Tolerability and Biological Effects of Long-Acting Octreotide in Patients With Continuous Flow Left Ventricular Assist Devices

Abstract

Patients with implanted continuous, nonpulsatile, left ventricular assist devices (LVADs) have increased the occurrence of gastrointestinal bleeding (GIB). Although the pathophysiology is multifactorial, there are few treatments beyond supportive care. Octreotide acetate is a somatostatin analog that reduces GIB in various patient populations. However, there are sparse case series that suggest octreotide acetate may reduce GIB in LVAD patients. This 10 patient, 28 week phase I study evaluated the safety and tolerability of octreotide acetate long-acting release (LAR) 20 mg depot injection every 4 weeks until week 16 after LVAD placement. Secondary aims were occurrence of GIB and measurement of vascular endothelial growth factor, fibrinogen, von Willebrand factor, and platelet aggregation across the study period. Ten patients were enrolled, and eight completed the study. The two study dropouts were not related to octreotide. None of the patients experienced side effects or safety concerns related to octreotide nor did GIB occur in the study population. Vascular endothelial growth factor levels were maintained in the reference range throughout the duration of the study. There did appear to be laboratory evidence of acquired von Willebrand syndrome, with mildly low platelet aggregation studies. In conclusion, octreotide acetate LAR 20 mg depot injection was safe and effective in this population.

Long-Acting Octreotide Reduces the Recurrence of Gastrointestinal Bleeding in Patients With a Continuous-Flow Left Ventricular Assist Device

“…Therefore, the risk for GI bleeding among patients in that study may not be as high as our patients. 15 In our cohort, three patients experienced pump thrombosis during octreotide therapy, possibly related to inability to maintain therapeutic anticoagulation levels due to recurrent GI bleeding.…”

“…22, 23 Measurement of GI bleeding-associated factors such as vascular endothelial growth factor and portal vein pressure before and during octreotide therapy may also be useful for optimal patient selection. 15 …”

“…14, 15 However, optimization of dosing specifically for LVAD patients is warranted. These factors, in addition to varied indications for the use of octreotide among institutions, may underlie discordant reports with some case reports showing positive effects and others showing no effect on bleeding.…”

Bleeding with the artificial heart: Gastrointestinal hemorrhage in CF-LVAD patients

“…On a case by case basis, success with octreotide - a somatostatin analogue which acts as a splanchnic vasoconstrictor and may affect angiogenesis - has been reported[64], but its application to control bleeding and prevent future hemorrhages in LVAD patients may be offset by high cost and limited outpatient use[11]. Recent small phase I trial showed octreotide potential effectiveness and general tolerability as early intervention[65] and future large prospective randomized investigations would be necessary to further define its role in LVAD population. There was anecdotal use of antihemophilic factor/vWF complex and hormonal (estrogen, desmopressin) therapy in refractory bleeding[35,66], although unclear if the patient would have benefited from repeated small intestinal evaluation prior to its initiation.…”

Multicenter Evaluation of Octreotide as Secondary Prophylaxis in Patients With Left Ventricular Assist Devices and Gastrointestinal Bleeding

“…[13][14][15][16] A recent prospective study was conducted with octreotide in stable LVAD patients and was noted to be well tolerated with no drug-related side effects or GI bleeding events observed. 17 To further elucidate the potential role of octreotide in preventing recurrent LVAD-associated GI bleeding, we conducted a retrospective, multicenter cohort study to determine the incidence of rebleeding in patients receiving secondary octreotide prophylaxis. Herein, we report the demographics and clinical characteristics associated with rebleeding versus non-rebleeding and further compare these data to a historical control group comprised patients who experienced GI bleeding in the original clinical trial of the HMII (HeartMate II) LVAD.…”