Dataset Information

Association of Kidney Function With Risk of Adverse Effects of Therapies for Atrial Fibrillation.

ABSTRACT:

Introduction

Atrial fibrillation (AF) is common in chronic kidney disease (CKD) and is treated with rate control medications, antiarrhythmic medications, as well as anticoagulation and procedures, each of which have associated risks. We aimed to evaluate the association of CKD status with the risks of adverse effects after initiation of AF therapies.

Methods

This was a cohort study of community-based adults who newly initiated rate control medications, antiarrhythmic medications, warfarin, direct oral anticoagulants (DOACs) or received AF procedures in the 1 year after diagnosis of AF. Baseline estimated glomerular filtration rate (eGFR) was calculated using outpatient serum creatinine measures. Adverse effects within 1 year related to each AF therapy or within 1 month of an AF procedure were ascertained from vital sign databases, electrocardiograms (ECGs), and administrative codes. Fine-Gray hazard models were used to study the association of eGFR categories with risk of adverse effects for each AF therapy.

Results

Among 115,564 patients with incident AF, lower eGFR (vs. eGFR ≥60 ml/min per 1.73 m²) was significantly associated with higher adjusted risk of adverse effects after initiation of rate control therapies (most commonly hypotension and bradycardia) as follows: eGFR 45-59 (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.07-1.22), 30-44 (HR 1.15, 95% CI 1.06-1.25), and 15-29 (HR 1.29, 95% CI: 1.12-1.47) ml/min per 1.73 m². Lower eGFR was associated with higher adjusted risk of adverse effects (most commonly prolonged QRS and QTc intervals) after initiation of an antiarrhythmic medication (vs. eGFR >60 ml/min per 1.73 m²) as follows: eGFR 45-59 (HR 1.12, 95% CI 1.01-1.23) and eGFR<15 (HR 1.43, 95% CI 1.01-2.01) ml/min per 1.73 m².

Conclusion

There was a graded association between lower eGFR and risk of major bleeding with warfarin use, with the greatest risk among those with eGFR <15 ml/min per 1.73 m² (HR of 2.93, 95% CI 1.99-4.30). There was no association of eGFR with major bleeding in patients receiving DOACs. Rates of adverse effects within 1 month of an AF procedure were low among patients with (n = 18) and without (n = 41) CKD and was underpowered for further analyses. In conclusion, lower eGFR was associated with significantly higher risks of adverse effects after initiation of commonly used therapies to treat AF. These data may help inform the complex therapeutic decisions in patients with CKD and AF.

SUBMITTER: Bansal N

PROVIDER: S-EPMC10014389 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Kidney Function With Risk of Adverse Effects of Therapies for Atrial Fibrillation.

Bansal Nisha N Zelnick Leila R LR An Jaejin J Harrison Teresa N TN Lee Ming-Sum MS Singer Daniel E DE Sung Sue Hee SH Fan Dongjie D Go Alan S AS

Kidney international reports 20221213 3

<h4>Introduction</h4>Atrial fibrillation (AF) is common in chronic kidney disease (CKD) and is treated with rate control medications, antiarrhythmic medications, as well as anticoagulation and procedures, each of which have associated risks. We aimed to evaluate the association of CKD status with the risks of adverse effects after initiation of AF therapies.<h4>Methods</h4>This was a cohort study of community-based adults who newly initiated rate control medications, antiarrhythmic medications, ...[more]

PMID: 36938096

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Project description:ImportanceDirect oral anticoagulants (DOACs) are purported to have fewer drug-drug interactions than warfarin. However, potential interactions with coprescribed medications are still a safety concern. Verapamil hydrochloride and diltiazem hydrochloride are combined P-glycoprotein (P-gp) and CYP3A4 inhibitors and may be associated with increases in the risk of bleeding with DOACs.ObjectiveTo evaluate the risk of bleeding with DOACs and verapamil or diltiazem using an active comparator design.Design, setting, and participantsA comparative effectiveness active comparator cohort study was conducted using US population-based data (2010-2015) analyzed between January 1 and July 15, 2019. Data were obtained on 48 442 patients with nonvalvular atrial fibrillation who had received an index prescription of dabigatran, rivaroxaban, or apixaban between October 19, 2010, through June 30, 2015, with final follow-up on October 1, 2015. Analysis was restricted to individuals with no history of kidney disease who were receiving standard doses of the DOACs.ExposuresPatients with initial prescriptions of DOACs who were receiving verapamil or diltiazem were compared with those receiving amlodipine or metoprolol.Main outcomes and measuresOverall and gastrointestinal major, moderate, and minor bleeding using primary or secondary diagnoses. Hazard ratios and 95% CIs were estimated using inverse probability of treatment weights in Cox proportional hazards regression models.ResultsOf the 48 442 patients reviewed, analysis was conducted on 1764 patients receiving DOACs with verapamil or diltiazem compared with 3105 receiving amlodipine and 1793 patients receiving DOACs with verapamil or diltiazem compared with 3224 receiving metoprolol. Depending on the comparison, approximately 60% of the cohort were younger than 65 years and male, which differed by treatment group. Rivaroxaban and apixaban were not associated with increased rates of bleeding for patients receiving verapamil or diltiazem compared with those receiving amlodipine or metoprolol. Among patients receiving dabigatran etexilate, the overall bleeding rate was 52% higher (hazard ratio, 1.52; 95% CI, 1.05-2.20) with verapamil or diltiazem vs amlodipine and 43% higher (hazard ratio, 1.43; 95% CI, 1.02-2.00) vs metoprolol. Bleeding rates for dabigatran with verapamil or diltiazem were higher overall for other bleeding types (244.9 vs 158.4 per 1000 person-years; adjusted hazard ratios of overall GI bleeding: 2.16; 95% CI, 1.30-3.60; minor bleeding: 1.56; 95% CI, 1.07-2.27; and minor GI bleeding: 2.16; 95% CI, 1.29-3.63). Sensitivity analyses showed consistent results for dabigatran when used with verapamil and diltiazem, with magnitudes ranging from 50% to 100% increased hazard rates and no significant results for apixaban or rivaroxaban.Conclusions and relevanceCurrent US prescribing information only recommends prescribing changes with dabigatran and P-gp inhibitors with lower kidney function. This study found increased bleeding risk associated with dabigatran when used concomitantly with the P-gp inhibitors verapamil and diltiazem in individuals with normal kidney function. Clinicians and patients may need to consider these drug-drug interactions when choosing oral anticoagulation.

Project description:CONTEXT:Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE:To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES:Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ?65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS:Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS:In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

Project description:AimsThe increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function.Methods and resultsOverall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS2, Modified CHADS2, CHA2DS2-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2], mild CKD (eGFR 30-60 mL/min/1.73 m2), and advanced CKD (eGFR <30 mL/min/1.73 m2). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS2 score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration.ConclusionIn the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients.

Dataset Information

Association of Kidney Function With Risk of Adverse Effects of Therapies for Atrial Fibrillation.

Introduction

Methods

Results

Conclusion

Publications

Association of Kidney Function With Risk of Adverse Effects of Therapies for Atrial Fibrillation.

Similar Datasets

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