Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study

ObjectivesSARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.DesignThis is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality.SettingMedical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality.Participants9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.Outcome measureDeath from any cause within 60 days of COVID-19 diagnosis was examined.ResultsDiscontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2–1.7). Initiating (OR: 0.3; 95% CI 0.2–0.5) or continuous (OR: 0.6; 95% CI 0.5–0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment.ConclusionsRecent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.

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Ethnicity, pre-existing comorbidities, and outcomes of hospitalised patients with COVID-19

Wellcome Open Research ◽

10.12688/wellcomeopenres.16580.2 ◽

2021 ◽

Vol 6 ◽

pp. 32

Author(s):

Gillian Santorelli ◽

Michael McCooe ◽

Trevor A. Sheldon ◽

John Wright ◽

Tom Lawton

Keyword(s):

South Asian ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Older Age ◽

Risk Of Death ◽

Asian Patients ◽

Hospitalised Patients ◽

Increased Risk ◽

Minority Ethnic ◽

White Patients

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in thousands of deaths in the UK. Those with existing comorbidities and minority ethnic groups have been found to be at increased risk of mortality. We wished to determine if there were any differences in intensive care unit (ICU) admission and 30-day hospital mortality in a city with high levels of deprivation and a large community of people of South Asian heritage. Methods: Detailed information on 582 COVID-19-positive inpatients in Bradford and Calderdale between February-August 2020 were extracted from Electronic Health Records. Logistic regression and Cox proportional hazards models were used to explore the relationship between ethnicity with admission to ICU and 30-day mortality, respectively accounting for the effect of demographic and clinical confounders. Results: The sample consisted of 408 (70%) White, 142 (24%) South Asian and 32 (6%) other minority ethnic patients. Ethnic minority patients were younger, more likely to live in deprived areas, and be overweight/obese, have type 2 diabetes, hypertension and asthma compared to white patients, but were less likely to have cancer (South Asian patients only) and COPD. Male and obese patients were more likely to be admitted to ICU, and patients of South Asian ethnicity, older age, and those with cancer were less likely. Being male, older age, deprivation, obesity, and cancer were associated with 30-day mortality. The risk of death in South Asian patients was the same as in white patients HR 1.03 (0.58, 1.82). Conclusions: Despite South Asian patients being less likely to be admitted to ICU and having a higher prevalence of diabetes and obesity, there was no difference in the risk of death compared to white patients. This contrasts with other findings and highlights the value of studies of communities which may have different ethnic, deprivation and clinical risk profiles.

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Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people

Heart ◽

10.1136/heartjnl-2020-317393 ◽

2020 ◽

Vol 106 (19) ◽

pp. 1503-1511 ◽

Cited By ~ 34

Author(s):

Julia Hippisley-Cox ◽

Duncan Young ◽

Carol Coupland ◽

Keith M Channon ◽

Pui San Tan ◽

...

Keyword(s):

Cohort Study ◽

Ace Inhibitors ◽

Ace Inhibitor ◽

Proportional Hazards ◽

Angiotensin Receptor Blockers ◽

Cox Proportional Hazards ◽

Angiotensin Receptor ◽

Black African ◽

Increased Risk ◽

Wide Range

BackgroundThere is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.MethodsThis was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20–99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.FindingsOf 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.InterpretationACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.

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Ethnicity, pre-existing comorbidities, and outcomes of hospitalised patients with COVID-19

Wellcome Open Research ◽

10.12688/wellcomeopenres.16580.1 ◽

2021 ◽

Vol 6 ◽

pp. 32

Author(s):

Gillian Santorelli ◽

Michael McCooe ◽

Trevor A. Sheldon ◽

John Wright ◽

Tom Lawton

Keyword(s):

South Asian ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Older Age ◽

Risk Of Death ◽

Asian Patients ◽

Hospitalised Patients ◽

Increased Risk ◽

Minority Ethnic ◽

White Patients

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in thousands of deaths in the UK. Those with existing comorbidities and minority ethnic groups have been found to be at increased risk of mortality. We wished to determine if there were any differences in intensive care unit (ICU) admission and 30-day hospital mortality in a city with high levels of deprivation and a large community of people of South Asian heritage. Methods: Detailed information on 622 COVID-19-positive inpatients in Bradford and Calderdale between February-August 2020 were extracted from Electronic Health Records. Logistic regression and Cox proportional hazards models were used to explore the relationship between ethnicity with admission to ICU and 30-day mortality, respectively accounting for the effect of demographic and clinical confounders. Results: The sample consisted of 408 (70%) White, 142 (24%) South Asian and 32 (6%) other minority ethnic patients. Ethnic minority patients were younger, more likely to live in deprived areas, and be overweight/obese, have type 2 diabetes, hypertension and asthma compared to white patients, but were less likely to have cancer (South Asian patients only) and COPD. Male and obese patients were more likely to be admitted to ICU, and patients of South Asian ethnicity, older age, and those with cancer were less likely. Being male, older age, deprivation, obesity, and cancer were associated with 30-day mortality. The risk of death in South Asian patients was the same as in white patients HR 1.03 (0.58, 1.82). Conclusions: Despite South Asian patients being less likely to be admitted to ICU and having a higher prevalence of diabetes and obesity, there was no difference in the risk of death compared to white patients. This contrasts with other findings and highlights the value of studies of communities which may have different ethnic, deprivation and clinical risk profiles.

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Accelerated aging and mortality in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10045 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10045-10045

Author(s):

AnnaLynn M. Williams ◽

Jeanne S. Mandelblatt ◽

Mingjuan Wang ◽

Kirsten K. Ness ◽

Gregory T. Armstrong ◽

...

Keyword(s):

Childhood Cancer ◽

Proportional Hazards ◽

Accelerated Aging ◽

Cox Proportional Hazards ◽

Premature Aging ◽

Self Report ◽

Deficit Accumulation ◽

Risk Of Death ◽

Increased Risk ◽

Survivors Of Childhood Cancer

10045 Background: Survivors of childhood cancer have functional limitations and health-related morbidity consistent with an accelerated aging phenotype. We characterized aging using a Deficit Accumulation Index (DAI) which examines the accumulation of multiple aging-related deficits readily available from medical records and self-report. DAI’s are used as surrogates of biologic aging and are validated to predict mortality in adult cancer patients. Methods: We included childhood cancer survivors (N = 3,758, mean age 30 [SD 8], 22 [9] years post diagnosis, 52% male) and community controls (N = 575, mean age 34 [10] 44% male) who completed clinical assessments and questionnaires and who were followed for mortality through December 31st, 2018 (mean follow-up 6.1 [3.1] years). Using the initial SJLIFE clinical assessment, a DAI score was generated as the proportion of deficits out of 44 items related to aging, including chronic conditions (e.g. hearing loss, hypertension), psychosocial and physical function, and activities of daily living. The total score ranged 0 to 1; scores > 0.20 are robust, while moderate and large clinically meaningful differences are 0.02 and 0.06, respectively. Linear regression compared the DAI in survivors and controls with an age*survivor/control interaction and examined treatment associations in survivors. Cox-proportional hazards models estimated risk of death associated with DAI. All models were adjusted for age, sex, and race. Results: Mean [SD] of DAI was 0.17 [0.11] for survivors and 0.10 [0.08] for controls. 32% of survivors had a DAI above the 90th percentile of the control distribution (p < 0.001). After adjustment for covariates, survivors had a statistically and clinically meaningfully higher DAI score than controls (β = 0.072 95%CI 0.062, 0.081; p < 0.001). When plotted against age, the adjusted DAI at the average age of survivors (30 years) was 0.166 (95% CI 0.160,0.171), which corresponded to 60 years of age in controls, suggesting premature aging of 30 years. The mean difference in DAI between survivors and controls increased with age from 0.06 (95% CI 0.04, 0.07) at age 20 to 0.11 (95% CI 0.08, 0.13) at age 60, consistent with an accelerated aging phenotype (p = 0.014). Cranial radiation, abdominal radiation, cyclophosphamide, platinum agents, neurosurgery, and amputation were each associated with a higher DAI (all p≤0.001). Among survivors, a 0.06 increase in DAI was associated with a 41% increased risk of all-cause mortality (HR 1.41 95%CI 1.32, 1.50; p < 0.001). Conclusions: Survivors of childhood cancer experience significant age acceleration that is associated with an increased risk of mortality; longitudinal analyses are underway to validate these findings. Given the ease of estimating a DAI, this may be a feasible method to quickly identify survivors for novel and tailored interventions that can improve health and prevent premature mortality.

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Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Frontiers in Medicine ◽

10.3389/fmed.2021.639970 ◽

2021 ◽

Vol 8 ◽

Author(s):

Augusto Di Castelnuovo ◽

Simona Costanzo ◽

Andrea Antinori ◽

Nausicaa Berselli ◽

Lorenzo Blandi ◽

...

Keyword(s):

Observational Study ◽

Propensity Scores ◽

Proportional Hazards ◽

Real Life ◽

Cox Proportional Hazards ◽

Event Analysis ◽

Multicenter Observational Study ◽

Protein Levels ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

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Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Viruses ◽

10.3390/v10110658 ◽

2018 ◽

Vol 10 (11) ◽

pp. 658 ◽

Cited By ~ 2

Author(s):

Paul Blair ◽

Maryam Keshtkar-Jahromi ◽

Kevin Psoter ◽

Ronald Reisler ◽

Travis Warren ◽

...

Keyword(s):

Proportional Hazards ◽

Clinical Laboratory ◽

Cynomolgus Macaque ◽

The United States ◽

Cox Proportional Hazards ◽

Marburg Virus ◽

Time To Death ◽

Risk Of Death ◽

Published Evidence ◽

Increased Risk

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.

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The performance of the EMS triage (RETTS-p) and the agreement between the field assessment and final hospital diagnosis: a prospective observational study among children < 16 years

BMC Pediatrics ◽

10.1186/s12887-019-1857-0 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Carl Magnusson ◽

Johan Herlitz ◽

Thomas Karlsson ◽

Maria Jiménez-Herrera ◽

Christer Axelsson

Keyword(s):

Observational Study ◽

Prospective Observational Study ◽

Hospital Setting ◽

Risk Of Death ◽

Computerised Decision Support System ◽

Field Assessment ◽

Hospitalised Patients ◽

Increased Risk ◽

Life Threatening ◽

Triage Level

Abstract Background The rapid triage and treatment system for paediatrics (RETTS-p) has been used by the emergency medical services (EMS) in the west of Sweden since 2014. The performance of the RETTS-p in the pre-hospital setting and the agreement between the EMS nurse’s field assessment and the hospital diagnosis is unknown. The aim of this study was to evaluate the performance of the RETTS-p in the EMS and the agreement between the EMS field assessment and the hospital diagnosis. Methods A prospective observational study was conducted among 454 patients < 16 years of age who were assessed and transported to the PED. Two instruments were used for comparison: 1) Classification of an emergent patient according to predefined criteria as compared to the RETTS-p and 2) Agreement between the EMS nurse’s field assessment and the hospital diagnosis. Results Among all children, 11% were identified as having vital signs associated with an increased risk of death and 7% were diagnosed in hospital with a potentially life-threatening condition. Of the children triaged with RETTS-p (85.9%), 149 of 390 children (38.2%) were triaged to RETTS-p red or orange (life-threatening, potentially life-threatening), of which 40 (26.8%) children were classified as emergent. The hospitalised children were triaged with the highest frequency to level yellow (can wait; 41.5%). In children with RETTS-p red or orange, the sensitivity for a defined emergent patient was 66.7%, with a corresponding specificity of 67.0%. The EMS field assessment was in agreement with the final hospital diagnosis in 80% of the cases. Conclusions The RETTS-p sensitivity in this study is considered moderate. Two thirds of the children triaged to life threatening or potentially life threatening were later identified as non-emergent. Of those, one in six was discharged from the PED without any intervention. Further, one third of the children were under triaged, the majority were found in the yellow triage level (can wait). The highest proportion of hospitalised patients was found in the yellow triage level. Our result is in agreement with previous studies using other triage instruments. A computerised decision support system might help the EMS triage to increase sensitivity and specificity.

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Brain metastases in breast cancer: Different survival by biological subtype and Ki67 expression

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1069 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1069-1069

Author(s):

D. Sartori ◽

M. Bari ◽

G. L. Pappagallo ◽

F. Rosetti ◽

S. Olsen ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Proportional Hazards ◽

Fold Increase ◽

Cox Proportional Hazards ◽

Her2 Overexpression ◽

Cns Metastases ◽

Risk Of Death ◽

Pathologic Features ◽

Increased Risk

1069 Background: Ten to 15% of patients (pts) with breast cancer will be diagnosed with central nervous system (CNS) metastases, and autopsy series suggest that up to 30% of pts have evidence of CNS disease at the time of death. The idenfication of factors that may predispose to CNS metastasis may help lead to earlier detection and possibly to improvement in disease management. Methods: Breast cancer pts with CNS metastases were identified within a database of 1300 breast cancer diganoses from 1995 to 2007 at the Department of Oncology, Azienda ULSS 13 VE. Pathologic features of tumor samples were examined using standard immunohistochemical assays. Results: Fifty-one pts with CNS metastases were identified. Median age at primary breast cancer diagnosis was 49 years (range, 28–78); median time to CNS metastases was 45 months (range, 3–244). HER2 overexpression was found in tumors from 25 pts (49.0%); 23 pts had tumors lacking overexpression of HER2, estrogen receptors (ER), and progesterone receptors (PgR) (ie, “triple negative” disease). Overexpression of p53 (at least 20% tumor cells positive), Ki67 (at least 20%), and BCL2 (at least 30%) were detected in tumors from 16 pts (31.4%), 32 pts (62.7%), and 14 pts (27.5%), respectively. Median survival from CNS involvement was 3.67 months (95% CI 2.05–5.28), with 24.4% and 15.3% of patients estimated to be alive at 12 and 24 months, respectively (Kaplan-Meier product limit method). A Cox proportional hazards analysis found that Ki67 overexpression was the only factor independently associated with a significantly increased risk of death (2.7-fold increase, p=0.028), while triple negative status was associated with a 1.8-fold increase in the risk of death (P=0.08) (Table). Conclusions: In our series of breast cancer pts with CNS metastases, nearly all had either HER2 overexpression or triple-negative disease. Pts whose tumors had higher proliferative indices, assessed by Ki67, had the poorest prognosis. [Table: see text] [Table: see text]

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Characteristics and outcomes of an international cohort of 400,000 hospitalised patients with Covid-19

10.1101/2021.09.11.21263419 ◽

2021 ◽

Author(s):

◽

Christiana Kartsonaki

Keyword(s):

Clinical Outcomes ◽

Proportional Hazards ◽

Invasive Mechanical Ventilation ◽

Case Fatality ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Hospitalised Patients ◽

Male Sex ◽

Viable Model

Background: Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world's largest international, standardised cohort of hospitalised patients. Methods: The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV). Findings: 439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients. Interpretation: The size of our international database and the standardized data collection method makes this study a reliable and comprehensive international description of COVID-19 clinical features. This is a viable model to be applied to future epidemics.

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Early hemoglobin decline and survival prognosis in epoetin alfa studies

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9625 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9625-9625

Author(s):

J. A. Berlin ◽

P. J. Bowers ◽

S. Rao ◽

S. Sun ◽

K. Liu ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Time Dependent ◽

Epoetin Alfa ◽

Survival Prognosis ◽

Proportional Hazards Models ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Level Data ◽

Increased Risk

9625 Background: When cancer patients (pts) with chemotherapy-induced anemia (CIA) respond to erythropoietic-stimulating agents (ESA), hemoglobin (Hb) typically increases within 4–8 weeks. This exploratory analysis examined whether mortality differs depending on Hb response after 4 or 8 weeks of epoetin alfa (EPO) treatment or depending on transfusion. Methods: Pt-level data were analyzed from 31 randomized studies (7,215 pts) of epoetin alfa vs non-EPO (15 studies) or placebo (16 studies) in pts with CIA. A landmark analysis was used; Hb change was set at a specific time (4 and 8 weeks) and subsequent survival was examined separately for EPO and placebo. Pts were categorized as “Hb increased” (>0.5 g/dL), “Hb decreased” (>0.5 g/dL), or “Hb stable” (within ±0.5 g/dL) compared to baseline. Hb stable was compared to other Hb change categories with Cox proportional hazards models, stratified by study and adjusted for potential confounders. Results: The hazard ratio (HR) for Hb decreased versus Hb stable at 4 weeks was 1.44 for EPO (95% CI: 1.04, 1.99), indicating worse survival for pts with a decline in Hb. This association was weaker for placebo (HR: 1.12; 95% CI: 0.74, 1.67). Increased risk with declining Hb in EPO-treated pts was most pronounced in studies that maintained Hb ≥12 g/dL or treated pts for >12–16 weeks (1,876 pts). Patterns were similar using the 8-week landmark. In both EPO-treated and placebo pts, transfusion increased the rate of on-study death ∼3.5 fold (treating transfusion as a time-dependent variable). Conclusions: These exploratory findings suggest that both decreased Hb after 4 or 8 weeks of EPO treatment and transfusion are associated with increased risk of death. In spite of adjustment for other prognostic factors, it is likely that this association reflects poorer underlying prognosis of pts whose Hb fails to respond. ESAs should be discontinued in the absence of a Hb response. [Table: see text]

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