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Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Patients ?75 With Atrial Fibrillation.

ABSTRACT: Background Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. Methods and Results We studied 338 810 AF patients ?75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ?5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [HR], 1.16; 95% CI, 1.12-1.20) and heart failure (HR, 1.33; 95% CI, 1.29-1.36) but not ischemic stroke (HR, 0.96; 95% CI, 0.92-1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy (HR, 0.87; 95% CI, 0.76-0.99) than among those with polypharmacy (HR, 0.98; 95% CI, 0.91-1.07; P=0.02 for interaction). Conclusion Polypharmacy is common among patients ?75 with AF, is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ?75 may lead to improved outcomes.

SUBMITTER: Chen N

PROVIDER: S-EPMC7429010 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Patients ≥75 With Atrial Fibrillation.

Chen Nemin N Alam Aniqa B AB Lutsey Pamela L PL MacLehose Richard F RF Claxton J'Neka S JS Chen Lin Y LY Chamberlain Alanna M AM Alonso Alvaro A

Journal of the American Heart Association 20200523 11

Background Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. Methods and Results We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of <i>Internation ...[more]

PMID: 32448024

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Project description:BackgroundWomen with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed.MethodsWe studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex.ResultsAt the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34-1.49; HR men = 1.21, 95% CI 1.15-1.28, p < 0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke.ConclusionSex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

Project description:Background and purposeComparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown.MethodsWe used Medicare administrative data to evaluate patients with new atrial fibrillation diagnosis from 2015 to 2017, who initiated an oral anticoagulant within 90 days of diagnosis. Patients taking ≤3, 4 to 8, or ≥9 other prescription medications were categorized as having low, moderate, or high polypharmacy, respectively. Within polypharmacy categories, patients receiving apixaban 5 mg twice daily, rivaroxaban 20 mg once daily, or warfarin were matched using a 3-way propensity score matching. Study outcomes included ischemic stroke, bleeding, and all-cause mortality.ResultsThe study cohort included 6985 patients using apixaban, 3838 using rivaroxaban, and 6639 using warfarin. In the propensity-matched cohorts there was no difference in risk of ischemic stroke between the 3 drugs in patients with low and moderate polypharmacy. However, among patients with high polypharmacy, the risk of ischemic stroke was higher with apixaban compared with warfarin (adjusted hazard ratio 2.34 [95% CI, 1.01-5.42]; P=0.05) and similar to rivaroxaban (adjusted hazard ratio, 1.38 [95% CI, 0.67-2.84]; P=0.4). There was no difference in risk of death between the 3 drugs in patients with low and moderate polypharmacy, but apixaban was associated with a higher risk of death compared with rivaroxaban (adjusted hazard ratio, 2.03 [95% CI, 1.01-4.08]; P=0.05) in the high polypharmacy group. Apixaban had lower bleeding risk compared with warfarin in the low polypharmacy group (adjusted hazard ratio, 0.54 [95% CI, 0.32-0.90]; P=0.02), but there was no difference in bleeding between the 3 drugs in the moderate and high polypharmacy groups.ConclusionsOur study suggests that among patients with significant polypharmacy (>8 drugs), there may be a higher stroke and mortality risk with apixaban compared with warfarin and rivaroxaban. However, differences were of borderline significance.

Project description:Background and objectsFew studies focus on multimorbidity and polypharmacy in Chinese atrial fibrillation (AF) patients. We examined the impact of multimorbidity, polypharmacy, and treatment strategies on outcomes in Chinese emergency department (ED)AF patients. We also assessed factors associated with vitamin K antagonist (VKA) non-use in AF patients with multimorbidity or polypharmacy.Methods2015 AF patients who presented to emergency department (ED) were enrolled from Nov 2008 to Oct 2011, mean follow-up of 12-months. Cox regressions were performed to identify the impact of multimorbidity and polypharmacy on clinical outcomes.ResultsSix hundred and sixty-five patients in low morbidity group (≤1 comorbidity), 608 patients in moderate morbidity group (2 comorbidities), 742 patients in high morbidity group (≥3 comorbidities). Five hundred and seventy patients (28.3%) had polypharmacy (≥5 medications). High and moderate morbidity groups were significantly associated with a higher risk of all-cause death (HR 2.083, 95%CI 1.482-2.929; HR 1.713, 95%CI 1.198-2.449), CV death (HR 2.457, 95%CI 1.526-3.954; HR 1.974, 95%CI 1.206-3.232) and major bleeding (HR 4.126, 95%CI 1.022-16.664; HR 6.142, 95%CI 1.6789-22.369) compared with low morbidity group. In VKA subgroup, only high morbidity group was associated with a higher risk of all-cause death (HR 2.521, 95%CI 1.482-2.929), but not significantly in other events. For polypharmacy category, there were no significant statistics among these endpoints. Coronary artery disease (CAD), hypertension, chronic obstructive pulmonary disease, and antiplatelet therapy were independent predictors for VKA non-use in whole cohort, and patients with multimorbidity. CAD and antiplatelet therapy were independent predictors for VKA non-use in patients with polypharmacy.ConclusionMultimorbidity was associated with worse outcomes in Chinese ED AF patients. Polypharmacy showed no significant statistics among these outcomes. CAD and antiplatelet therapy were independent risk factors of VKA non-use in Chinese ED AF patients with multimorbidity or polypharmacy.

Project description:Background Patients with atrial fibrillation commonly have complex clinical backgrounds of multimorbidity and polypharmacy. The Atrial Fibrillation Better Care (ABC) pathway has been developed to help deliver integrated and holistic care for patients with atrial fibrillation. In this ancillary analysis, we assessed the adherence to and the effectiveness of the ABC pathway at reducing adverse outcomes in Chinese patients with atrial fibrillation with a complex clinical background of multimorbidity or polypharmacy. Methods and Results The ChiOTEAF (Optimal Thromboprophylaxis in Elderly Chinese Patients With Atrial Fibrillation) registry is a prospective, multicenter, nationwide study conducted from October 2014 to December 2018. The primary outcomes of interest were the composite end point of all-cause death and thromboembolic events, as well as individual end points of all-cause death, thromboembolic events, and major bleeding. Multimorbidity was defined as the presence of ≥2 comorbidities, and polypharmacy was defined as the concomitant use of ≥5 medications. The eligible cohort included 4644 patients with multimorbidity, of whom 2610 (56.2%) had available data to assess the ABC pathway usage (mean age, 74.4±10.2; 42.8% women). Among patients with polypharmacy (n=2262; mean age, 74.6±10.1; 43.3% women), 1328 (58.7%) had available data to assess the use of the ABC pathway. Adherence to the ABC pathway was associated with a lower risk of the primary composite outcome among patients with multimorbidity (odds ratio, 0.48; 95% CI, 0.29-0.79) and in the polypharmacy group (odds ratio, 0.39; 95% CI, 0.19-0.78). Health-related quality of life was lower in the non-ABC-adherent group compared with the ABC-treated patients. Conclusions This nationwide real-world registry shows that adherence to the ABC pathway is associated with improved clinical outcomes and health-related quality of life in clinically complex Chinese patients with atrial fibrillation with multimorbidity or polypharmacy.

Project description:ImportanceThe CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata.ObjectiveTo evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group.Design, setting, and participantsThis cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019.ExposureInitiation of oral anticoagulants.Main outcomes and measuresWe observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes.ResultsWe identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends.Conclusions and relevanceThe observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Dataset Information

Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Patients ?75 With Atrial Fibrillation.

Publications

Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Patients ≥75 With Atrial Fibrillation.

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