Effect of sildenafil on platelet activation and mediators of vascular remodelling during LVAD support
Abstract
Introduction: Observational studies provide a signal that phosphodiesterase-5 inhibitors such as sildenafil are associated with lower mortality and ischaemic stroke during durable left ventricular assist device (LVAD) support. This study aims to determine the causal effects of sildenafil on platelet activation and circulating mediators of vascular remodelling during LVAD support.
Methods: We conducted a double-blind, randomized, placebo-controlled study to determine the effect of sildenafil on platelet activation and circulating mediators of vascular remodelling. Stable participants on LVAD support were assigned to sildenafil or placebo every 8 h for a 15-day period. Three primary endpoints were percent change in platelet activation by collagen, thromboxane (Tx) A2, and adenosine diphosphate (ADP). Secondary endpoints included changes in circulating mediators of vascular remodelling.
Results: Twenty participants were randomized. On day 15, those on sildenafil had lower collagen (-41%, -60 to -24, vs. -7%, -18 to 79, P = .038), but not TxA2 (-24%, -45 to -14 vs. 3%, -15 to 87, P = .112), and ADP (-5%, -70 to 25 vs. 31%, -29 to 242, P = .122) induced platelet activation compared to placebo. Endothelin-1 changed by -30% (-53 to 4) in the sildenafil group vs. -3% (-18 to 22) with placebo (P = .041). Angiopoietin (ang)-2 changed by -5% (-11 to -4) with sildenafil compared to 3% (-5 to 15) with placebo (P = .039), while ang-1 increased by 24% (17-54) with sildenafil and was -4%…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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