a considerable residual GIB risk, warranting continued investigation into integrated prophylactic and therapeutic algorithms. [4]
Lastly, a 2021 network meta-analysis (NMA) assessed the efficacy of various pharmacologic interventions in preventing recurrent GIB in patients with LVAD. The analysis included 13 observational studies that compared six strategies, with four focusing on primary prevention and nine on secondary prevention of GIB. The findings revealed that thalidomide, omega-3 fatty acids, octreotide, and danazol were associated with a reduced risk of recurrent GIB. Specifically, thalidomide showed a hazard ratio (HR) of 0.016 (Credible Interval [CrI] 0.00053 to 0.12), omega-3 fatty acids had an HR of 0.088 (CrI 0.026 to 0.77), octreotide had an HR of 0.17 (CrI 0.0589 to 0.41), and danazol also had an HR of 0.17 (CrI 0.059 to 0.41). On the other hand, ACEi/ARB and digoxin did not show any significant reduction in GIB risk. Overall, the findings suggested that thalidomide, danazol, and octreotide were effective in reducing recurrent GIB, while omega-3 fatty acids were particularly helpful in lowering the risk of the primary episode of GIB in the LVAD population. However, it is important to note that the observational nature of included studies may increase the heterogeneity, and the severity of GIB can not be specified without the detailed information of endoscopy and the number of units of blood transfusion. [5]