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.