Stroke and Bleeding in Atrial Fibrillation with Chronic Kidney Disease

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Abstract

Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

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Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications.

W M Feinberg, J Blackshear, A Laupacis … (1995)

The prevalence of atrial fibrillation (AF) is related to age. Anticoagulation is highly effective in preventing stroke in patients with AF, but the risk of hemorrhage may be increased in older patients. We reviewed the available epidemiologic data to define the age and sex distribution of people with AF. From four large recent population-based surveys, we estimated the overall age- and gender-specific prevalence of AF. These estimates were applied to the recent US census data to calculate the number of men and women with AF in each age group. There are an estimated 2.2 million people in the United States with AF, with a median age of about 75 years. The prevalence of AF is 2.3% in people older than 40 years and 5.9% in those older than 65 years. Approximately 70% of individuals with AF are between 65 and 85 years of age. The absolute number of men and women with AF is about equal. After age 75 years, about 60% of the people with AF are women. In contrast to people with AF in the general population, patients with AF in recent anticoagulation trials had a mean age of 69 years, and only 20% were older than 75 years. The risks and benefits of antithrombotic therapy in older individuals are important considerations in stroke prevention in AF.

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Validity of Stroke Diagnoses in a National Register of Patients

Lars-Henrik Krarup, Gudrun Boysen, Huma Janjua … (2007)

Background: Many registers containing routine medical information have been developed for research and surveillance purposes. In epidemiological research assessment of endpoints is often conducted via registers. In the present study we validated stroke and transient ischemic attack (TIA) diagnoses in the Danish National Register of Patients (DNRP). Methods: Subjects from a Danish cohort study, the Copenhagen City Heart Study (n = 19,698), were crosslinked with the DNRP. The following International Classification of Disease 10th revision codes were used to identify possible strokes and TIAs: I60–I69 and G45. Two independent raters reviewed all cases. Positive predictive values of stroke, TIA and stroke subtypes were estimated by dividing the confirmed cases by the total number of cases located in the DNRP. Interrater reliability was tested using ĸ statistics. Results: Of 236 possible cerebrovascular events, 1 in 6 stroke diagnoses did not meet study criteria. The majority of events in the DNRP were registered as unspecified stroke (I64), n = 105 (44%), of which two thirds were diagnosed as ischemic stroke events by the raters. Intracerebral hemorrhage and ischemic stroke had a positive predictive value from 74 to 97%, respectively. Conclusion: Our results show that the DNRP tends to overestimate the number of cerebrovascular events, while ischemic stroke is underestimated.

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Low glomerular filtration rate and risk of stroke: meta-analysis

Meng-Luen Lee, Jeffrey L Saver, Kuo-Hsuan Chang … (2010)

Objective To qualitatively and quantitatively investigate the link between a low estimated glomerular filtration rate (eGFR) at baseline and risk of future stroke. Design Systematic review and meta-analysis of prospective studies. Data sources PubMed (1966-October 2009) and Embase (1947-October 2009). Selection criteria Inclusion criteria were studies that prospectively collected data within cohort studies or clinical trials, estimated glomerular filtration rate at baseline using the modification of diet in renal disease or Cockcroft-Gault equations, assessed incident stroke, had a follow-up of at least one year, and reported quantitative estimates of multivariate adjusted relative risk and 95% confidence interval for stroke associated with an eGFR of 60-90 ml/min/1.73 m2 or <60 ml/min/1.73 m2. Data abstraction Two investigators independently abstracted data from eligible studies. Estimates were combined using a random effects model. Heterogeneity was assessed by P value of χ2 statistics and I2. Publication bias was assessed by visual examination of funnel plots. Results 21 articles derived from 33 prospective studies: 14 articles assessed eGFR <60 ml/min/1.73 m2 and seven assessed eGRF at both <60 ml/min/1.73 m2 and 60-90 ml/min/1.73 m2 for a total of 284 672 participants (follow-up 3.2-15 years) with 7863 stroke events. Incident stroke risk increased among participants with an eGFR <60 ml/min/1.73 m2 (relative risk 1.43, 95% confidence interval 1.31 to 1.57; P<0.001) but not among those with an eGFR of 60-90 ml/min/1.73 m2 (1.07, 0.98 to 1.17; P=0.15). Significant heterogeneity existed between estimates among patients with an eGFR <60 ml/min/1.73 m2 (P<0.001). In subgroup analyses among participants with an eGFR <60 ml/min/1.73 m2, heterogeneity was significant in Asians compared with non-Asians (1.96, 1.73 to 2.23 v 1.25, 1.16 to 1.35; P<0.001), and those with an eGFR of 40-60 ml/min/1.73 m2 v <40 ml/min/1.73 m2 (1.28, 1.04 to 1.56 v 1.77, 1.32 to 2.38; P<0.01). Conclusions A baseline eGFR <60 ml/min/1.73 m2 was independently related to incident stroke across a variety of participants and study designs. Prompt and appropriate implementation of established strategies for reduction of vascular risk in people with know renal insufficiency may prevent future strokes.