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Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study
Morten Schmidt1,2,3, Kathryn E Mansfield4, Krishnan Bhaskaran4
1Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK morten.schmidt@clin.au.dk.
Insights
Increases in creatinine after starting angiotensin converting enzyme inhibitors or angiotensin receptor blockers are linked to adverse cardiorenal outcomes. This association exists even for increases below the 30% threshold, indicating a graduated risk relationship.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are crucial for managing cardiovascular and renal diseases.
- Monitoring creatinine levels is standard practice during ACEi/ARB therapy, with a 30% increase often triggering treatment review.
- Long-term cardiorenal outcomes associated with creatinine increases below the 30% threshold require further investigation.
Purpose of the Study:
- To investigate the association between elevated creatinine concentrations post-ACEi/ARB initiation and long-term cardiorenal outcomes.
- To determine if creatinine increases below the 30% threshold are associated with adverse events.
- To establish the relationship between the magnitude of creatinine increase and the risk of cardiorenal events.
Main Methods:
- A population-based cohort study utilizing UK electronic health records (Clinical Practice Research Datalink and Hospital Episode Statistics) from 1997-2014.
- Inclusion of 122,363 patients initiating ACEi or ARB treatment.
- Poisson regression analysis adjusted for multiple confounders to compare cardiorenal outcomes (end-stage renal disease, myocardial infarction, heart failure, death) based on creatinine increase categories.
Main Results:
- A 30% or greater increase in creatinine was observed in 1.7% of patients and was associated with significantly higher rates of end-stage renal disease (IRR 3.43), myocardial infarction (IRR 1.46), heart failure (IRR 1.37), and death (IRR 1.84).
- A graduated relationship was observed between the magnitude of creatinine increase and adverse outcomes, with all P values for trends <0.001.
- Even creatinine increases below 30% (10-19% and 20-29%) were associated with increased incidence rate ratios for all outcomes, including death.
Conclusions:
- Elevated creatinine levels following ACEi/ARB initiation are linked to adverse cardiorenal outcomes in a dose-dependent manner.
- The risk of adverse cardiorenal events exists even for creatinine increases below the 30% guideline threshold.
- These findings suggest a need to re-evaluate monitoring and management strategies for patients on ACEi/ARB therapy experiencing even modest creatinine increases.
Abstract:
Objective To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment.Design Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics.Setting UK primary care, 1997-2014.Participants Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363).Main outcome measures Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs.Results Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (<10%, 10-19%, 20-29%, 30-39%, and ≥40%) showed a graduated relation for all outcomes (all P values for trends <0.001). Notably, creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using <10% as reference). Results were consistent across calendar periods, across subgroups of patients, and among continuing users.Conclusions Increases in creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment were associated with adverse cardiorenal outcomes in a graduated relation, even below the guideline recommended threshold of a 30% increase for stopping treatment.
