Meta-analysis evaluating apixaban in patients with atrial fibrillation and end-stage renal disease requiring dialysis.

Background: Warfarin is considered the primary oral anticoagulant for patients with atrial fibrillation and end-stage renal disease (ESRD) requiring dialysis. Although warfarin can offer significant stroke prevention in this population, the accompanying major bleeding risks make warfarin nearly prohibitive. Apixaban was shown to be superior to warfarin in preventing stroke or systemic embolism, with a lower risk of bleeding and mortality in a large, randomized trial of individuals with mostly normal renal function but none with ESRD. Methods: We systematically reviewed evidence comparing apixaban versus warfarin for atrial fibrillation in this population, and evaluated outcomes of stroke or systemic embolism, and major bleeding using random-effects models. The main safety outcome was major bleeding, and the main effectiveness outcome was stroke or systemic embolism. Results: We found five observational studies of 10 036 patients (2638 receiving apixaban, and 7398 receiving warfarin) meeting inclusion criteria. Pooled analysis demonstrated a significant reduction in major bleeding with apixaban as compared to warfarin (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.42-0.61; p < .0001). Apixaban was also associated with a reduction in intracranial bleeding (OR 0.58, 95% CI 0.37-0.92; p = .02) and in gastrointestinal bleeding (OR 0.61, 95% CI 0.51-0.73; p < .0001). Furthermore, apixaban was associated with a reduction in stroke/systemic embolism (OR 0.64, 95% CI 0.50-0.82; p < .0001). Conclusion: Apixaban was associated with superior outcomes and reduced adverse events compared to warfarin in observational studies of patients with atrial fibrillation on dialysis. Randomized controlled studies are needed to confirm these findings.

Major Adverse Cardiovascular Events Associated With Postoperative Atrial Fibrillation After Noncardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent occurrence after noncardiac surgery. It remains unclear whether POAF is associated with an increased risk of major adverse events. We aimed to elucidate the risk of stroke, myocardial infarction, and death associated with POAF following noncardiac surgery by a meta-analysis of randomized controlled studies and observational studies. METHODS: We searched electronic databases from inception up to August 1, 2019 for all studies that reported stroke or myocardial infarction in adult patients who developed POAF following noncardiac surgery. We used random-effects models to summarize the studies. RESULTS: The final analyses included 28 studies enrolling 2 612 816 patients. At 1-month (10 studies), POAF was associated with an ≈3-fold increase in the risk of stroke (weighted mean 2.1% versus 0.7%; odds ratio [OR], 2.82 [95% CI, 2.15-3.70]; P<0.001). POAF was associated with ≈4-fold increase in the long-term risk of stroke with (weighted mean, 2.0% versus 0.6%; OR, 4.12 [95% CI, 3.32-5.11]; P≤0.001) in 8 studies with ≥12-month follow-up. There was a significant overall increase in the risk of stroke and myocardial infarction associated with POAF (weighted mean, 2.5% versus 0.9%; OR, 3.44 [95% CI, 2.38-4.98]; P<0.001) and (weighted mean, 12.6% versus 2.7%; OR, 4.02 [95% CI, 3.08-5.24]; P<0.001), respectively. Furthermore, POAF was associated with a 3-fold increase in all-cause mortality at 30 days (weighted mean, 15.0% versus 5.4%; OR, 3.36 [95% CI, 2.13-5.31]; P<0.001). CONCLUSIONS: POAF was associated with markedly higher risk of stroke, myocardial infarction, and all-cause mortality following noncardiac surgery. Future studies are needed to evaluate the impact of optimal cardiovascular pharmacotherapies to prevent POAF and to decrease the risk of major adverse events in these high-risk patients.

The association between atrial fibrillation and Alzheimer's disease: fact or fallacy? A systematic review and meta-analysis.

BACKGROUND: The association between atrial fibrillation and dementia has been described. Whether a specific association exists between atrial fibrillation and Alzheimer's disease remains uncertain. This study aims to assess the association between atrial fibrillation and Alzheimer's disease through a systematic review and meta-analysis of the literature. METHODS: An exhaustive search of electronic databases up to October 2018 was conducted. Studies that identified patients with and without atrial fibrillation as well as patients with and without Alzheimer's disease and reported results of at least one relevant outcome, including hazard ratio of the association between atrial fibrillation and Alzheimer's disease were included in this analysis. The hazard ratios and their confidence interval were then pooled using a DerSimonian and Laird random effects model. RESULTS: Six studies enrolling a total of 56 370 patients were included. At baseline, the mean or median ages ranged from 50 to 78 years with a subsequent follow-up of 3 to 25 years. The random-effect pooled analysis showed a hazard ratio of 1.30 (95% confidence interval 1.01-1.59) and the heterogeneity was not significant, I 48.1%. All of the included studies were rated as good quality. CONCLUSION: Pooled analysis suggest that patients with atrial fibrillation may be exposed to an increased risk of developing new onset of Alzheimer's disease. Given the relevant clinical implications, further studies are required to corroborate these findings.

The Role of Cardiovascular and Metabolic Comorbidities in the Link between Atrial Fibrillation and Cognitive Impairment: An Appraisal of Current Scientific Evidence.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice with implications on long-term outcomes. Metabolic disorders including diabetes mellitus and obesity are independent predictors of atrial fibrillation and present therapeutic targets to reduce both the incidence and duration burden of atrial fibrillation. The presence of pericardial fat in direct contact with cardiac structures, as well the subsequent release of proinflammatory cytokines, may play an important role in this connection. Atrial fibrillation is an independent predictor of cognitive impairment and dementia. While clinical stroke is a major contributor, other factors such as cerebral hypoperfusion and microbleeds play important roles. New evidence suggests that atrial fibrillation and cognitive impairment may be downstream events of atrial cardiomyopathy, which may be caused by several factors including metabolic syndrome, obesity, and obstructive sleep apnea. The mechanisms linking these comorbidities to cognitive impairment are not yet fully elucidated. A clearer understanding of the association of AF with dementia and cognitive impairment is imperative. Future studies should focus on the predictors of cognitive impairment among those with AF and aim to understand the potential mechanisms underlying these associations. This would inform strategies for the management of AF aiming to prevent continued cognitive impairment.

Meta-analysis of Randomized Controlled Trials Assessing the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies on Mortality and Cardiovascular Outcomes.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by monoclonal antibodies has been shown to reduce low density lipoprotein (LDL-C) but its effects on cardiovascular (CV) outcomes have not been fully described. The aim of this study is to assess the impact of PCSK9 inhibition on mortality and CV outcomes by pooling data from all available randomized clinical trials (RCT) of PCSK9 inhibitors. We conducted a comprehensive search of electronic databases, up to December 1, 2018, for all RCTs comparing PCSK9 inhibition to placebo or ezetimibe in patients with hypercholesterolemia or coronary artery disease receiving maximally tolerated statin for primary or secondary prevention of mortality and cardiovascular outcomes. We used random-effects meta-analyses to summarize the studies. We retained 23 RCTs having included 88,041 patients in primary and secondary prevention. The follow-up ranged from 6 to 36 months. PCSK9 inhibition was not significantly associated with reductions in total mortality (odds ratio [OR] 0.91, 95% confidence interval [CI] 078 to 1.06; p = 0.22) and CV mortality (OR 0.95, 95% CI 0.84 to 1.07; p = 0.37). In contrast, PCSK9 inhibition was associated with reductions in myocardial infarction (OR 0.80, 95% CI 0.71 to 0.91; p <0.0001), stroke (OR 0.75, 95% CI 0.65 to 0.85; p <0.0001), and coronary revascularization (OR 0.82, 95% CI 0.77 to 0.88; p <0.0001). In conclusion, PCSK9 inhibition was associated with reductions in myocardial infarction, stroke, and coronary revascularization. Future analyses may identify high-risk patients who may benefit more from these agents and longer follow-up of current or new trials may show a mortality benefit.

Subclinical Atrial Fibrillation and Risk of Stroke: Past, Present and Future.

Subclinical atrial fibrillation (SCAF) describes asymptomatic episodes of atrial fibrillation (AF) that are detected by cardiac implantable electronic devices (CIED). The increased utilization of CIEDs renders our understanding of SCAF important to clinical practice. Furthermore, 20% of AF present initially as a stroke event and prolonged cardiac monitoring of stroke patients is likely to uncover a significant prevalence of SCAF. New evidence has shown that implanting cardiac monitors into patients with no history of atrial fibrillation but with risk factors for stroke will yield an incidence of SCAF approaching 30-40% at around three years. Atrial high rate episodes lasting longer than five minutes are likely to represent SCAF. SCAF has been associated with an increased risk of stroke that is particularly significant when episodes of SCAF are greater than 23 h in duration. Longer episodes of SCAF are incrementally more likely to progress to episodes of SCAF >23 h as time progresses. While only around 30-40% of SCAF events are temporally related to stroke events, the presence of SCAF likely represents an important risk marker for stroke. Ongoing trials of anticoagulation in patients with SCAF durations less than 24 h will inform clinical practice and are highly anticipated. Further studies are needed to clarify the association between SCAF and clinical outcomes as well as the factors that modify this association.