Sildenafil for congenital heart diseases induced pulmonary hypertension, a meta-analysis of randomized controlled trials.

Abstract

Background: PDE5 inhibitors (PDE5-Is) manifest its effects by inhibiting the PDE5 dependent cGMP hydrolysis, thus increasing cGMP intracellularly which results in vascular smooth muscles relaxation and vasodilatation. PDE 5 inhibitors, such as sildenafil, were first prescribed for angina pectoris then for erectile dysfunction (ED). Recently, sildenafil has been proposed in congenital heart diseases (CHD) induced PAH, which constitute a huge burden on children health and can attribute to fatal complications due to the un-oxygenated blood presents in the systemic circulation. Therefore, our meta-analysis aims to further investigate the safety and efficacy of sildenafil in CHD induced PH. Methods: We searched the following electronic databases: PubMed, Cochrane CENTRAL, WOS, Embase, and Scopus from inception to April 20th, 2022. Randomized controlled trials that assess the efficacy of using sildenafil in comparison to placebo or any other vasodilator drug were eligible for inclusion. The inverse variance method was used to pool study effect estimates using random effect model. Effect sizes are provided in the form of mean difference (MD) with 95% confidence intervals (CI). Results: Our study included 14 studies with (n = 849 children) with a mean age of 7.9 months old. Sildenafil showed statistically significant decrease over placebo in mPAP and sPAP with MD -7.42 (95%CI [-13.13, -1.71], P = 0.01) and − 8.02 (95%CI [-11.16, -4.88], P < 0.0001), respectively. Sildenafil revealed a decrease in mAOP and PA/OA ratio over placebo with MD -0.34 (95%CI [-2.42, 1.73], P = 0.75) and MD -0.10 (95%CI [-0.11, -0.09], P < 0.00001), respectively. Regarding post-operative parameters, sildenafil had a statistically significant lower mechanical ventilation time, ICU stay, and hospital stay over placebo with MD -19.43 (95%CI [-31.04, -7.81], P = 0.001), MD -34.85 (95%CI [-50.84, -18.87], P < 0.00001), and MD -41.87 (95%CI [-79.41, -4.33], P = 0.03), respectively. Nevertheless, no difference in mortality rates between sildenafil and placebo with OR 0.25 (95%CI 0.05, 1.30], P = 0.10) or tadalafil with OR 1 (95%CI 0.06, 17.12], P = 1). Conclusion: Sildenafil is a well-tolerated treatment in congenital heart diseases induced pulmonary hypertension, as it has proven its efficacy not only in lowering the mPAP and sPAP, but also in reducing the ventilation time, ICU and hospital stay with no difference observed regarding mortality rates.

Are congenital heart defects connected to more severe attention-deficit/hyperactivity disorder?: A systematic review and meta-analysis

“…Recent improvements in medical treatments, surgical procedures, imaging, and pediatric intensive care helped more than 90% of congenital heart disease (CHD) children reach adulthood and decreased the total mortality rate by 31%in the previous 20 years. [2,3] This changes our focus on CHD from mortality to morbidity, where although babies born with CHD now have a longer life expectancy and better quality of life, they are more likely to have psychological distress, neurocognitive deficits, and social challenge. Studies reported that approximately 30% had mood or anxiety disorders and 20% showed symptoms comparable with posttraumatic stress disorder.…”