Increased bleeding risk with phosphodiesterase‐5 inhibitors after left ventricular assist device implantation

Abstract

Aims Therapy with phosphodiesterase-5 inhibitors (PDE5Is) after left ventricular assist device (LVAD) implantation has been associated with lower mortality and device thrombosis but increased risk for post-operative and gastrointestinal bleeding. We aimed to evaluate the impact of long-term PDE5Is on the overall bleeding risk after LVAD implantation. Methods and resultsWe retrospectively included patients who received a continuous-flow LVAD at our site and were prescribed with long-term oral PDE5Is after discharge from the index hospitalization. The primary endpoint was the occurrence of bleeding at 12 month follow-up. Secondary endpoints were all-cause death and the combination of bleeding and all-cause death. Our analysis included 109 patients of whom 75 (69%) received long-term PDE5Is. Mean age was 56 years, and 85% were male. At 12 months, 19 (17%) patients experienced at least one bleeding event. Patients on PDE5Is had higher bleeding rates (23% vs. 6%, P = 0.03) and more bleeding events per patient-year (0.32 vs. 0.06, P = 0.03) compared with patients not on PDE5Is. While overall bleeding incidence was excessively higher in the PDE5I group, there were no significant differences in the incidence of major bleeding (19% vs. 6%, P = 0.08) and gastrointestinal bleeding (11% vs. 3%, P = 0.18). Kaplan-Meier analysis revealed higher cumulative incidence of bleeding for the PDE5I group (log rank = 0.04) with no difference on all-cause death (log rank = 0.67) and the combination of bleeding and all-cause death (log rank = 0.13). Hospitalizations for bleeding and their duration were numerically higher in the PDE5I group (0.28 vs. 0.03, P = 0.07 and 2.4 vs. 0.2, P = 0.07, respectively). Conclusions Phosphodiesterase-5 inhibitor treatment after LVAD implantation is associated with increased bleeding risk after LVAD implantation. The safety of long-term PDE5Is in LVAD patients remains unclear and needs to be further clarified in prospective studies with randomized study design.

Post-Implant Phosphodiesterase-5 Inhibitors in Patients with Left Ventricular Assist Device: A Systematic Review and Meta-Analysis

“…The characteristics of the included studies are summarized in Table 1 . Among the 258 articles in Pubmed, Scopus, and CENTRAL that were retrieved, 15 studies were included in the qualitative synthesis, and 9 studies were included in the quantitative synthesis [ 11 , 12 , 13 , 22 , 23 , 24 , 25 , 26 , 27 ]. The level of agreement between the two reviewers was “almost perfect” (kappa = 0.972; 95% CI: 0.917, 1.000).…”

“…The level of agreement between the two reviewers was “almost perfect” (kappa = 0.972; 95% CI: 0.917, 1.000). The study cohort was prospective in three studies [ 11 , 12 , 13 ] and retrospective in twelve studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The included studies were conducted in Australia [ 28 ], the United States of America [ 7 , 11 , 12 , 13 , 23 , 25 , 26 , 28 , 29 , 30 , 31 ], Lebanon [ 29 ], and Germany [ 22 , 27 ].…”

“…PDE-5i also exhibit antiplatelet and antithrombotic actions. In this regard, not surprisingly, several studies have reported an association between PDE-5i and gastrointestinal bleeding [ 11 , 12 , 22 , 23 , 24 , 25 , 27 , 37 ]. This might be explained by the fact that PDE-5i exhibit antiplatelet and antithrombotic actions by potentiating the nitric oxide–mediated inhibition of platelet aggregation through the blockade of cGMP degradation [ 39 , 40 , 41 ].…”

Loss of PKGIβ/IRAG1 Signaling Causes Anemia-Associated Splenomegaly

“…Hence, cGMP signaling is relevant for different forms of anemia. However, cGMP modulators such as sGC stimulators and PDE5 inhibitors can also induce bleeding by inhibition of platelet function [36,37]. This must be considered in the therapy.…”

Phosphodiesterase‐5 inhibitors for left ventricular assist device implantation complicated by right ventricular failure

“…This is based on retrospective studies that demonstrated reduction of pulmonary artery (PA) pressure and pulmonary vascular resistance (PVR) in LVAD recipients receiving sildenafil 1 . Despite lack of robust evidence, long‐term PDE5I therapy beyond the post‐operative period is reported in up to 69% of LVAD recipients 2–4 and mainly aims at treating or preventing right ventricular (RV) failure 5 . Lately, controversial data regarding PDE5I were published, causing both enthusiasm and caution, because their use was associated with improved survival and lower rates of LVAD thrombosis but also with increased bleeding risk 6–8 .…”