Enoximone 100mg/20ml solution for injection ampoules

BackgroundInotropes play a significant role in the treatment of cardiogenic shock (CS). Phosphodiesterase 3 inhibitors (PDE3i) are being used with increasing frequency, despite limited supporting evidence.Methods and resultsWe performed a systematic review to assess the clinical importance of PDE3i in CS. The search included studies that compared the effect of 'PDE3i with or without inotropes' with 'No PDE3i with or without inotropes' in patients with cardiogenic shock. Early death, cardiac arrest, and initiation of renal replacement therapy were assessed as outcomes. We identified 2 randomized controlled trials (RCT) with a total of 224 patients who met the eligibility requirements from the PubMed, Web of Science, and CENTRAL databases, up until October 31, 2024. One RCT compared milrinone with dobutamine (DOB), and another compared enoximone with levosimendan. Meta-analysis revealed that PDE3i were neither superior nor inferior for the outcomes in the total cohort (odds ratio [OR] 1.47, 95% confidence interval [CI] 0.35-6.26 for early deaths; OR 1.14, 95% CI 0.42-3.14 for cardiac arrest; OR 1.53, 95% CI 0.80-2.92 for the initiation of renal replacement therapy).ConclusionsThe present systematic review revealed no difference in outcomes, early deaths, cardiac arrest and initiation of renal replacement therapy when using PDE3i in patients with CS treated with or without other inotropes.

Abstract licence: CC BY-NC-ND

Cyclic nucleotide phosphodiesterases (PDEs) modulate the neurohormonal regulation of cardiac function by degrading cAMP and cGMP. In cardiomyocytes, multiple PDE isozymes with different enzymatic properties and subcellular localization regulate local pools of cyclic nucleotides and specific functions. This organization is heavily perturbed during cardiac hypertrophy and heart failure (HF), which can contribute to disease progression. Clinically, PDE inhibition has been considered a promising approach to compensate for the catecholamine desensitization that accompanies HF. Although PDE3 inhibitors, such as milrinone or enoximone, have been used clinically to improve systolic function and alleviate the symptoms of acute HF, their chronic use has proved to be detrimental. Other PDEs, such as PDE1, PDE2, PDE4, PDE5, PDE9 and PDE10, have emerged as new potential targets to treat HF, each having a unique role in local cyclic nucleotide signalling pathways. In this Review, we describe cAMP and cGMP signalling in cardiomyocytes and present the various PDE families expressed in the heart as well as their modifications in pathological cardiac hypertrophy and HF. We also appraise the evidence from preclinical models as well as clinical data pointing to the use of inhibitors or activators of specific PDEs that could have therapeutic potential in HF.

Abstract licence: CC BY