Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear. AIMS: We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients. CONCLUSION: While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.

Safety and efficacy of direct oral anticoagulants in comparison with warfarin across different BMI ranges: A systematic review and meta-analysis.

Background: Many publications have compared various outcomes defining safety and efficacy of DOACs across different BMI ranges. Our meta-analysis compares warfarin and DOACs for its treatment effects over different BMI ranges. Methods: A systematic search was conducted from inception to May 2021 on PubMed, Scopus and Embase databases. The data was extracted and pooled using a random effects model. Our study consisted of patients being treated for VTE and AF, across different BMI categories. For the comparison of DOAC, risk ratios (RR) with 95% confidence intervals (CIs) were used, whilst for the second comparison between warfarin and DOACs odds ratios (OR) were used. Results: In our first comparison, 12 studies (n = 254,908 patients) were included. For our second comparison, six studies (n = 109,609 patients) were included. Major bleeding events in the underweight group were higher than normal weight [RR: 1.89 (1.10, 3.23); P = 0.02; I 2  = 0%]. Overweight patients were related with reduced rates of VTE than in patients with normal BMI [RR: 0.86 (0.76, 0.97); P = 0.02; I 2  = 0%]. In comparison with patients receiving warfarin, DOACs had significantly reduced risk of major bleeding in normal weight, overweight and obese [OR: 0.64 (0.49, 0.83); P = 0.0007 I 2  = 90%]. Conclusion: The risk of VTE reduces with an increasing BMI, hence there could be a possible obesity paradox in patients with anticoagulation therapy. In comparison to warfarin, DOACs proved to be the safer option by having a reduced risk of bleeding across all BMI categories.