The effect of age on the association between diabetes and mortality in adult patients with COVID-19 in Mexico

AbstractDiabetes is associated with severe COVID-19 and mortality. The aim of the present study was to determine the effect of age on the association between diabetes and mortality in patients with laboratory-confirmed COVID-19 in Mexico. This retrospective cohort study involved patients aged 20 years or older with symptoms of viral respiratory disease who were screened for SARS-CoV-2 infection across the System of Epidemiological Surveillance of Viral Respiratory Disease in Mexico from January 1 through November 4, 2020. Cox proportional-hazard regression was used to calculate the hazard ratio for 28-day mortality and its 95% confidence interval (CI). Among 757,210 patients with COVID-19 (outpatients and inpatients), 120,476 (16%) had diabetes and 80,616 died. Among 878,840 patients without COVID-19 (those who tested negative for SARS-CoV-2 infection), 88,235 (10.0%) had diabetes and 20,134 died. Among patients with COVID-19, diabetes was associated with a hazard ratio for death of 1.49 (95% CI 1.47–1.52), adjusting for age, sex, smoking habit, obesity, hypertension, immunodeficiency, and cardiovascular, pulmonary, and chronic renal disease. The strength of the association decreased with age (trend test: P = 0.004). For example, the adjusted hazard ratio for death was 3.12 (95% CI 2.86–3.40) for patients 20–39 years of age; in contrast, the adjusted hazard ratio of death for patients 80 years of age or older was 1.11 (95% CI 1.06–1.16). The adjusted hazard ratios were 1.66 (95% CI 1.58–1.74) in outpatients and 1.14 (95% CI 1.12–1.16) in inpatients. In hospitalized patients 80 years of age or older, no association was observed between diabetes and COVID-19-related mortality (adjusted hazard ratio: 1.03; 95% CI 0.98–1.08). Among patients without COVID-19, the adjusted hazard ratio for death was 1.78 (95% CI 1.73–1.84). In conclusion, in adult patients with COVID-19 in Mexico, the risk of death associated with diabetes decreased with age. No association between diabetes and mortality was observed among inpatients 80 years of age or older. Our findings should be verified in other populations.

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Diabetes and Mortality Among 1.6 Million Adult Patients Screened for SARS-CoV-2 in Mexico

10.1101/2020.11.25.20238345 ◽

2020 ◽

Author(s):

Orison O. Woolcott ◽

Juan P. Castilla-Bancayán

Keyword(s):

Relative Risk ◽

Chronic Renal Disease ◽

Smoking Habit ◽

Case Series ◽

Hazard Ratio ◽

Adult Patients ◽

Epidemiological Surveillance ◽

Risk Of Death ◽

Case Series Study ◽

Relative Risk Of Death

ABSTRACTBackgroundWhether diabetes is associated with COVID-19-related mortality remains unclear.MethodsIn this retrospective case-series study we examined the risk of death associated with self-reported diabetes in symptomatic adult patients with laboratory-confirmed COVID-19 who were identified through the System of Epidemiological Surveillance of Viral Respiratory Disease in Mexico from January 1 through November 4, 2020. Survival time was right-censored at 28 days of follow-up.ResultsAmong 757,210 patients with COVID-19 included in the study, 120,476 (16%) had diabetes and 80,616 died. Patients with diabetes had a 49% higher relative risk of death than those without diabetes (Cox proportional-hazard ratio; 1.49 (95% confidence interval [CI], 1.47-1.52), adjusting for age, sex, smoking habit, obesity, hypertension, immunodeficiency, and cardiovascular, pulmonary, and chronic renal disease. The relative risk of death associated with diabetes decreased with age (P=0.004). The hazard ratios were 1.66 (1.58-1.74) in outpatients and 1.14 (1.12-1.16) in hospitalized patients. The 28-day survival for inpatients with and without diabetes was, respectively, 73.5% and 85.2% for patients 20-39 years of age; 66.6% and 75.9% for patients 40-49 years of age; 59.4% and 66.5% for patients 50-59 years of age; 50.1% and 54.6% for patients 60-69 years of age; 42.7% and 44.6% for patients 70-79 years of age; and 38.4% and 39.0% for patients 80 years of age or older. In patients without COVID-19 (878,840), the adjusted hazard ratio for mortality was 1.78 (1.73-1.84).ConclusionIn symptomatic adult patients with COVID-19 in Mexico, diabetes was associated with higher mortality. This association decreased with age.

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FRAILTY AND MORTALITY RISK IN PATIENTS WITH SEVERE COVID-19: PROGNOSIS BEYOND THE AGE CRITERION

10.5327/z2447-21232021res05 ◽

2021 ◽

Author(s):

Márlon Juliano Romero Aliberti ◽

Claudia Szlejf ◽

Claudia Kimie Suemoto ◽

Murilo Bacchini Dias ◽

Wilson Jacob-Filho ◽

...

Keyword(s):

Disease Severity ◽

Scale Score ◽

Mortality Risk ◽

Frailty Index ◽

Hazard Ratio ◽

Hospitalized Patients ◽

Adjusted Hazard Ratio ◽

Acute Disease ◽

Clinical Frailty Scale ◽

Risk Of Death

OBJECTIVE: To investigate the association between frailty and death in hospitalized patients with COVID-19. METHODOLOGY: Prospective cohort study with patients ≥ 50 years hospitalized with COVID-19. Frailty was assessed using the Clinical Frailty Scale and the frailty index. Patients with a Clinical Frailty Scale score ≥ 5 were considered frail. The primary endpoints were mortality at 30 and 100 days after hospital admission. We used Cox proportional hazard models to investigate the association between frailty and mortality. We also explored whether frailty predicted different mortality levels among patients within strata of similar age and acute disease severity (Sequential Organ Failure Assessment score). RESULTS: A total of 1,830 patients were included (mean age 66 years; 58% men; 27% frail according to Clinical Frailty Scale score). The mortality risk at 30 days (adjusted hazard ratio = 1.7; 95% CI 1.4 - 2.1; p <0.001) and 100 days (adjusted hazard ratio = 1.7; 95% CI 1.4 - 2.1; p <0.001) was almost double for frail patients. The Clinical Frailty Scale also predicted different mortality levels among patients within strata of similar age and acute disease severity. Frailty intensified the effect of acute disease severity on the risk of death (p for interaction = 0.01). Of note, the Clinical Frailty Scale achieved outstanding accuracy to identify frailty according to the frailty index (area under the ROC curve = 0.94; 95% CI 0.93 - 0.95). CONCLUSIONS: Our results encourage the use of the Clinical Frailty Scale in association with measures of acute disease severity to determine prognosis and promote adequate resource allocation in hospitalized patients with COVID-19.

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Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19

10.1101/2020.04.16.20065920 ◽

2020 ◽

Cited By ~ 73

Author(s):

Joseph Magagnoli ◽

Siddharth Narendran ◽

Felipe Pereira ◽

Tammy Cummings ◽

James W. Hardin ◽

...

Keyword(s):

United States ◽

Mechanical Ventilation ◽

Propensity Scores ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Veterans Health ◽

Health Administration ◽

Subdistribution Hazard ◽

Risk Of Death ◽

Randomized Controlled Studies

ABSTRACTBACKGROUNDDespite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19, the U.S. Food and Drug Administration has authorized the emergency use of this drug when clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited observational evidence.METHODSWe performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19. The two primary outcomes were death and the need for mechanical ventilation. We determined the association between treatment and the primary outcomes using competing risk hazard regression adjusting for clinical characteristics via propensity scores. Discharge and death were taken into account as competing risks and subdistribution hazard ratios are presented.RESULTSA total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72). The risk of ventilation was similar in the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group.CONCLUSIONSIn this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.

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Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.757484 ◽

2021 ◽

Vol 11 ◽

Author(s):

Haorui Zhang ◽

Bocen Chen ◽

Zixiu Zou ◽

Jian Feng ◽

Yutao Li ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Single Nucleotide ◽

Risk Of Death ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

BackgroundThe 5-year survival rate of patients with lung cancer in China is less than 20% and predicting their prognosis is challenging. We investigated the association between a common non-synonymous single nucleotide polymorphism (SNP), rs7214723, in the Ca2+/calmodulin-dependent protein kinase kinase 1 (CAMKK1) gene and the prognosis of patients with lung cancer.MethodsGenomic DNA was extracted from the blood samples of 839 patients with lung cancer, recruited from Changhai Hospital (n = 536) and Taizhou Institute of Health Sciences (n = 352), and genotyped using the SNPscan technique. The association between patient prognosis and the genotypic data for CAMKK1 was analyzed using a multivariate Cox proportional hazards model adjusted for multiple potential confounders. The CRISPR/Cas9 gene-editing system was used to introduce point mutations in the CAMKK1 rs7214723 of A549 and NCI-H358 cells. Subsequently, Cell proliferation and migration ability were assessed with the Cell Counting Kit-8 and scratch assay. The Annexin V-FITC apoptosis detection kit was used to detect cell apoptosis.ResultsThe CAMKK1 rs7214723 recessive CC genotype conferred significantly better overall survival (CC vs. TT + TC: adjusted hazard ratio = 0.78, 95% confidence interval [CI], 0.61-1.00, P = 0.049) than the TT + TC genotypes. Stratified analysis showed that the CAMKK1 rs7214723 CC genotype and recessive CC genotype conferred a significantly decreased risk of death in patients who were male, had a smoking history, or had stage III + IV cancer, compared with the TT and TT + TC genotypes. Relative to the TT + TC genotypes, the rs7214723 recessive CC genotype was also associated with a decreased risk of death in patients aged < 60 years (CC vs. TT + TC: adjusted hazard ratio = 0.59, 95% CI, 0.37-0.93, P = 0.024) and patients with squamous cell carcinoma (CC vs. TT + TC: adjusted hazard ratio = 0.65, 95% CI, 0.44-0.98, P = 0.038). Remarkably, CRISPR/Cas9-guided single nucleotide editing demonstrated that CAMKK1 rs7214723 T > C mutation significantly inhibits cell proliferation and migration and promotes cell apoptosis.ConclusionsCAMKK1 SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer.

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Benzodiazepines, Codispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.13341019 ◽

2020 ◽

Vol 15 (6) ◽

pp. 794-804 ◽

Cited By ~ 1

Author(s):

Abimereki D. Muzaale ◽

Matthew Daubresse ◽

Sunjae Bae ◽

Nadia M. Chu ◽

Krista L. Lentine ◽

...

Keyword(s):

Confidence Interval ◽

Mortality Risk ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Opioid Prescription ◽

Short Acting ◽

Risk Of Death ◽

Medicare Claims ◽

Long Acting

Background and objectivesMortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis.Design, setting, participants, & measurementsThe cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing.ResultsWithin 1 year of hemodialysis initiation, 10,854 (16%) patients were dispensed a short-acting benzodiazepine, and 3262 (5%) patients were dispensed a long-acting benzodiazepine. Among those who were dispensed a benzodiazepine during follow-up, codispensing of opioids and short-acting benzodiazepines occurred among 3819 (26%) patients, and codispensing of opioids and long-acting benzodiazepines occurred among 1238 (8%) patients. Patients with an opioid prescription were more likely to be subsequently dispensed a short-acting benzodiazepine (adjusted hazard ratio, 1.66; 95% confidence interval, 1.59 to 1.74) or a long-acting benzodiazepine (adjusted hazard ratio, 1.11; 95% confidence interval, 1.03 to 1.20). Patients dispensed a short-acting benzodiazepine were at a 1.45-fold (95% confidence interval, 1.35 to 1.56) higher mortality risk compared with those without a short-acting benzodiazepine; among those with opioid codispensing, this risk was 1.90-fold (95% confidence interval, 1.65 to 2.18; Pinteraction<0.001). In contrast, long-acting benzodiazepine dispensing was inversely associated with mortality (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72 to 0.99) compared with no dispensing of long-acting benzodiazepine; there was no differential risk by opioid dispensing (Pinteraction=0.72).ConclusionsCodispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.

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BMI and all-cause mortality among middle-aged and older adults in Taiwan: a population-based cohort study

Public Health Nutrition ◽

10.1017/s136898001400281x ◽

2014 ◽

Vol 18 (10) ◽

pp. 1839-1846 ◽

Cited By ~ 13

Author(s):

Wei-Sheng Chung ◽

Feng-Ming Ho ◽

Nan-Cheng Cheng ◽

Meng-Chih Lee ◽

Chih-Jung Yeh

Keyword(s):

Older Adults ◽

Cohort Study ◽

Population Based ◽

Normal Weight ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Middle Aged ◽

Obese People ◽

Risk Of Death ◽

All Cause Mortality

AbstractObjectiveThe present study investigates the relationship between BMI and all-cause mortality among middle-aged and older adults with or without pre-existing diseases.DesignA population-based cohort study.SettingThe Taiwan Longitudinal Study on Aging is a nationwide prospective cohort study comprising a representative random sample of middle-aged and older adults. The study period was 1996–2007.SubjectsWe followed 4145 middle-aged and older adults, totalling 42 353 person-years.ResultsOverweight and mildly obese participants showed a 16 % and 30 % decrease in the risk of death, respectively, compared with those of normal weight after adjusting for potential covariates (e.g. demographic characteristics, health behaviour, co-morbidities and physical function). Underweight adults showed a 1·36-fold increased adjusted hazard ratio of death compared with normal-weight adults. Adults with a BMI of 27·0–28·0 kg/m2 showed a significantly lower adjusted hazard ratio of all-cause mortality rate compared with adults who had normal BMI values when they had coexisting hypertension or diabetes (adjusted hazard ratio=0·50; 95 % CI 0·30, 0·81 for hypertension and adjusted hazard ratio=0·41; 95 % CI 0·18, 0·89 for diabetes).ConclusionsThe study demonstrates that underweight people have a higher risk of death, and overweight and mildly obese people have a lower risk of death, compared with people of normal weight among middle-aged and older adults. An optimal BMI may be based on the individual, who exhibits pre-existing diseases or not.

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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes

10.2337/figshare.16775743 ◽

2021 ◽

Author(s):

Anca Balintescu ◽

Marcus Lind ◽

Mikael Andersson Franko ◽

Anders Oldner ◽

Maria Cronhjort ◽

...

Keyword(s):

Type 2 Diabetes ◽

Regression Analysis ◽

Cox Regression ◽

Cubic Spline ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk

Objective To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes and to assess the association of sepsis and all-cause mortality in such patients. Research design and methods We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between January 1, 2005 and December 31, 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. Result Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%); 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%); 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%); 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%); and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per standard deviation, and increased thereafter (P for non-linearity <0.001). As compared to patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30). Conclusions In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a four-fold increased risk of death among those developing sepsis.

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Risk of ischemic stroke in patients with acute myocardial infarction and new atrial fibrillation: a nationwide analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.0514 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

L Fauchier ◽

A Bisson ◽

A Bodin ◽

J Herbert ◽

T Genet ◽

...

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Acute Myocardial Infarction ◽

Ischemic Stroke ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Risk Of Death ◽

Increased Risk ◽

History Of

Abstract Background In patients with acute myocardial infarction (AMI), history of atrial fibrillation (AF) and new onset AF during the early phase may be associated with a worse prognosis. Whether both conditions are associated with a similar risk of stroke and should be similarly managed is a matter of debate. Methods Based on the administrative hospital-discharge database, we collected information for all patients treated with AMI between 2010 and 2019 in France. The adverse outcomes were investigated during follow-up. Results Among 797,212 patients with STEMI or NSTEMI, 146,922 (18.4%) had history of AF, and 11,824 (1.5%) had new AF diagnosed between day 1 and day 30 after AMI. Patients with new AF were older and had more comorbidities than those with no AF but were younger and had less comorbidities than those with history of AF. Both groups with history of AF or new AF had less frequent STEMI and anterior MI, less frequent use of percutaneous coronary intervention but more frequent HF at the acute phase than patients with no AF. During follow-up (mean [SD] 1.8 [2.4] years, median [interquartile range] 0.7 [0.1–3.1] years), 163,845 deaths and 20,168 ischemic strokes were recorded. Using Cox multivariable analysis, compared to patients with no AF, history of AF was associated with a higher risk of death during follow-up (adjusted hazard ratio HR 1.06 95% CI 1.05–1.08) while this was not the case for patients with new AF (adjusted HR 0.98 95% CI 0.95–1.02). By contrast, both history of AF and new AF were associated with a higher risk of ischemic stroke during follow-up compared to patients with no AF: adjusted hazard ratio HR 1.29 95% CI 1.25–1.34 for history of AF, adjusted HR 1.72 95% CI 1.59–1.85 for new AF. New AF was associated with a higher risk of ischemic stroke than history of AF (adjusted HR 1.38 95% CI 1.27–1.49). Conclusion In a large and systematic nationwide analysis, AF first recorded in the first 30 days after AMI was associated with an increased risk of ischemic stroke. Specific management should be considered in order to improve outcomes in these patients after AMI. Funding Acknowledgement Type of funding source: None

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Molecular Prognosis in Multiple Myeloma: The IFM Experience.

Blood ◽

10.1182/blood.v108.11.3491.3491 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3491-3491

Author(s):

Olivier Decaux ◽

Florence Magrangeas ◽

Laurence Lode ◽

Catherine Charbonnel ◽

Wilfried Gouraud ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

High Risk ◽

Training Group ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

High Dose ◽

Validation Group ◽

Risk Of Death ◽

Biological Variables

Abstract Multiple myeloma is the second most common hematological malignancy and remains incurable despite high dose chemotherapy. Patients experience survival periods of few months to more than ten years. We used gene-expression profiles of malignant plasma cells obtained at diagnosis to develop and validate biomarkers to predict disease prognosis. Gene-expression profiling was realized on 250 bone marrow samples obtained from patients less than 66 years, treated according to the Intergroupe Francophone du Myelome (IFM) 99 clinical trials, based on double intensive treatments. The median follow-up time was 3 years and 55 patients died from their disease during this period. Supervised methods were performed to identify expression signatures associated with survival in a training group of 182 patients. From these genes, a classifier of prognosis was developed in the training group and validated in an independent validation group of 68 patients. Univariate Cox proportional hazards model at a significant level of p<0.05 and selection procedure from BRB ArrayTools at a significant level of p<0.001 were used to select 50 genes associated with survival. Resampling and permutation tests were performed in an rigorous internal validation procedure and 28 genes with a permutation p<0.005 and a resampling mean p<0.01 were retained. To reduce gene list instability, multiple training/test partitions (100) were performed and the 15 most stable genes were used to build a survival predictor. For each patient, a score based on the first component of principal component analysis was calculated. The patients were ranked according to their score and divided according to the median (low-risk and high-risk). The model was highly significantly associated with survival in the training group (p<0.001) and it was confirmed in the validation group (p<0.001). The relative risk of death for high-risk patients was 8.46 (95% confidence interval (CI) = 3.3 to 21.6) in the training group and was 15.3 (95% CI = 2 to 116.5) in the validation group. Various biological variables including serum beta2-microglobulin, serum albumin, combined in the International Staging System (ISS), the deletions/monosomy of chromosome 13 (del13) and the t(4;14)(p16;q32) have emerged as relevant prognostic factors in MM. The 15-gene prognostic classifier was independent of ISS (p<0.001) with an adjusted hazard ratio of death =7.5 (95% CI = 3.09 to 18.2), of del13 (p<0.001) with an adjusted hazard ratio of death =8.8 (95% CI = 3.7 to 21), and of t(4;14) (p<0.001) with an adjusted hazard ratio of death =9.3 (95% CI = 3.9 to 22.1). These results demonstrate that this molecular predictor is very powerful to identify different categories of patients based on expected survival, and thus may be clinically useful to design therapeutic trials. Figure Figure

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Comparative Effectiveness of Rivaroxaban, Apixaban, and Warfarin in Atrial Fibrillation Patients With Polypharmacy

Stroke ◽

10.1161/strokeaha.120.029541 ◽

2020 ◽

Vol 51 (7) ◽

pp. 2076-2086 ◽

Cited By ~ 1

Author(s):

Amgad Mentias ◽

Eric Heller ◽

Mary Vaughan Sarrazin

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Comparative Effectiveness ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Study Cohort ◽

Prescription Medications ◽

Risk Of Death

Background and Purpose: Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown. Methods: We 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. Results: The 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. Conclusions: Our 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.

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