Anti-atherosclerotic effect of incretin mimetics: a meta-analysis of randomized controlled trials

Background: Diabetes is a very common cause of cardiovascular disease, and metformin remains the first-line treatment of diabetes. Many trials were conducted to prove the efficacy and safety of other antidiabetic medication as the best add-on medication. Objectives: We aimed to evaluate the atherosclerotic effect of incretin mimetics in patients with diabetes.Methods: We searched in PubMed, clinicaltrials.gov and Cochrane Library for randomized controlled trials (RCTs) comparing incretin mimetic with conventional treatment. The primary outcome was the change in carotid intima-media thickness (CIMT) at the end of the trials.Results: Five RCTs (n = 1241), the mean age of patients included in the trials is 64.3 ± 11.4. The primary outcome was statistically significant for CIMT improvement in terms of long-term follow-up analysis between the incretin mimetic group and conventional group (mean difference [MD] −0.031; 95% Confidence interval [CI] −0.049 to 0.012; P = 0.001), whereas at short-term follow-up it wasn’t (MD −0.004; 95% CI −0.024 to 0.016; P = 0.7) in the overall group of study participants. Additionally, the mean change in body mass index (BMI) (MD 0.064; 95% CI −0.54 to 0.67; P = 0.8), and mean change in systolic blood pressure (MD −0.42; 95% CI −3.2 to 2.3; P = 0.8) or diastolic blood pressure (MD 0.25; 95% CI −1.18 to 1.68; P = 0.7) were not significant.Conclusion: Long-term use of incretin mimetic medication results in significant improvement of atherosclerosis, which leads to fewer vascular events, with no apparent effect on blood pressure or BMI. Further dedicated trials are required to show the superiority of adding these medications to conventional treatment versus placebo

Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis

Abstract Objectives Intravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes. Design Meta-analysis and systematic review of randomized clinical trials (RCTs). Methods and data source Electronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT). Results Six RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85–1.01; P = 0.09; I 2 = 0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84–1.01; P = 0.1; I 2 = 0), overall ICU mortality (OR 0.9, 95% CI 0.81–1.01, P = 0.08, I 2 = 0%), or need for new RRT (OR 0.92, 95% CI 0.67–1.28, P = 0.65, I 2 = 38%) between balanced crystalloids and isotonic saline in critically ill patients. Conclusion Balanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes

Prevalence and outcomes of p.Val142Ile <i>TTR</i> amyloidosis cardiomyopathy: a systematic review

Background: The p.Val142Ile variant, predominantly found among people of African descent, is the most common cause of variant transthyretin amyloidosis and carriers predominantly develop a cardiomyopathy (variant transthyretin amyloidosis cardiomyopathy) phenotype. Yet, there are conflicting data on the prevalence and outcomes of p.Val142Ile variant carriers. Methods: We performed a systematic review of the prevalence and outcomes of p.Val142Ile variant transthyretin amyloidosis cardiomyopathy among subjects of African descent. We found 62 relevant articles after searching the MEDLINE databases from 1980 to 2020 that reported data for ≈150 000 subjects. Results: The reported worldwide prevalence of the p.Val142Ile variant is 0.3% to 1.6% in the general population. Among people of African descent, the reported prevalence from all studies ranges from 1.1% to 9.8%, but for studies with >1000 subjects, it is 3% to 3.5%. The prevalence of the p.Val142Ile variant in a region is dependent on the reported percentage of subjects who are of African descent in that region. p.Val142Ile variant transthyretin amyloidosis cardiomyopathy typically presents in the seventh to eighth decade of life and the majority of cases reported were male, with 25% to 38% diagnosed with atrial fibrillation. It was associated with a longitudinally worse quality of life and a lower adjusted survival compared with other types of transthyretin amyloidosis cardiomyopathy.Conclusions: The p.Val142Ile variant is the most common variant of the transthyretin gene with most carriers being of African descent. The true penetrance is unknown but the p.Val142Ile variant is associated with increased rates of incident heart failure and portends a lower overall survival. Increased awareness could lead to earlier diagnosis and improved heart failure outcomes among those of African descent, which is of increasing importance given the advent of novel therapeutics for this disease.</p