Edouard L Fu1,2, Marco Trevisan2, Catherine M Clase3,4, Marie Evans5, Bengt Lindholm5, Joris I Rotmans6, Merel van Diepen7, Friedo W Dekker7, Juan-Jesus Carrero2. 1. Departments of Clinical Epidemiology and e.l.fu@lumc.nl. 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden. 3. Department of Medicine and. 4. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; and. 5. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. 6. Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. 7. Departments of Clinical Epidemiology and.
Abstract
BACKGROUND AND OBJECTIVES: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment. RESULTS: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for ≥30%. Similar graded associations were present for heart failure (2275 events, P<0.001) and ESKD (52 events; P<0.001), and, less consistently, myocardial infarction (842 events, P=0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk. CONCLUSIONS: Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes.
BACKGROUND AND OBJECTIVES: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment. RESULTS: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for ≥30%. Similar graded associations were present for heart failure (2275 events, P<0.001) and ESKD (52 events; P<0.001), and, less consistently, myocardial infarction (842 events, P=0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk. CONCLUSIONS: Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes.
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