Rivaroxaban versus warfarin in patients with atrial fibrillation enrolled in Latin America: Insights from ROCKET AF.

BACKGROUND: ROCKET AF demonstrated the efficacy and safety of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). We examined baseline characteristics and outcomes in patients enrolled in Latin America compared with the rest of the world (ROW). METHODS: ROCKET AF enrolled 14,264 patients from 45 countries. Of these, 1,878 (13.2%) were from 7 Latin American countries. The clinical characteristics and outcomes (adjusted by baseline characteristics) of these patients were compared with 12,293 patients from the ROW. Treatment outcomes of rivaroxaban compared with warfarin were also stratified by region. RESULTS: The annual rate of stroke/SE was similar in those from Latin American and ROW (P= .63), but all-cause and vascular death were significantly higher than in ROW (HR 1.40, 95% CI 1.20-1.64; HR 1.38, 95% CI 1.14-1.68; P< .001). Rates of major or nonmajor clinically relevant bleeding tended to be lower in Latin America (HR 0.89, 95% CI 0.80-1.0; P= .05). Rates of stroke and/or SE were similar with rivaroxaban and warfarin in patients from Latin America and ROW (HR 0.83, 95% CI 0.54-1.29 vs HR 0.89, 95% CI 0.75-1.07; interaction P= .77). CONCLUSIONS: Patients with AF in Latin America had similar rates of stroke and/or SE, higher rates of vascular death, and lower rates of bleeding compared with patients in the ROW. The effect of rivaroxaban compared with warfarin in Latin America was similar to the ROW. Further studies analyzing patient- and country-specific determinants of these regional differences in Latin America are warranted.

Meta-analysis of the efficacy and safety of non-vitamin K antagonist oral anticoagulants with warfarin in Latin American patients with atrial fibrillation.

BACKGROUND: Data of non-vitamin K antagonist oral anticoagulants (NOACs) in current management of atrial fibrillation (AF) are predominantly derived from North American and European regions. However, the effects of NOACs for stroke prevention in Latin America remain unclear. Therefore, we aimed to compare the efficacy and safety of NOACs with warfarin in Latin American patients with AF. METHODS: The PubMed and Embase databases were systematically searched until July 12, 2019 for applicable randomized clinical trials. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS: Four trials involving 8943 Latin American patients were included in this meta-analysis. In anticoagulated patients with AF, Latin American patients had higher rates of stroke or systemic embolism and all-cause death compared with non-Latin American subjects. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism, major bleeding, intracranial bleeding, and any bleeding in Latin American patients. There were no significant differences in the risks of ischemic stroke, all-cause death, and gastrointestinal bleeding between Latin and non-Latin American groups. All the interactions between Latin and non-Latin American groups about efficacy and safety outcomes of NOACs compared with warfarin were non-significant (all Pinteraction > .05). CONCLUSIONS: Our meta-analysis suggested that the use of NOACs was at least non-inferior to warfarin use for stroke prevention in Latin American patients with AF.

Prevalence and Associations of Retinal Emboli With Ethnicity, Stroke, and Renal Disease in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Disease Study.

Importance: To our knowledge, population-based data on retinal emboli are limited in Asia. Besides its associations with traditional cardiovascular risk factors and stroke, associations between retinal emboli and renal disease and function remain unclear. Objective: To examine the prevalence of and risk factors for retinal emboli in a large, contemporary, multiethnic Asian population. Design, Setting, and Participants: This population-based cross-sectional study was conducted from 2004 to 2011 and included a total of 10 033 Chinese, Malay, and Indian persons aged 40 to 80 years residing in the general communities of Singapore. Analyses were performed from November 2016 to February 2017. Interventions or Exposures: Retinal emboli were ascertained from retinal photographs obtained from both eyes of all participants according to a standardized protocol. Age-standardized prevalence of retinal emboli was calculated using the 2010 Singapore adult population. Risk factors were assessed from comprehensive systemic and ophthalmic examinations, interviews, and laboratory investigations. Main Outcomes and Measures: Retinal emboli. Results: Of the 10 033 participants, 9978 (99.5%) had gradable retinal photographs. Of these, 5057 (50.7%) were female, and 3375 (33.8%) were Indian. We identified 88 individuals (0.9%) with retinal emboli; the overall person-specific, age-standardized prevalence of retinal emboli was 0.75% (95% CI, 0.60-0.95), with the highest prevalence seen in the Indian cohort (0.98%), followed by the Chinese (0.73%) and Malay (0.44%) cohorts (P = .03). In multivariable-adjusted analysis, factors associated with prevalent retinal emboli included older age (per 5-year increase; odds ratio [OR], 1.22; 95% CI, 1.05-1.41), Indian ethnicity (compared with Malay ethnicity; OR, 3.58; 95% CI, 1.95-6.60), hypertension (OR, 1.95; 95% CI, 1.03-3.70), chronic kidney disease (OR, 2.05; 95% CI, 1.15-3.64), creatinine level (per SD increase; OR, 1.13; 95% CI, 1.05-1.21), glomerular filtration rate (per SD increase; OR, 0.67; 95% CI, 0.51-0.86), and history of stroke (OR, 3.45; 95% CI, 1.70-6.99). Conclusions and Relevance: Based on 88 individuals among 9978 participants of 3 major Asian ethnic populations, retinal emboli were most commonly seen in Indian persons and associated with conventional cardiovascular risk factors, stroke, and chronic kidney disease. Therefore, its presence may signal vascular embolic event and damage not only in the brain but also in the kidneys. If these data are confirmed in longitudinal studies, they would suggest that persons with retinal emboli may require both general cardiovascular and renal assessment.

Racial/ethnic differences in atrial fibrillation symptoms, treatment patterns, and outcomes: Insights from Outcomes Registry for Better Informed Treatment for Atrial Fibrillation Registry.

BACKGROUND: Significant racial/ethnic differences exist in the incidence of atrial fibrillation (AF). However, less is known about racial/ethnic differences in quality of life (QoL), treatment, and outcomes associated with AF. METHODS: Using data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we compared clinical characteristics, QoL, management strategies, and long-term outcomes associated with AF among various racial/ethnic groups. RESULTS: We analyzed 9,542 participants with AF (mean age 74 ± 11 years, 43% women, 91% white, 5% black, 4% Hispanic) from 174 centers. Compared with AF patients identified as white race, patients identified as Hispanic ethnicity and those identified as black race were younger, were more often women, and had more cardiac and noncardiac comorbidities. Black patients were more symptomatic with worse QoL and were less likely to be treated with a rhythm control strategy than other racial/ethnic groups. There were no significant racial/ethnic differences in CHA2DS2-VASc stroke or ATRIA bleeding risk scores and rates of oral anticoagulation use were similar. However, racial and ethnic minority populations treated with warfarin spent a lower median time in therapeutic range of international normalized ratio (59% blacks vs 68% whites vs 62% Hispanics, P < .0001). There was no difference in long-term outcomes associated with AF between the 3 groups at a median follow-up of 2.1 years. CONCLUSION: Relative to white and Hispanic patients, black patients with AF had more symptoms, were less likely to receive rhythm control interventions, and had lower quality of warfarin management. Despite these differences, clinical events at 2 years were similar by race and ethnicity.

The impact of VKORC1-1639G > A genetic polymorphism upon warfarin dose requirement in different ethnic populations.

OBJECTIVE: Published data on the association between vitamin K epoxide reductase complex 1 (VKORC1)-1639G > A polymorphism and warfarin dose requirement are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS AND RESULTS: Studies were identified in English-language articles by search of PubMed and Embase database (inception to July 2013). A total of 32 prospective clinical trials involving 5005 patients were identified and included for analysis. Overall, the weighted mean maintenance dosage of warfarin in patients with the -1639AA genotype decreased 2.62 mg/d compared with that in the -1639GG genotype patients (95% CI -3.10 to -2.14; P < 0.00001) when 24 eligible studies were pooled into the meta-analysis. Furthermore, significantly lower warfarin dose requirement was found in patients with GA genotype versus GG genotype (WMD, -1.32; 95% CI -1.67 to -0.96; P < 0.00001). In the subgroup analysis by ethnicity, statistically significant lower maintenance dosage of warfarin in patients with the AA genotype versus GG genotype were found in both Caucasians (WMD, -2.47; 95% CI -2.92 to -2.03; P < 0.00001) and Asians (WMD, -2.84; 95% CI -4.57 to -1.11; P = 0.001). CONCLUSIONS: This meta-analysis indicated that the VKORC1-1639G > A genetic polymorphism is associated with the variation of interindividual warfarin dose requirement in different ethnic populations.

Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in Chinese patients with atrial fibrillation.

This study assessed the effects and safety of rivaroxaban versus warfarin in Chinese patients with atrial fibrillation. In this double-blind clinical trial, a total of 353 consecutive patients with atrial fibrillation who were at risk of stroke or systemic embolism were enrolled to receive either rivaroxaban or warfarin. The primary effect endpoint occurred in five patients in the rivaroxaban group (2.29% per year) and in seven patients in the warfarin group (2.91% per year) (hazard ratio with warfarin, 0.76, 95% CI, 0.64-0.91; p = 0.03). Major and non-major clinically relevant bleeding occurred in 38 patients (14.3% per year) in the rivaroxaban group and in 36 patients (13.7% per year) in the warfarin group (hazard ratio rivaroxaban versus warfarin, 1.07; 95% CI, 0.93-1.14; p = 0.39). Adverse events were similar between these two arms (p > 0.05). In conclusion, oral administration of rivaroxaban reduced the risk of stroke or systemic embolism without significantly increasing the safety concern.

Enhanced prothrombin formation and platelet activation in Chinese patients after transcatheter closure of atrial septal defect.

BACKGROUND: The objective of this study was to investigate changes in coagulation activation and platelet activation after transcatheter closure of atrial septal defect (ASD) by determining the levels of specific markers over time to provide insight into preventing postprocedural embolism. HYPOTHESIS: We hypothesis that the activation status of coagulation and the platelet would be changed after the closure of ASD. METHODS: Forty consecutive patients who underwent transcatheter closure of ASD with the Lifetech ASD occluder (Lifetech Scientific, Shenzhen, China) were included in this prospective study. The serum level of prothrombin fragment 1 + 2 (F1 + 2) and expressions of P-selectin (CD62P) and platelet glycoprotein IIb/IIIa receptor (CD41a) on the surface of platelets were evaluated at baseline and at 1 day, 1 month, and 3 months after the closure. RESULTS: The median F1 + 2 level was 0.96 nmol/L. This increased to a maximal value of 1.43 nmol/L at 1 day after closure, but gradually returned to the baseline level at 1 month after closure and remained there at 3 months after closure (medians were 0.98 nmol/L and 1.08 nmol/L, respectively). Platelet surface expression of CD62P and CD41a decreased at 1 day, 1 month, and 3 months after closure. For CD62P, average expressions were 8.21% +/- 2.11%, 6.28% +/- 1.72%, 5.29% +/- 1.52%, and 4.41% +/- 1.11%, respectively, for baseline and 1 day, 1 month, and 3 months after closure. For CD41a, average expressions were 79.37% +/- 14.14%, 71.98% +/- 13.77, 56.69% +/- 13.05%, and 54.88% +/- 11.62%, respectively. CONCLUSIONS: Transcatheter closure of ASD with the Lifetech ASD occluder was associated with significantly increased coagulation activation and decreased platelet activation. No evidence supporting the use of aspirin to prevent thrombus formation after closure was found.

Prevalence and risk factors of retinal arteriolar emboli: the Singapore Malay Eye Study.

PURPOSE: To examine the prevalence and risk factors of retinal arteriolar emboli, a risk predictor of stroke, in an Asian population. DESIGN: Population-based cross-sectional study. METHODS: Retinal emboli were ascertained from retinal photographs obtained from both eyes of 3,265 Asian Malays, aged 40 to 80 years, according to a standardized protocol. Risk factors were assessed from detailed standardized interviews, clinical examinations, and laboratory investigations. RESULTS: The overall prevalence of retinal emboli was 0.6% (95% confidence interval [CI], 0.58 to 0.62). A finding of retinal emboli was strongly associated with increasing age (P = .005, for trend), but age-stratified prevalence rates were still lower than those reported from previous population-based studies of White persons. After adjusting for age and gender, the presence of retinal emboli was associated with cigarette smoking (odds ratio [OR], 5.96; 95% CI, 1.75 to 20.32), elevated total cholesterol (OR, 5.21; 95% CI, 1.93 to 12.82), low-density lipoprotein cholesterol (OR, 2.98; 95% CI, 1.20 to 7.39), and self-reported history of angina (OR, 5.67; 95% CI, 1.62 to 19.91). These associations remained significant in multivariate analysis with additional adjustment for other risk factors. CONCLUSIONS: Retinal emboli are less common in Asians than in similarly aged White persons, but are associated with similar cardiovascular risk factors.

Prevalence and associations of asymptomatic retinal emboli in Latinos: the Los Angeles Latino Eye Study (LALES).

PURPOSE: To study the prevalence and associations of asymptomatic retinal emboli in a cohort of Latinos and to compare these findings with those of previous population studies. DESIGN: Population-based cross-sectional study. METHODS: All participants in this study underwent a comprehensive eye examination, including fundus photography. Photographs were graded by trained masked graders. Lifestyle factors and medical history were obtained during extensive interviews. Blood pressure, serum glucose, and glycosylated hemoglobin were measured. Age- and gender-specific prevalence rates were calculated. Odds ratios (ORs) were calculated using stepwise logistic regression analyses to identify independent risk factor associated with asymptomatic retinal emboli. RESULTS: Photographs gradable for retinal emboli were obtained from 5,959 participants. For all participants, the prevalence of definite asymptomatic retinal emboli was 0.4% (n = 26). Stepwise logistic regression analyses identified smoking (> five pack years; OR, 4.3) and history of coronary artery disease (OR, 2.8) to be associated independently with retinal emboli (P < .05). CONCLUSIONS: We found a lower prevalence of asymptomatic retinal emboli compared with previous population-based studies. This could be secondary to the Los Angeles Latino Eye Study (LALES) population being younger, having lower blood pressure, and having fewer smokers than other studies. As in other studies, smoking emerges as the strongest association with retinal emboli.