Demographics and mortality trends of valvular heart disease in older adults in the United States: Insights from CDC-wonder database 1999-2019.

Background: Valvular heart disease (VHD) represents a spectrum of cardiac conditions, including valvular stenosis, valvular regurgitation, or mixed lesions affecting single or multiple valves. The severity of VHD has emerged as a major cause of cardiovascular (CV) morbidity and mortality among the older population in the United States (U.S). Objective: To evaluate temporal trends in mortality associated with VHD in the elderly U.S population between 1999 and 2019. Methods: We utilized the CDC WONDER database for VHD mortality in adults ≥75 from 1999 to 2019, using ICD-10 codes. Age-adjusted mortality rates (AAMR) per 100,000 people with associated annual percentage change (APC) were calculated. Joinpoint regression was used to assess the overall trends and trends for demographic, geographic, and type of valvular disease subgroups. Results: A total of 666,765 VHD deaths in older adults from 1999 to 2019 was identified, with an initial decline in AAMR until 2007 with an APC: 0.62, 95 % CI (-1.66-0.33), stability until 2014, and a significant decrease until 2019 (APC: 1.47, 95 % CI [-2.24-1.04], P < 0.0001). Men consistently had higher AAMRs compared to women (overall AAMR men: 173.6; women: 138.2). The AAMRs were found to be highest in the White (166.5), followed by American Indian or Alaska Native population at (93.8) Hispanic or Latino at (80.7), Black or African American populations at (74.1) and lastly Asian or Pacific Islander (73.4). Non-metropolitan areas manifested higher AAMRs for deaths related to VHD than metropolitan areas (overall AAMRs 160.5 vs 149.5) respectively. State-wide AAMRs varied, with the highest in Vermont at 324.2 (95 % CI [313.0-335.4], P < 0.0001) and the lowest in Mississippi at 88.0 (95 % CI [85.0-91.0], P < 0.0001). Non-rheumatic and aortic valve disorders in adults ≥75 years had higher mortality rates compared to rheumatic or mitral valve conditions in those <75 years. Conclusion: Our study showed a decline in U.S. VHD mortality from 1999 to 2019 but found persistent disparities by gender, race, age, region, and VHD type. Targeted policies for prevention and early diagnosis are needed to address these inequalities.

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Efficacy of oral anticoagulants in chronic kidney disease and hemodialysis patients with atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION: This meta-analysis seeks to evaluate the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in individuals with chronic kidney disease (CKD), end-stage renal disease (ESRD), and undergoing hemodialysis (HD) who also have atrial fibrillation (AF). EVIDENCE ACQUISITION: A comprehensive search of MEDLINE, clinicaltrials.gov, EMBASE, and Cochrane Database for relevant studies reporting the usefulness of OAC therapy for CKD, ESRD, and HD patients with AF was conducted from its inception until 1st May 2023. The studies that reported OR, RR, or HR for adult AF patients to investigate the efficacy of OAC in CKD, ESRD, and HD were included. Statistical analysis was completed using a generic inverse variance and random-effects model to calculate the combined HR and their corresponding 95% CIs for all outcomes. EVIDENCE SYNTHESIS: The meta-analysis included 33 studies with 178,956 patients. The analysis revealed that the DOACs, when compared to VKA, significantly lowered the risk of stroke or systemic embolism (HR: 0.81 [95% CI: 0.70, 0.93]; P=0.002; I2=62%), bleeding (HR: 0.77, [95% CI: 0.67, 0.89]; P=0.0003; I2=83%), and intracranial hemorrhage (HR: 0.56, [95% CI 0.47, 0.66]; P<0.00001; I2=0%). Similarly, the risks of cardiovascular death (HR: 0.88, [95% CI 0.78, 1.00]; P=0.05; I2=0%), all-cause mortality (HR: 0.88, [95% CI 0.70, 1.10]; P=0.25; I2=96%), and myocardial infarction (HR: 0.80, [95% CI 0.54, 1.17]; P= 0.25; I2= 0%) were lowered by DOAC, but the result was insignificant. No significant difference was seen in the risk of gastrointestinal bleeding between DOAC and VKA as well (HR: 0.95, [95% CI 0.75, 1.20]; P=0.65; I2=83%). CONCLUSIONS: Our meta-analysis confirms that DOACs are effective for managing AF in patients with kidney disease, with potential clinical implications for AF and CKD management. Further research should explore DOACs' reno-protective effects.

The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: A systematic review and meta-analysis.

Background: Dementia is a recognized complication of atrial fibrillation (AF). Oral anticoagulant (OAC) therapy can potentially be protective against this complication. Methods: A comprehensive search of MEDLINE and Embase for comparative observational studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. Studies that had patients with prior use of OAC or with a previous history of dementia were excluded. Results: A total of 22 studies were included in this review involving 617,204 participants. The pooled analysis revealed that OAC therapy, including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), was associated with a reduced incidence of dementia in AF patients. Specifically, compared to non-OAC treatment, OACs demonstrated a significant reduction in dementia incidence (HR 0.68, 95 % CI [0.58, 0.80], p < 0.00001), with similar findings observed for DOACs (HR 0.69, 95 % CI [0.51, 0.94], p = 0.02) and VKAs (HR 0.73, 95 % CI [0.56, 0.95], p = 0.02). The comparison of DOAC vs VKA revealed that DOACs are associated with reduced risk of dementia (HR 0.87, 95 % CI [0.79, 0.96], p = 0.004). Conclusion: Our SR and meta-analysis showed that the use of OAC therapy is associated with a reduced risk of dementia in individuals with AF. However, our results are limited by the potential influence of confounding bias and significant heterogeneity in the analyses.

Therapeutic Outcomes Following Isolated Transcatheter Tricuspid Valve Repair: A Systematic Review and Meta-analysis.

Tricuspid regurgitation (TR) is traditionally treated surgically, but isolated transcatheter tricuspid valve repair (ITTVR) offers a less invasive option. This study conducts a meta-analysis and systematic review to evaluate ITTVR outcomes in patients with TR. Database searches until March 2023 identified studies assessing ITTVR safety and efficacy in moderate/severe TR patients. Primary outcomes analyzed were severe TR, NYHA functional class improvement, and 6-minute walking distance. Meta-analyses used Risk ratio (RR) or mean difference with a random effects model. The review included 25 studies with 2421 patients. ITTVR improved NYHA functional class (RR: 3.262), reduced TR severity (RR: 0.303), and enhanced 6-minute walking distance (MD: +47.077 m). Echocardiographic parameters improved, including reductions in TR vena contracta, TR EROA, septolateral tricuspid annular diameter, RVEDD, RV FAC, and TAPSE. LVEF and PASP showed no significant changes. ITTVR improves functional outcomes and echocardiographic parameters in TR patients.